TY  - JOUR
AB  - α-therapy with 225Ac-labeled radioligands targeting prostate-specific membrane antigen (PSMA) has emerged as a promising treatment option for advanced metastatic castration-resistant prostate cancer. Because of α-recoil, the progeny is released from the PSMA-targeted molecule and can undergo redistribution, contributing to off-target toxicity. Here, we report on biodistribution and dosimetry studies of [225Ac]Ac-PSMA I&T performed in mice to investigate the pharmacokinetics of the radioligand compared with unbound progeny. Moreover, the cellular uptake and externalization kinetics of [225Ac]Ac-PSMA I&T were compared with those of its 177Lu-labeled analog. Methods: In vitro studies were performed on LNCaP and PC3 PIP cells. Biodistribution studies (performed 10 min to 7 d after injection) were conducted in LNCaP tumor-bearing and healthy mice. Equilibrium uptake was determined 24 h after dissection by quantification of 221Fr (218 keV) and 213Bi (440 keV). Tissues of interest (kidneys, salivary glands, and tumor tissue) were measured immediately after dissection until reaching equilibrium to determine the time-dependent activity distribution of 221Fr and 213Bi. Absorbed doses were calculated using MIRDcalc, assuming decay of the progeny at the site of the first decay versus taking into account redistribution of unbound progeny. Results: [225Ac]Ac-PSMA I&T demonstrated cell-binding characteristics and cellular retention similar to those of [177Lu]Lu-PSMA I&T. In biodistribution studies, no redistribution of 221Fr and 213Bi was measured from tumor tissue. Higher uptake of 213Bi was found in the kidneys (2-fold higher at 10 min and at 1 h after injection) and salivary glands (1.7-fold and 8.5-fold higher at 10 min and 1 h after injection, respectively) at the time of death compared with equilibrium. This contribution increased the absorbed dose in the kidneys and salivary glands by a factor of 1.3 and 2.5, respectively, assuming uptake of 221Fr and in situ formation of 213Bi. Conclusion: The PSMA-targeting characteristics and pharmacokinetics of [225Ac]Ac-PSMA I&T are similar to those of [177Lu]Lu-PSMA I&T. The progeny of [225Ac]Ac-PSMA I&T is trapped in tumor tissue. Uptake of liberated decay products into the salivary glands and kidneys was identified as an additional factor explaining the increased side effects of 225Ac therapy compared with 177Lu-based radioligands.
AU  - Wurzer, A.*
AU  - Sun, B.*
AU  - Saleh, S.
AU  - Brosch-Lenz, J.*
AU  - Fischer, S.*
AU  - Kossatz, S.*
AU  - Hürkamp, K.
AU  - Li, W.B.
AU  - Eiber, M.*
AU  - Morgenstern, A.*
AU  - Bruchertseifer, F.*
AU  - Weber, W.*
AU  - D'Alessandria, C.*
C1  - 75709
C2  - 58217
TI  - [225Ac]Ac-PSMA I&T: A preclinical investigation on the fate of decay nuclides and their influence on dosimetry of salivary glands and kidneys.
JO  - J. Nucl. Med.
PY  - 2025
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.
AU  - Moser, R.*
AU  - Pfeiffer, S.*
AU  - Cala, L.*
AU  - Klein, E.*
AU  - Kiechle, M.*
AU  - Behzadi, S.T.*
AU  - Fallenberg, E.M.*
AU  - Combs, S.E.
AU  - Weber, W.*
AU  - Borm, K.J.*
C1  - 70535
C2  - 55650
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 845-850
TI  - Detecting metastatic patterns of oligometastatic breast cancer: A comparative analysis of 18F-FDG PET/CT and conventional CT imaging.
JO  - J. Nucl. Med.
VL  - 65
IS  - 6
PB  - Soc Nuclear Medicine Inc
PY  - 2024
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Esophageal adenocarcinoma causes 6% of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study, we aimed to investigate the feasibility of an epidermal growth factor receptor (EGFR)–targeted tracer, cetuximab-800CW, to improve detection of early-stage esophageal adenocarcinoma. Methods: We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow-band imaging, and NIR-FME in 15 patients with Barrett esophagus (BE). Intrinsic fluorescence values were quantified using multidiameter single-fiber reflectance and single-fiber fluorescence spectroscopy. Back-table imaging, histopathologic examination, and EGFR immunohistochemistry on biopsy samples collected during NIR-FME procedures were performed and compared with in vivo imaging results. Results: Immunohistochemical preanalysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE–visible lesions and 5 HD-WLE–invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared with nondysplastic BE as shown by multidiameter single-fiber reflectance/single-fiber fluorescence, reflecting a target-to-background ratio of 1.5. Invisible dysplastic lesions also showed increased fluorescence, with a target-to-background ratio of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. Conclusion: This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and narrow-band imaging.
