TY  - JOUR
AB  - BACKGROUND: Isolated REM sleep behavior disorder (iRBD) is a prodromal stage of alpha-synucleinopathies. Biomarkers are crucial for predicting and monitoring its progression, warranting long-term neuroimaging studies. While the Parkinson's Disease Related Pattern (PDRP) from 18F-FDG PET is a recognized Parkinson's Disease (PD) biomarker, its role in tracking progression in prodromal PD remains unclear. OBJECTIVE: To explore PDRP expression across three time points using 18F-FDG PET over an 8-year follow-up in iRBD. METHODS: Thirteen iRBD subjects underwent 18F-FDG PET brain scans at baseline (BL), follow-up 1 (FU1, 4 years), and follow-up 2 (FU2, 8 years). Among them, four developed PD, one Dementia with Lewy Bodies (DLB), three showed subthreshold parkinsonism, and five showed no progression. PDRP z-scores were analyzed within and between groups (converters vs. non-converters) using a two-way repeated measures ANOVA. Similar analyses were conducted for motor scores (Unified Parkinson's Disease Rating Scale part three, UPDRS-III). RESULTS: There was a significant main effect of group (p = 0.011), time (p < 0.001), and a group*time interaction (p = 0.020), indicating that while PDRP z-scores increased over time in most iRBD subjects, the increase was more pronounced in converters (n = 5) than in non-converters (n = 8). Post-hoc tests revealed significantly higher PDRP z-scores in converters compared to non-converters at FU1 (p = 0.042) and FU2 (p = 0.024). For UPDRS-III scores we found significant effects of group (p = 0.011), time (p < 0.001), and their interaction (p = 0.0003). CONCLUSIONS: Repeated 18F-FDG PET scans may be useful to monitor prodromal disease progression and predict conversion in iRBD patients.
AU  - Carli, G.*
AU  - Dortmond, A.*
AU  - Janzen, A.*
AU  - Sittig, E.*
AU  - De Meyer, E.*
AU  - Leenders, K.L.*
AU  - Oertel, W.H.
AU  - Meles, S.K.*
C1  - 73996
C2  - 57295
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
TI  - Parkinson's Disease-Related pattern in isolated REM sleep behaviour disorder as a prodromal progression marker: 8-Year Follow-Up changes assessed at three time points.
JO  - Eur. J. Nucl. Med. Mol. Imaging
PB  - Springer
PY  - 2025
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Aim: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. Methods: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. Results: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. Conclusion: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.
AU  - Adebahr, S.*
AU  - Althaus, A.*
AU  - Scharl, S.*
AU  - Strouthos, I.*
AU  - Farolfi, A.*
AU  - Serani, F.*
AU  - Lanzafame, H.*
AU  - Trapp, C.*
AU  - Koerber, S.A.*
AU  - Peeken, J.C.
AU  - Vogel, M.M.
AU  - Vrachimis, A.*
AU  - Spohn, S.K.B.*
AU  - Grosu, A.L.*
AU  - Kroeze, S.G.C.*
AU  - Guckenberger, M.*
AU  - Fanti, S.*
AU  - Hruby, G.*
AU  - Emmett, L.*
AU  - Belka, C.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Henkenberens, C.*
AU  - Aebersold, D.M.*
AU  - Wiegel, T.*
AU  - Afshar-Oromieh, A.*
AU  - Zamboglou, C.*
AU  - Shelan, M.*
C1  - 68246
C2  - 54771
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 558-567
TI  - The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 51
IS  - 2
PB  - Springer
PY  - 2024
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose: Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with 18F-FDG PET in iRBD is promising, but longitudinal studies are scarce. We investigated the regional brain changes in iRBD over time, related to phenoconversion. Methods: Twenty iRBD patients underwent two consecutive 18F-FDG PET brain scans and clinical assessments (3.7 ± 0.6 years apart). Seventeen patients also underwent 123I-MIBG and 123I-FP-CIT SPECT scans at baseline. Four subjects phenoconverted to Parkinson’s disease (PD) during follow-up. 18F-FDG PET scans were compared to controls with a voxel-wise single-subject procedure. The relationship between regional brain changes in metabolism and PD-related pattern scores (PDRP) was investigated. Results: Individual hypometabolism t-maps revealed three scenarios: (1) normal 18F-FDG PET scans at baseline and follow-up (N = 10); (2) normal scans at baseline but occipital or occipito-parietal hypometabolism at follow-up (N = 4); (3) occipital hypometabolism at baseline and follow-up (N = 6). All patients in the last group had pathological 123I-MIBG and 123I-FP-CIT SPECT. iRBD converters (N = 4) showed occipital hypometabolism at baseline (third scenario). At the group level, hypometabolism in the frontal and occipito-parietal regions and hypermetabolism in the cerebellum and limbic regions were progressive over time. PDRP z-scores increased over time (0.54 ± 0.36 per year). PDRP expression was driven by occipital hypometabolism and cerebellar hypermetabolism. Conclusions: Our results suggest that occipital hypometabolism at baseline in iRBD implies a short-term conversion to PD. This might help in stratification strategies for disease-modifying trials.
AU  - Carli, G.*
AU  - Meles, S.K.*
AU  - Janzen, A.*
AU  - Sittig, E.*
AU  - Kogan, R.V.*
AU  - Perani, D.*
AU  - Oertel, W.H.
AU  - Leenders, K.L.*
C1  - 68479
C2  - 54701
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 3290-3301
TI  - Occipital hypometabolism is a risk factor for conversion to Parkinson’s disease in isolated REM sleep behaviour disorder.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 11
PB  - Springer
PY  - 2023
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment. METHODS: Eight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40-45 mm was employed to match the signal-to-noise ratio of 225Ac and 177Lu, respectively. RESULTS: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. CONCLUSION: Quantitative low-count SPECT imaging of the peak at 440 keV during [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys.