AU  - Gabriels, R.Y.*
AU  - van Heijst, L.E.*
AU  - Hooghiemstra, W.T.R.*
AU  - van der Waaij, A.M.*
AU  - Kats-Ugurlu, G.*
AU  - Karrenbeld, A.*
AU  - Robinson, D.J.*
AU  - Tenditnaya, A.
AU  - Ntziachristos, V.
AU  - Gorpas, D.
AU  - Nagengast, W.B.*
C1  - 68576
C2  - 53711
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 803-808
TI  - Detection of early esophageal neoplastic barrett lesions with quantified fluorescence molecular endoscopy using Cetuximab-800CW.
JO  - J. Nucl. Med.
VL  - 64
IS  - 5
PB  - Soc Nuclear Medicine Inc
PY  - 2023
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Amino acid PET is an established method to assist differential diagnosis of therapy-related changes versus recurrence in gliomas. However, its diagnostic value in brain metastases is yet to be determined. The goal of this study was to summarize evidence on the diagnostic utility of amino acid PET in recurrent brain metastases. Methods: The medical databases MEDLINE, EMBASE, and the Cochrane Library were screened for English-language studies with at least 10 patients who had undergone first-line treatment including radiotherapy and in whom a final diagnosis had been determined by histologic examination or imaging and clinical follow-up. Pooled estimates with 95% CIs were calculated. Heterogeneity was assessed using I2 statistics. Results: Following the above criteria, 12 studies with the tracers methyl-[11C]-methionine (n 5 6), O-(2-[18F]fluoroethyl)-L-tyrosine (n 5 3), methyl-[11C]-methionine and O-(2-[18F]fluoroethyl)-L-tyrosine (n 5 1), and 6-[18F]fluoro-L-dopa (n 5 2), with a total of 547 lesions in 397 patients, were included. Pooled sensitivity and specificity were 82% (95% CI, 76–86) and 84% (95% CI, 79–88), respectively. Pooled positive and negative predictive values were 84% (95% CI, 77–90) and 83% (95% CI, 77–88), respectively. Positive and negative likelihood ratios, and diagnostic odds ratio were 3.8 (95% CI 3.0–4.8), 0.3 (95% CI 0.2–0.3), and 16.7 (95% CI 10.8–25.9), respectively. Heterogeneity was overall low. Conclusion: The present meta-analysis indicates a good accuracy of amino acid PET in the differential diagnosis of recurrent brain metastases. In particular, specificity of 84% suggests that amino acid PET may reduce the number of invasive procedures and overtreatment in patients with treatment-related changes. This study provides class IIa evidence on the utility of amino acid PET in the differential diagnosis of recurrent brain metastases.
AU  - Schlürmann, T.*
AU  - Waschulzik, B.*
AU  - Combs, S.E.
AU  - Gempt, J.*
AU  - Wiestler, B.*
AU  - Weber, W.*
AU  - Yakushev, I.*
C1  - 68564
C2  - 53706
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 816-821
TI  - Utility of amino acid PET in the differential diagnosis of recurrent brain metastases and treatment-related changes: A meta-analysis.
JO  - J. Nucl. Med.
VL  - 64
IS  - 5
PB  - Soc Nuclear Medicine Inc
PY  - 2023
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Fluorescence imaging is an emerging imaging technique that has shown many benefits for clinical care. Currently, the field is in rapid clinical translation, and an unprecedented number of clinical trials are performed. Clinicians are inundated with numerous opportunities and combinations of different imaging modalities. To streamline this process, a multidisciplinary approach is needed with drug discovery, software and systems engineering, and translational medicine. Here, we discuss the main constituents of a uniform fluorescence imaging protocol to match the clinical need and ensure consistent study designs and reliable data collection in clinical trials. In an era in which the potential of fluorescence imaging has become evident, consistent conduct of studies, data analysis, and data interpretation is essential for implementation into the standard of care.
AU  - Heeman, W.*
AU  - Vonk, J.*
AU  - Ntziachristos, V.
AU  - Pogue, B.W.*
AU  - Dierckx, R.A.J.O.*
AU  - Kruijff, S.*
AU  - van Dam, G.M.*
C1  - 64973
C2  - 51990
SP  - 640-645
TI  - A guideline for clinicians performing clinical studies with fluorescence imaging.
JO  - J. Nucl. Med.