AU  - Delker, A.*
AU  - Schleske, M.*
AU  - Liubchenko, G.*
AU  - Berg, I.*
AU  - Zacherl, M.J.*
AU  - Brendel, M.*
AU  - Gildehaus, F.J.*
AU  - Rumiantcev, M.*
AU  - Resch, S.*
AU  - Hürkamp, K.
AU  - Wenter, V.*
AU  - Unterrainer, L.M.*
AU  - Bartenstein, P.*
AU  - Ziegler, S.I.*
AU  - Beyer, L.*
AU  - Böning, G.*
C1  - 67216
C2  - 54227
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 1280-1290
TI  - Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 5
PB  - Springer
PY  - 2023
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Patient-tailored management of thyroid nodules requires improved risk of malignancy stratification by accurate preoperative nodule assessment, aiming to personalize decisions concerning diagnostics and treatment. Here, we perform an exploratory pilot study to identify possible patterns on multispectral optoacoustic tomography (MSOT) for thyroid malignancy stratification. For the first time, we directly correlate MSOT images with histopathology data on a detailed level. METHODS: We use recently enhanced data processing and image reconstruction methods for MSOT to provide next-level image quality by means of improved spatial resolution and spectral contrast. We examine optoacoustic features in thyroid nodules associated with vascular patterns and correlate these directly with reference histopathology. RESULTS: Our methods show the ability to resolve blood vessels with diameters of 250 μm at depths of up to 2 cm. The vessel diameters derived on MSOT showed an excellent correlation (R2-score of 0.9426) with the vessel diameters on histopathology. Subsequently, we identify features of malignancy observable in MSOT, such as intranodular microvascularity and extrathyroidal extension verified by histopathology. Despite these promising features in selected patients, we could not determine statistically relevant differences between benign and malignant thyroid nodules based on mean oxygen saturation in thyroid nodules. Thus, we illustrate general imaging artifacts of the whole field of optoacoustic imaging that reduce image fidelity and distort spectral contrast, which impedes quantification of chromophore presence based on mean concentrations. CONCLUSION: We recommend examining optoacoustic features in addition to chromophore quantification to rank malignancy risk. We present optoacoustic images of thyroid nodules with the highest spatial resolution and spectral contrast to date, directly correlated to histopathology, pushing the clinical translation of MSOT.
AU  - Noltes, M.E.*
AU  - Bader, M.
AU  - Metman, M.J.H.*
AU  - Vonk, J.*
AU  - Steinkamp, P.J.*
AU  - Kukacka, J.
AU  - Westerlaan, H.E.*
AU  - Dierckx, R.A.J.O.*
AU  - van Hemel, B.M.*
AU  - Brouwers, A.H.*
AU  - van Dam, G.M.*
AU  - Jüstel, D.
AU  - Ntziachristos, V.
AU  - Kruijff, S.*
C1  - 67616
C2  - 53923
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2736-2750
TI  - Towards in vivo characterization of thyroid nodules suspicious for malignancy using multispectral optoacoustic tomography.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 9
PB  - Springer
PY  - 2023
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS: The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS: The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION: This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field.
AU  - Solomonidou, N.*
AU  - Germanou, D.*
AU  - Strouthos, I.*
AU  - Karagiannis, E.*
AU  - Farolfi, A.*
AU  - Koerber, S.A.*
AU  - Debus, J.*
AU  - Peeken, J.C.
AU  - Vogel, M.M.
AU  - Vrachimis, A.*
AU  - Spohn, S.K.B.*
AU  - Shelan, M.*
AU  - Aebersold, D.*
AU  - Grosu, A.L.*
AU  - Ceci, F.*
AU  - Kroeze, S.G.C.*
AU  - Guckenberger, M.*
AU  - Fanti, S.*
AU  - Belka, C.*
AU  - Hruby, G.*
AU  - Scharl, S.*
AU  - Wiegel, T.*
AU  - Bartenstein, P.*
AU  - Henkenberens, C.*
AU  - Emmett, L.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Ferentinos, K.*
AU  - Zamboglou, C.*
C1  - 67735
C2  - 54043
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2529-2536
TI  - PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 8
PB  - Springer
PY  - 2023
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.
AU  - Spohn, S.K.B.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Ruf, J.*
AU  - Mix, M.*
AU  - Benndorf, M.*
AU  - Bamberg, F.*
AU  - Makowski, M.R.*
AU  - Kirste, S.*
AU  - Ruhle, A.*
AU  - Nouvel, J.*
AU  - Sprave, T.*
AU  - Vogel, M.M.E.*
AU  - Galitsnaya, P.*
AU  - Gschwend, J.E.*
AU  - Gratzke, C.*
AU  - Stief, C.*
AU  - Löck, S.*
AU  - Zwanenburg, A.*
AU  - Trapp, C.*
AU  - Bernhardt, D.*
AU  - Nekolla, S.G.*
AU  - Li, M.*
AU  - Belka, C.*
AU  - Combs, S.E.
AU  - Eiber, M.*
AU  - Unterrainer, L.*
AU  - Unterrainer, M.*
AU  - Bartenstein, P.*
AU  - Grosu, A.L.*
AU  - Zamboglou, C.*
AU  - Peeken, J.C.
C1  - 67718
C2  - 54026
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2537-2547
TI  - Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 8
PB  - Springer
PY  - 2023
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer’s disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results: In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions: This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer’s disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors.
AU  - Barbone, G.E.*
AU  - Bravin, A.*
AU  - Mittone, A.*
AU  - Pacureanu, A.*
AU  - Mascio, G.*
AU  - Di Pietro, P.*
AU  - Kraiger, M.
AU  - Eckermann, M.*
AU  - Romano, M.*
AU  - Hrabě de Angelis, M.
AU  - Cloetens, P.*
AU  - Bruno, V.*
AU  - Battaglia, G.*
AU  - Coan, P.*
C1  - 65777
C2  - 52477
SP  - 4338-4357
TI  - X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer’s disease.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 49
IS  - 13
PY  - 2022
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Deep learning is an emerging reconstruction method for positron emission tomography (PET), which can tackle complex PET corrections in an integrated procedure. This paper optimizes the direct PET reconstruction from sinogram on a long axial field of view (LAFOV) PET. METHODS: This paper proposes a novel deep learning architecture to reduce the biases during direct reconstruction from sinograms to images. This architecture is based on an encoder-decoder network, where the perceptual loss is used with pre-trained convolutional layers. It is trained and tested on data of 80 patients acquired from recent Siemens Biograph Vision Quadra long axial FOV (LAFOV) PET/CT. The patients are randomly split into a training dataset of 60 patients, a validation dataset of 10 patients, and a test dataset of 10 patients. The 3D sinograms are converted into 2D sinogram slices and used as input to the network. In addition, the vendor reconstructed images are considered as ground truths. Finally, the proposed method is compared with DeepPET, a benchmark deep learning method for PET reconstruction. RESULTS: Compared with DeepPET, the proposed network significantly reduces the root-mean-squared error (NRMSE) from 0.63 to 0.6 (p < 0.01) and increases the structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) from 0.93 to 0.95 (p < 0.01) and from 82.02 to 82.36 (p < 0.01), respectively. The reconstruction time is approximately 10 s per patient, which is shortened by 23 times compared with the conventional method. The errors of mean standardized uptake values (SUVmean) for lesions between ground truth and the predicted result are reduced from 33.5 to 18.7% (p = 0.03). In addition, the error of max SUV is reduced from 32.7 to 21.8% (p = 0.02). CONCLUSION: The results demonstrate the feasibility of using deep learning to reconstruct images with acceptable image quality and short reconstruction time. It is shown that the proposed method can improve the quality of deep learning-based reconstructed images without additional CT images for attenuation and scattering corrections. This study demonstrated the feasibility of deep learning to rapidly reconstruct images without additional CT images for complex corrections from actual clinical measurements on LAFOV PET. Despite improving the current development, AI-based reconstruction does not work appropriately for untrained scenarios due to limited extrapolation capability and cannot completely replace conventional reconstruction currently.
AU  - Ma, R.
AU  - Hu, J.*
AU  - Sari, H.*
AU  - Xue, S.*
AU  - Mingels, C.*
AU  - Viscione, M.*
AU  - Kandarpa, V.S.S.*
AU  - Li, W.B.
AU  - Visvikis, D.*
AU  - Qiu, R.*
AU  - Rominger, A.*
AU  - Li, J.*
AU  - Shi, K.*
C1  - 65641
C2  - 52541
SP  - 4464-4477
TI  - An encoder-decoder network for direct image reconstruction on sinograms of a long axial field of view PET.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 49
IS  - 13
PY  - 2022
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. METHODS: Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. RESULTS: Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results. CONCLUSION: The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary.
AU  - Spohn, S.K.B.*
AU  - Farolfi, A.*
AU  - Schandeler, S.*
AU  - Vogel, M.M.E.*
AU  - Ruf, J.*
AU  - Mix, M.*
AU  - Kirste, S.*
AU  - Ceci, F.*
AU  - Fanti, S.*
AU  - Lanzafame, H.*
AU  - Serani, F.*
AU  - Gratzke, C.*
AU  - Sigle, A.*
AU  - Combs, S.E.
AU  - Bernhardt, D.*
AU  - Gschwend, J.E.*
AU  - Buchner, J.A.*
AU  - Trapp, C.*
AU  - Belka, C.*
AU  - Bartenstein, P.*
AU  - Unterrainer, L.*
AU  - Unterrainer, M.*
AU  - Eiber, M.*
AU  - Nekolla, S.G.*
AU  - Schiller, K.*
AU  - Grosu, A.L.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Zamboglou, C.*
AU  - Peeken, J.C.
C1  - 66007
C2  - 53039
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 218-227
TI  - The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 50
IS  - 1
PB  - Springer
PY  - 2022
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett's esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. METHODS: Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. RESULTS: Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized  by human BE dysplastic patient-derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. CONCLUSION: In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.
AU  - Fang, H.Y.*
AU  - Stangl, S.*
AU  - Marcazzan, S.
AU  - Carvalho, M.J.B.*
AU  - Baumeister, T.*
AU  - Anand, A.*
AU  - Strangmann, J.*
AU  - Huspenina, J.S.*
AU  - Wang, T.C.*
AU  - Schmid, R.M.*
AU  - Feith, M.*
AU  - Friess, H.*
AU  - Ntziachristos, V.
AU  - Multhoff, G.*
AU  - Gorpas, D.
AU  - Quante, M.*
C1  - 63797
C2  - 51626
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
TI  - Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.
JO  - Eur. J. Nucl. Med. Mol. Imaging
PB  - Springer
PY  - 2021
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.
AU  - Paprottka, K.J.*
AU  - Kleiner, S.*
AU  - Preibisch, C.*
AU  - Kofler, F.*
AU  - Schmidt-Graf, F.*
AU  - Delbridge, C.*
AU  - Bernhardt, D.
AU  - Combs, S.E.