VL  - 63
IS  - 5
PY  - 2022
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of prostate cancer theranostic agents. F-18-rhPSMA-7 offers the advantages of F-18 labeling and low urinary excretion compared with 68Ga-PSMA-11. Here, we compare the frequency of non-tumor-related uptake and tumor positivity with Ga-68-PSMA-11 and F-18-rhPSMA-7 in patients with primary or recurrent prostate cancer. Methods: This retrospective matched-pair comparison matched 160 F-18-rhPSMA-7 with 160 Ga-68-PSMA-11 PET/CT studies for primary staging (n = 33) and biochemical recurrence (n = 127) according to clinical characteristics. Two nuclear medicine physicians reviewed all scans, first identifying all PET-positive lesions and then differentiating lesions suggestive of prostate cancer from those that were benign, on the basis of known pitfalls and ancillary information from CT. For each region, the SUVmax of the lesion with the highest PSMA ligand uptake was noted. Tumor positivity rates were determined, and SUVmax was compared separately for each tracer. Results: F-18-rhPSMA-7 and Ga-68-PSMA-11 PET revealed 566 and 289 PSMA ligand-positive lesions, respectively. Of these, 379 and 100 lesions, equaling 67.0% and 34.6%, respectively, of all PSMA-positive lesions, were considered benign. The distribution of their etiology was similar (42%, 24%, and 25% with 18F-rhPSMA-7 vs. 32%, 24%, and 38% with Ga-68-PSMA-1 1 for ganglia, bone, and unspecific lymph nodes, respectively). All primary tumors were positive with both agents (n = 33 each), whereas slightly more metastatic lesions were observed with Ga-68-PSMA-11 in both disease stages (113 for F-18-rhPSMA-7 and 124 for Ga-68-PSMA-11). The SUVmax of F-18-rhPSMA-7 and Ga-68-PSMA-1 1 did not differ (P > 0.05) in local recurrence or primary prostate cancer; however, the tumor-to-bladder ratio was significantly higher with 18F-rhPSMA-7 (4.9 +/- 5.3 vs. 2.2 +/- 3.7, P = 0.02, for local recurrence; 9.8 +/- 9.7 vs. 2.3 +/- 2.6, P < 0.001, for primary prostate cancer). Conclusion: The tumor positivity rate was consistently high for Ga-68-PSMA-1 1 and F-18-rhPSMA-7. Both tracers revealed a considerable number of areas of uptake that were reliably identified as benign by trained physicians making use of corresponding morphologic imaging and known PSMA pitfalls. These were more frequent with F-18-rhPSMA-7. However, the matched-pair comparison could have introduced a source of bias. Adequate reader training can allow physicians to differentiate benign uptake from disease and be able to benefit from the logistical and clinical advantages of F-18-rhPSMA-7.
AU  - Kroenke, M.*
AU  - Mirzoyan, L.*
AU  - Horn, T.*
AU  - Peeken, J.C.
AU  - Wurzer, A.*
AU  - Wester, H.*
AU  - Makowski, M.*
AU  - Weber, W.A.*
AU  - Eiber, M.*
AU  - Rauscher, I.*
C1  - 63544
C2  - 51440
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 1082-1088
TI  - Matched-pair comparison of Ga68-PSMA-11 and F18-rhPSMA-7 PET/CT in patients with primary and biochemical recurrence of prostate cancer: Frequency of non-tumor-related uptake and tumor positivity.
JO  - J. Nucl. Med.
VL  - 62
IS  - 8
PB  - Soc Nuclear Medicine Inc
PY  - 2021
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - This study aimed at evaluating hybrid multispectral optoacoustic tomography/ultrasound for imaging of thyroid disorders, including Graves' disease and thyroid nodules. Methods: The functional biomarkers and tissue parameters deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin, saturation of hemoglobin, fat content, and water content were analyzed in thyroid lobes affected by Graves' disease (n = 6), thyroid lobes with healthy tissue (n = 8), benign thyroid nodules (n = 13), and malignant thyroid nodules (n = 3). Results: In Graves' disease, significantly higher deoxygenated hemoglobin (3.18 +/- 0.52 vs. 2.13 +/- 0.62; P = 0.0055) and total hemoglobin (8.34 +/- 0.88 vs. 6.59 +/- 1.16; P = 0.0084) and significantly lower fat content (0.64 +/- 0.37 vs. 1.69 +/- 1.25; P = 0.0293) were found than in healthy controls. Malignant thyroid nodules showed significantly lower saturation of hemoglobin (55.4% +/- 2.6% vs. 60.8% +/- 7.2%; P = 0.0393) and lower fat content (0.62 +/- 0.19 vs. 1.46 +/- 0.87; P = 0.1295) than benign nodules. Conclusion: This pilot study showed the applicability and the potential of hybrid multispectral optoacoustic tomography/ultrasound to semiquantitatively provide tissue characterization and functional parameters in thyroid disorders for improved noninvasive diagnostics of thyroid diseases.