AU  - Gempt, J.*
AU  - Meyer, B.*
AU  - Zimmer, C.*
AU  - Menze, B.H.*
AU  - Yakushev, I.*
AU  - Kirschke, J.S.*
AU  - Wiestler, B.*
C1  - 62458
C2  - 50883
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 4445-4455
TI  - Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 48
IS  - 13
PB  - Springer
PY  - 2021
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During treatment planning, the definition of the target volume remains challenging using MR and CT imaging alone. This is the first study to analyze the impact of additional PET-imaging on local control (LC) and overall survival (OS) after high-precision RT. Methods We analyzed 339 meningiomas treated between 2000 and 2018. For analyses, we divided the patients in low-grade (n = 276) and high-grade (n = 63) cases. We performed RT in an adjuvant setting due to subtotal resection or later due to recurrent tumor growth. The target volumes were delineated based on diagnostic CT and MRI and, if available, additional PET-imaging (low-grade: n = 164, 59.4%; high-grade: n = 39, 61.9%) with either Ga-68-Dotanoc/Dotatoc, F-18-fluoroethyltyrosine or C-11-methionine tracer. Patients were treated with fractionated stereotactic RT with a median total dose and dose per fraction of 54 Gy and 1.8 Gy, respectively. Results Median follow-up was 5.6 years. For low-grade meningiomas, mean OS was 15.6 years and mean LC was 16.9 years; for high-grade cases mean OS was 11.6 years, and mean LC was 11.1 years. In univariate analyses, PET-imaging had a significant impact on OS (p = 0.035) and LC (p = 0.041) for low-grade meningiomas and remained significant (p = 0.015) for LC in the multivariate analysis. For high-grade cases, PET did not influence both OS and LC. Further prognostic factors could be identified. Conclusions For low-grade meningiomas, we showed that the addition of PET-imaging for target volume definition led to a significantly enhanced LC. Thus, PET improves the detection of tumor cells and helps distinguish between healthy tissue and meningioma tissue, especially during the treatment planning process.
AU  - Kessel, K.A.
AU  - Weber, W.*
AU  - Yakushev, I.*
AU  - Fischer, H.*
AU  - Voglhuber, T.*
AU  - Diehl, C.*
AU  - Straube, C.*
AU  - Zimmer, C.*
AU  - Wiestler, B.*
AU  - Gempt, J.*
AU  - Meyer, B.*
AU  - Combs, S.E.
C1  - 57399
C2  - 47759
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - 1391-1399
TI  - Integration of PET-imaging into radiotherapy treatment planning for low-grade meningiomas improves outcome.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 47
IS  - 6
PB  - Springer
PY  - 2020
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs). Methods Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling. Results Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node-specific decision curve analysis, there was a clinical net benefit above LN short diameter. Conclusion The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.
AU  - Peeken, J.C.
AU  - Shouman, M.A.*
AU  - Kroenke, M.*
AU  - Rauscher, I.*
AU  - Maurer, T.*
AU  - Gschwend, J.E.*
AU  - Eiber, M.*
AU  - Combs, S.E.
C1  - 59240
C2  - 48684
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2968-2977
TI  - A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 47
IS  - 13
PB  - Springer
PY  - 2020
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose: Approximately 40–70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases’ site on outcome after metastasis-directed radiotherapy (MDR). Methods: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. Results: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04–47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03–18.30). After a median follow-up of 16 months (1–57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. Conclusion: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.
AU  - Schmidt-Hegemann, N.S.*
AU  - Kroeze, S.G.C.*
AU  - Henkenberens, C.*
AU  - Vogel, M.M.
AU  - Kirste, S.*
AU  - Becker, J.*
AU  - Burger, I.A.*
AU  - Derlin, T.*
AU  - Bartenstein, P.*
AU  - Eiber, M.*
AU  - Mix, M.*
AU  - la Fougère, C.*
AU  - Müller, A.C.*
AU  - Grosu, A.-L.*
AU  - Combs, S.E.
AU  - Christiansen, H.*
AU  - Guckenberger, M.*
AU  - Belka, C.*
C1  - 58786
C2  - 48321
SP  - 1852-1863
TI  - Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy—a multicenter retrospective study.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 47
IS  - 8
PY  - 2020
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose: Since the success of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging for patients with oligorecurrent prostate cancer (ORPC), it is increasingly used for radiotherapy as metastasis-directed therapy (MDT). Therefore, we developed a prognostic risk classification for biochemical relapse-free survival (bRFS) for patients after PSMA-PET-guided MDT after radical prostatectomy. Methods: We analyzed 292 patients with local recurrence (LR) and/or pelvic lymph node (LN) lesions and/or up to five distant LN, bone (BM), or visceral metastases (VM) detected with [68Ga]PSMA-PET imaging. Median follow-up was 16 months (range 0–57). The primary endpoint was bRFS after MDT. Cox regression analysis for risk factors was incorporated into a recursive partitioning analysis (RPA) with classification and regression tree method. Results: PSA at recurrence ≥ 0.8 ng/mL, BM, and VM was significantly associated with biochemical relapse. RPA showed five groups with tenfold cross-validation of 0.294 (SE 0.032). After building risk classes I to IV (p < 0.0001), mean bRFS was 36.3 months (95% CI 32.4–40.1) in class I (PSA < 0.8 ng/mL, no BM) and 25.8 months (95% CI 22.5–29.1) in class II (PSA ≥ 0.8 ng/mL, no BM, no VM). LR and/or pelvic LNs caused relapse in classes I and II. Mean bRFS was 16.0 months (95% CI 12.4–19.6) in class III (PSA irrelevant, present BM) and 5.7 months (95% CI 2.7–8.7) in class IV (PSA ≥ 0.8 ng/mL, no BM, present VM). Conclusion: We developed and internally validated a risk classification for bRFS after PSMA-PET-guided MDT. Patients with PSA < 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) had the most promising bRFS. PSA ≥ 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) indicated intermediate risk for failure. Patients with BM were at higher risk regardless of the PSA. However, those patients still show satisfactory bRFS. In patients with VM, bRFS is heavily decreased. MDT in such cases should be discussed individually.
AU  - Vogel, M.M.
AU  - Kroeze, S.G.C.*
AU  - Henkenberens, C.*
AU  - Schmidt-Hegemann, N.S.*
AU  - Kirste, S.*
AU  - Becker, J.*
AU  - Burger, I.A.*
AU  - Derlin, T.*
AU  - Bartenstein, P.*
AU  - Mix, M.*
AU  - la Fougère, C.*
AU  - Eiber, M.*
AU  - Christiansen, H.*
AU  - Belka, C.*
AU  - Grosu, A.-L.*
AU  - Müller, A.C.*
AU  - Guckenberger, M.*
AU  - Combs, S.E.
C1  - 58612
C2  - 48302
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2328-2338
TI  - Prognostic risk classification for biochemical relapse-free survival in patients with oligorecurrent prostate cancer after [68Ga]PSMA-PET-guided metastasis-directed therapy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 47
IS  - 10
PB  - Springer
PY  - 2020
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Laitinen, I.*
AU  - Jones, S.*
AU  - Derdau, V.*
AU  - Eriksson, O.*
AU  - Haack, T.B.*
AU  - Johansson, L.*
AU  - Larsen, P.*
AU  - Loewe, C.*
AU  - Pierrou, S.*
AU  - Plettenburg, O.
AU  - Schudok, M.*
AU  - Velikyan, I.*
AU  - Wagner, M.*
C1  - 57381
C2  - 47714
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S707-S708
TI  - Assessment of in vivo glucagon receptor engagement in rat liver.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 46
IS  - SUPPL 1
PB  - Springer
PY  - 2019
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Bolch, W.E.*
AU  - Lee, C.*
AU  - Zankl, M.
AU  - Jokisch, D.W.*
AU  - Petoussi-Henß, N.
AU  - Kim, C.*
AU  - Hunt, J.*
AU  - Sato, T.*
AU  - Eckerman, K.F.*
AU  - Kim, K.*
AU  - Li, J.*
AU  - Schlattl, H.
AU  - Yeom, Y.S.*
AU  - Wayson, M.*
AU  - Pafundi, D.*
AU  - Stepusin, E.*
C1  - 54813
C2  - 45875
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S79-S79
TI  - The ICRP reference pediatric phantoms - design, construction, and applications to nuclear medicine dosimetry.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 45
PB  - Springer
PY  - 2018
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Höllriegl, V.
AU  - Li, W.B.
C1  - 54812
C2  - 45877
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S242-S242
TI  - Application of new ICRP biokinetic models for pharmacokinetic modelling of Radium-223 used for treatment of prostate cancer.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 45
PB  - Springer
PY  - 2018
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Karimi Ghodoosi, E.
AU  - D'Alessandria, C.*
AU  - Eiber, M.*
AU  - Li, W.B.
AU  - Navab, N.*
AU  - Ziegler, S.*
C1  - 54811
C2  - 45878
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S112-S113
TI  - Comparison of absorbed dose to kidneys using quantitative SPECT/CT and whole body planar images for Lu-177-PSMA I&T in prostate cancer therapy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 45
PB  - Springer
PY  - 2018
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Li, W.B.
AU  - Zhernosekov, K.*
AU  - Höllriegl, V.
AU  - Meckel, M.*
AU  - Ziegler, S.*
AU  - Konijnenberg, M.W.*
AU  - Shi, K.*
C1  - 54810
C2  - 45879
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S125-S125
TI  - Feasibility study of applying ICRP biokinetic models for pharmacokinetic modelling of alpha-emitter thorium-227 used in targeted radionuclide therapy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 45
PB  - Springer
PY  - 2018
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Ma, R.*
AU  - Qiu, R.*
AU  - Li, W.B.
AU  - Li, J.*
C1  - 54814
C2  - 45876
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S359-S359
TI  - Patient specific internal dose estimation based on quantitative SPECTCT imaging.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 45
PB  - Springer
PY  - 2018
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Background: Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. Objective: In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. Methods and materials: Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a “blind” radiation therapy after RPE and LAE. Results: Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68Ga-PSMA-PET imaging. Conclusion: Compared to conventional CT or MRI staging, 68Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.
AU  - Schiller, K.*
AU  - Sauter, K.*
AU  - Dewes, S.*
AU  - Eiber, M.*
AU  - Maurer, T.*
AU  - Gschwend, J.E.*
AU  - Combs, S.E.
AU  - Habl, G.
C1  - 51455
C2  - 43222
CY  - New York
SP  - 1656–1662
TI  - Patterns of failure after radical prostatectomy in prostate cancer – implications for radiation therapy planning after 68Ga-PSMA-PET imaging.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 44
IS  - 10
PB  - Springer
PY  - 2017
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Purpose: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. Methods: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. Results: There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. Conclusion: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.
AU  - Handkiewicz-Junak, D.*
AU  - Swierniak, M.*
AU  - Rusinek, D.*
AU  - Oczko-Wojciechowska, M.*
AU  - Dom, G.*
AU  - Maenhaut, C.*
AU  - Unger, K.
AU  - Detours, V.*
AU  - Bogdanova, T.*
AU  - Thomas, G.*
AU  - Likhtarov, I.*
AU  - Jaksik, R.*
AU  - Kowalski, M.*
AU  - Chmielik, E.*
AU  - Jarzab, M.*
AU  - Swierniak, A.*
AU  - Jarzab, B.*
C1  - 47790
C2  - 39526
SP  - 1267-1277
TI  - Gene signature of the post-Chernobyl papillary thyroid cancer.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 43
IS  - 7
PY  - 2016
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Molecular optical imaging using monoclonal antibodies is slow with low tumour to background ratio. We used anti-HER2 VHHs conjugated to IRDye 800CW to investigate their potential as probes for rapid optical molecular imaging of HER2-positive tumours by the determination of tumour accumulation and tumour to background levels. METHODS: Three anti-HER2 VHHs (11A4, 18C3, 22G12) were selected with phage display and produced in Escherichia coli. Binding affinities of these probes to SKBR3 cells were determined before and after site-specific conjugation to IRDye 800CW. To determine the potential of VHH-IR as imaging probes, serial optical imaging studies were carried out using human SKBR3 and human MDA-MB-231 xenograft breast cancer models. Performance of the anti-HER2 VHH-IR was compared to that of trastuzumab-IR and a non-HER2-specific VHH-IR. Image-guided surgery was performed during which SKBR3 tumour was removed under the guidance of the VHH-IR signal. RESULTS: Site-specific conjugation of IRDye 800CW to three anti-HER2 VHHs preserved high affinity binding with the following dissociation constants (KD): 11A4 1.9 ± 0.03, 18C3 14.3 ± 1.8 and 22G12 3.2 ± 0.5 nM. Based upon different criteria such as binding, production yield and tumour accumulation, 11A4 was selected for further studies. Comparison of 11A4-IR with trastuzumab-IR showed ∼20 times faster tumour accumulation of the anti-HER2 VHH, with a much higher contrast between tumour and background tissue (11A4-IR 2.5 ± 0.3, trastuzumab-IR 1.4 ± 0.4, 4 h post-injection). 11A4-IR was demonstrated to be a useful tool in image-guided surgery. CONCLUSION: VHH-IR led to a much faster tumour accumulation with high tumour to background ratios as compared to trastuzumab-IR allowing same-day imaging for clinical investigation as well as image-guided surgery.
AU  - Kijanka, M.*
AU  - Warnders, F.-J.*
AU  - El Khattabi, M.*
AU  - Lub-de Hooge, M.*
AU  - van Dam, G.M.*
AU  - Ntziachristos, V.
AU  - de Vries, L.*
AU  - Oliveira, S.*
AU  - van Bergen en Henegouwen, P.M.*
C1  - 26001
C2  - 32016
SP  - 1718-1729
TI  - Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 40
IS  - 11
PB  - Springer
PY  - 2013
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Targeted delivery of alpha-particle-emitting radionuclides is a promising novel option in cancer therapy. We generated stable conjugates of the vascular tumour-homing peptide F3 both with (225)Ac and (213)Bi that specifically bind to nucleolin on the surface of proliferating tumour cells. The aim of our study was to determine the therapeutic efficacy of (225)Ac-DOTA-F3 in comparison with that of (213)Bi-DTPA-F3. METHODS: ID(50) values of (213)Bi-DTPA-F3 and (225)Ac-DOTA-F3 were determined via clonogenic assays. The therapeutic efficacy of both constructs was assayed by repeated treatment of mice bearing intraperitoneal MDA-MB-435 xenograft tumours. Therapy was monitored by bioluminescence imaging. Nephrotoxic effects were analysed by histology. RESULTS: ID(50) values of (213)Bi-DTPA-F3 and (225)Ac-DOTA-F3 were 53 kBq/ml and 67 Bq/ml, respectively. The median survival of control mice treated with phosphate-buffered saline was 60 days after intraperitoneal inoculation of 1 × 10(7) MDA-MB-435 cells. Therapy with 6 × 1.85 kBq of (225)Ac-DOTA-F3 or 6 × 1.85 MBq of (213)Bi-DTPA-F3 prolonged median survival to 95 days and 97 days, respectively. While F3 labelled with short-lived (213)Bi (t (1/2) 46 min) reduced the tumour mass at early time-points up to 30 days after treatment, the antitumour effect of (225)Ac-DOTA-F3 (t (1/2) 10 days) increased at later time-points. The difference in the fraction of necrotic cells after treatment with (225)Ac-DOTA-F3 (43%) and with (213)Bi-DTPA-F3 (36%) was not significant. Though histological analysis of kidney samples revealed acute tubular necrosis and tubular oedema in 10-30% of animals after treatment with (225)Ac-DOTA-F3 or (213)Bi-DTPA-F3, protein casts were negligible (2%), indicating only minor damage to the kidney. CONCLUSION: Therapy with both (225)Ac-DOTA-F3 and (213)Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both constructs favours future therapeutic application.
AU  - Essler, M.*
AU  - Gärtner, F.C.*
AU  - Neff, F.
AU  - Blechert, B.*
AU  - Senekowitsch-Schmidtke, R.*
AU  - Bruchertseifer, F.*
AU  - Morgenstern, A.*
AU  - Seidl, C..*
C1  - 7382
C2  - 29688
SP  - 602-612
TI  - Therapeutic efficacy and toxicity of 225Ac-labelled vs. 213Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 39
IS  - 4
PB  - Springer
PY  - 2012
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Positron emission tomography (PET) with the thymidine analogue [(18)F]fluorothymidine ([(18)F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [(18)F]FLT to the glucose analogue [(18)F]fluorodeoxyglucose ([(18)F]FDG) regarding dose-dependent visualization and prediction of early therapy response. METHODS: Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [(18)F]FLT and [(18)F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [(18)F]FLT and [(18)F]FDG uptake 48 h later. RESULTS: In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 μg to 200 μg. The mean tumour-to-background ratio (TBR) of [(18)F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [(18)F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [(18)F]FLT uptake, in contrast to a variable and decelerated reduction in [(18)F]FDG uptake. Thus, the increase in [(18)F]FDG uptake in vivo presumably reflected nonspecific glucose metabolism of inflammatory cells, as confirmed by histology of explanted lymphomas. CONCLUSION: Early responses to dose-dependent antiproliferative treatment in high-grade lymphoma are more accurately visualized with [(18)F]FLT PET than with [(18)F]FDG PET.
AU  - Graf, N.*
AU  - Herrmann, K.*
AU  - Numberger, B.*
AU  - Zwisler, D.*
AU  - Aichler, M.
AU  - Feuchtinger, A.
AU  - Schuster, T.*
AU  - Wester, H.-J.*
AU  - Senekowitsch-Schmidtke, R.*
AU  - Peschel, C.*
AU  - Schwaiger, M.*
AU  - Keller, U.*
AU  - Dechow, T.*
AU  - Buck, A.K.*
C1  - 10953
C2  - 30455
SP  - 34-43
TI  - [18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 40
IS  - 1
PB  - Springer
PY  - 2012
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter (213)Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined (213)Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either (213)Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. METHODS: Cytotoxicity of treatment with (213)Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. RESULTS: Treatment of OVCAR-3 cells in vitro with combined (213)Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either (213)Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with (213)Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with (213)Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either (213)Bi-DTPA-F3 or paclitaxel alone. CONCLUSION: Combined treatment with (213)Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application.
AU  - Vallon, M.*
AU  - Seidl, C.*
AU  - Blechert, B.*
AU  - Li, Z.*
AU  - Gilbertz, K.P.*
AU  - Baumgart, A.*
AU  - Aichler, M.
AU  - Feuchtinger, A.
AU  - Gaertner, F.C.*
AU  - Bruchertseifer, F.*
AU  - Morgenstern, A.*
AU  - Walch, A.K.
AU  - Senekowitsch-Schmidtke, R.*
AU  - Essler, M.*
C1  - 8449
C2  - 30123
SP  - 1886-1897
TI  - Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 39
IS  - 12
PB  - Springer
PY  - 2012
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE: This article reviews and discusses different options for visualizing the microarchitecture of vessels ex vivo and in vivo with respect to reliability, practicability and availability. RESULTS AND DISCUSSION: The investigation of angiogenesis by standard histological methods, like microvessel density counts, is limited since the three-dimensional (3-D) architecture and the functionality of vessels cannot be considered properly. Coregistration of immunostained images of vessels may be performed but is time consuming and often not sufficiently accurate. Confocal fluorescence microscopy is an alternative, but only enables 3-D stacks of less than 500 nm in thickness. Multiphoton microscopy and other advanced technologies, such as optical coherence tomography and optical frequency domain imaging, provide a deeper view into tissues and allow for in vivo imaging of microvessels, which is a precondition for longitudinal studies. Besides these microscopic techniques, the vascularization in larger tissue samples can be investigated using corrosion casts in combination with scanning electron microscopy, or microcomputed tomography (microCT). Furthermore, recent improvements in microCT technology open up new perspectives for in vivo scans with high resolution and tolerable X-ray doses. Also 3-D contrast-enhanced high-frequency ultrasound has been shown to be sensitive for angiogenic vessels and even distinguishing between mature and immature vessels appears feasible. Microvessel architecture can also be visualized by MRI. Here, T1-weighted angiography techniques after injection of blood pool contrast agents appear preferable. Optoacoustic tomographic imaging has more recently shown promise for high-resolution in vivo mapping of the microvasculature in rodents using intrinsic haemoglobin-based contrast and exogenous contrast agents.
AU  - Kiessling, F.*
AU  - Razansky, D.
AU  - Alves, F.*
C1  - 953
C2  - 27391
SP  - S4-S19
TI  - Anatomical and microstructural imaging of angiogenesis.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 37
PB  - Springer
PY  - 2010
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - PURPOSE:
      	
      		Radioimmunotherapy with alpha-particle-emitting nuclides, such as 213Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213Bi-immunoconjugates.
      	
      		METHODS:
      	
      		Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213Bi-d9MAb targeting d9-E-cadherin and 213Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213Bi-d9MAb was analysed via Western blotting.
      	
      		RESULTS:
      	
      		Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of alpha-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213Bi-d9MAb compared with unspecific 213Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213Bi-immunoconjugates per cell exceeded 2 x 10(4), most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway.
      	
      		CONCLUSION:
      	
      		213Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells.
      
      
      	 
AU  - Seidl, C.*
AU  - Schröck, H.*
AU  - Seidenschwang, S.*
AU  - Beck, R.*
AU  - Schmid, E.
AU  - Abend, M.*
AU  - Becker, K.-F.
AU  - Apostolidis, C.*
AU  - Nikula, T.K.*
AU  - Kremmer, E.
AU  - Schwaiger, M.*
C1  - 3356
C2  - 22637
SP  - 274-285
TI  - Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 32
PY  - 2005
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - The purpose of this study was to assess the feasibility of use of gadophrin-2 to trace intravenously injected human hematopoietic cells in athymic mice, employing magnetic resonance (MR) imaging, optical imaging (OI), and fluorescence microscopy. Mononuclear peripheral blood cells from GCSF-primed patients were labeled with gadophrin-2 (Schering AG, Berlin, Germany), a paramagnetic and fluorescent metalloporphyrin, using established transfection techniques with cationic liposomes. The labeled cells were evaluated in vitro with electron microscopy and inductively coupled plasma atomic emission spectrometry. Then, 1×106–3×108 labeled cells were injected into 14 nude Balb/c mice and the in vivo cell distribution was evaluated with MR imaging and OI before and 4, 24, and 48 h after intravenous injection (p.i.). Five additional mice served as controls: three mice were untreated controls and two mice were investigated after injection of unlabeled cells. The contrast agent effect was determined quantitatively for MR imaging by calculating signal-to-noise-ratio (SNR) data. After completion of in vivo imaging studies, fluorescence microscopy of excised organs was performed. Intracellular cytoplasmatic uptake of gadophrin-2 was confirmed by electron microscopy. Spectrometry determined an uptake of 31.56 nmol Gd per 106 cells. After intravenous injection, the distribution of gadophrin-2 labeled cells in nude mice could be visualized by MR, OI, and fluorescence microscopy. At 4 h p.i., the transplanted cells mainly distributed to lung, liver, and spleen, and 24 h p.i. they also distributed to the bone marrow. Fluorescence microscopy confirmed the distribution of gadophrin-2 labeled cells to these target organs. Gadophrin-2 is suited as a bifunctional contrast agent for MR imaging, OI, and fluorescence microscopy and may be used to combine the advantages of each individual imaging modality for in vivo tracking of intravenously injected hematopoietic cells.
AU  - Daldrup-Link, H.E.*
AU  - Rudelius, M.*
AU  - Metz, S.*
AU  - Piontek, G.*
AU  - Pichler, B.*
AU  - Settles, M.*
AU  - Heinzmann, U.
AU  - Schlegel, J.*
AU  - Oostendorp, R.A.J.*
AU  - Rummeny, E.J.*
C1  - 2833
C2  - 22843
SP  - 1312-1321
TI  - Cell tracking with gadophrin-2: A biofunctional contrast agent for MR imaging, optical imaging and fluorescence microscopy.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 31
IS  - 9
PY  - 2004
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - The aim of this study was to use a new system of realistic voxel phantoms, based on computed tomography scanning of humans, to assess its ability to specify the internal dosimetry of selected human examples in comparison with the well-established MIRD system of mathematical anthropomorphic phantoms. Differences in specific absorbed fractions between the two systems were inferred by using organ dose estimates as the end point for comparison. A "family" of voxel phantoms, comprising an 8-week-old baby, a 7-year-old child and a 38-year-old adult, was used and a close match to these was made by interpolating between organ doses estimated for pairs of the series of six MIRD phantoms. Using both systems, doses were calculated for up to 22 organs for four radiopharmaceuticals with widely differing biodistribution and emission characteristics (technetium-99m pertechnetate, administered without thyroid blocking; iodine-123 iodide; indium-111 antimyosin; oxygen-15 water). Organ dose estimates under the MIRD system were derived using the software MIRDOSE 3, which incorporates specific absorbed fraction (SAF) values for the MIRD phantom series. The voxel system uses software based on the same dose calculation formula in conjunction with SAF values determined by Monte Carlo analysis at the GSF of the three voxel phantoms. Effective doses were also compared. Substantial differences in organ weights were observed between the two systems, 18% differing by more than a factor of 2. Out of a total of 238 organ dose comparisons, 5% differed by more than a factor of 2 between the systems; these included some doses to walls of the GI tract, a significant result in relation to their high tissue weighting factors. Some of the largest differences in dose were associated with organs of lower significance in terms of radiosensitivity (e.g. thymus). In this small series, voxel organ doses tended to exceed MIRD values, on average, and a 10% difference was significant when all 238 organ doses were considered as a single group. In 12 comparisons of effective dose, the mean voxel to MIRD ratio was 1.07 (range 0.72–1.32). It was shown for the majority of cases that, whereas some large differences in SAF values exist, differences in source organ and effective dose values between the MIRD and voxel methods were largely accounted for by the respective organ mass differences. The reasons for various organ dose differences with the selected radiopharmaceuticals are discussed. Taking biological variation into account, there is reasonable agreement between the two methods but some significant differences exist that warrant further investigation. More extensive comparisons involving a wide variety of voxel phantoms are required to establish whether realistic voxel phantoms should eventually replace the MIRD system.
AU  - Smith, T.*
AU  - Petoussi-Henß, N.
AU  - Zankl, M.
C1  - 21653
C2  - 19808
SP  - 1387-1398
TI  - Comparison of internal radiation doses estimated by MIRD and voxel techniques for a "family" of phantoms.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 27
IS  - 9
PY  - 2000
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Dextran (clinical grade, average mol. wt. 82,200) was labelled with 99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free 99mTcO4 -was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200-600 μCi/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample, was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed, and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12%±0.77% to 4.28%±1.57% at 3 and 2 h, respectively (P<0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that 99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.
AU  - Ercan, M.T.
AU  - Schneidereit, M.
AU  - Senekowitsch, R.
AU  - Kriegel, H.
C1  - 41716
C2  - 38197
SP  - 80-84
TI  - Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 11
IS  - 2-3
PY  - 1985
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - The uptake of the bone-seeking radiopharmaceutical 99(m)Tc-MDP in defects of the mandibula was quantitated from scintigraphic images. Activity ratios were calculated by means of ROI-technique. The four selected regions contained two control regions and two with mandibula defects. One defect was filled with a fibrin bonding agent and one remained unfilled. The time course of the ratios showed a significantly higher uptake of 99(m)Tc-MDP in the region of the filled defect in comparison with the unfilled defect. The measurement of the residual defect areas from histological sections prepared 18 weeks after introduction of the defects confirmed the much more intensive ossification in the filled defects which could also be derived from the evaluation of the scintigrams. The results indicate that it is possible to follow up osseous repair by quantitative evaluation of scintigraphic images.
AU  - Senekowitsch, R.
AU  - Kriegel, H.
AU  - Siegle, M.
AU  - Brachmann, F.
C1  - 41900
C2  - 38579
SP  - 155-157
TI  - Evaluation of ossification in jaw defects by radio-nuclide imaging.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 7
IS  - 4
PY  - 1982
SN  - 1619-7070
ER  - 

TY  - JOUR
AU  - Roth, P.
AU  - Werner, E.E.
AU  - Kaltwasser, J.P.
C1  - 41856
C2  - 40433
SP  - No.144
TI  - Ferrokinetics: Ineffective erythropoiesis and iron accumulation in bone marrow reticuloendothelial cells.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 6
IS  - 5
PY  - 1981
SN  - 1619-7070
ER  - 

TY  - JOUR
AB  - Our preliminary experimental and clinical results with 201Tl myocardial scanning are presented. 48 patients with normal coronary vessels, acute transmural myocardial infarction, localized and diffuse coronary heart diseases and congestive myocardiopathy were investigated. Results of scans and the usual cardiological investigations were in good agreement thus justifying further use of 201Tl myocardial scintigraphy as an adjunctive method in cardiology.
AU  - Pabst, H.W.*
AU  - Hör, G.*
AU  - Lichte, H.*
AU  - Sebening, H.*
AU  - Kriegel, H.
C1  - 33205
C2  - 35622
SP  - 19-25
TI  - Experience with 201Thallium in detection of myocardial infarction.
JO  - Eur. J. Nucl. Med. Mol. Imaging
VL  - 1
IS  - 1
PY  - 1976
SN  - 1619-7070
ER  -