AU  - Roll, W.*
AU  - Markwardt, N.A.
AU  - Masthoff, M.*
AU  - Helfen, A.*
AU  - Claussen, J.*
AU  - Eisenblätter, M.*
AU  - Hasenbach, A.*
AU  - Hermann, S.*
AU  - Karlas, A.
AU  - Wildgruber, M.*
AU  - Ntziachristos, V.
AU  - Schäfers, M.*
C1  - 55649
C2  - 46509
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 1461-1466
TI  - Multispectral optoacoustic tomography of benign and malignant thyroid disorders: A pilot study.
JO  - J. Nucl. Med.
VL  - 60
IS  - 10
PB  - Soc Nuclear Medicine Inc
PY  - 2019
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson disease (PD) and other Lewy body disorders. Spatial covariance analysis of F-18-FDG PET data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it with the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we studied the expression of the iRBD pattern in de novo PD patients.Methods: The iRBD-related pattern was identified in F-18-FDG PET scans of 21 patients with polysomnographically confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in F-18-FDG PET scans of 44 controls and 38 de novo, treatment-naive PD patients. Of these 38 PD patients, 24 had probable REM sleep behavior disorder (RBD) according to the Mayo Sleep Questionnaire. Neuropsychologic evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom 16 also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms.Results: The iRBD-related pattern was characterized by relative hypermetabolism in the cerebellum, brain stem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in the middle cingulate, temporal, occipital, and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBD-related pattern was significantly expressed in PD patients compared with controls (P < 0.0001). iRBD-related pattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern (iRBDRP) expression was higher in PD-MCI patients than in PD patients with preserved cognition (P 5 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP (r = 0.94, P < 0.0001).Conclusion: Our results show that the iRBDRP is an early manifestation of the PDRP. Expression of both PDRP and iRBDRP was higher in patients with a more severe form of PD (PD-MCI), which indicates that expression of the 2 patterns increases with disease severity.
AU  - Meles, S.K.*
AU  - Renken, R.J.*
AU  - Janzen, A.*
AU  - Vadasz, D.*
AU  - Pagani, M.*
AU  - Arnaldi, D.*
AU  - Morbelli, S.*
AU  - Nobili, F.*
AU  - Mayer, G.*
AU  - Leenders, K.L.*
AU  - Oertel, W.H.
C1  - 54356
C2  - 45482
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 1437-1444
TI  - The metabolic pattern of idiopathic REM sleep behavior disorder reflects early-stage Parkinson’s disease.
JO  - J. Nucl. Med.
VL  - 59
IS  - 9
PB  - Soc Nuclear Medicine Inc
PY  - 2018
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - The prostate-specific membrane antigen (PSMA)-targeted radiotracers Ga-68/Lu-177-PSMA-I&T and Tc-99m-PSMA-I&S (for imaging and surgery) are currently successfully used for clinical PET imaging, radionuclide therapy, and radioguided surgery of metastatic prostate cancer. To additionally exploit the high sensitivity and spatial resolution of fluorescence imaging for improved surgical guidance, a PSMA-I&T-based hybrid tracer, PSMA-I&F (DOTAGA-k(Sulfo-Cy5)-y-nal-k-Sub-KuE), has been developed and evaluated. Methods: The in vitro PSMA-targeting efficiency of PSMA-I&F, the reference PSMA-I&T, and their corresponding Ga-nat-/Ga-68- and Lu-nat/Lu-177 counterparts was determined in LNCaP cells via competitive binding assays (IC50) and dual-tracer radioligand and fluorescence internalization studies. Biodistribution and small-animal PET imaging studies were performed in CB17 SCID and LNCaP xenograft-bearing SHO mice, respectively, and complemented by intraoperative far-red fluorescence imaging using a clinical laparoscope. Additionally, fully automated serial cryosectioning and fluorescence imaging of 1 tumor-bearing animal as well as PSMA immunohistochemistry and fluorescence microscopy of organ cryosections (tumor, kidney, spleen) were also performed. Results: Compared with the parent PSMA-I&T analogs, the PSMA affinities of PSMA-I&F and its Ga-nat-/Lu-nat-complexes remained high and unaffected by dye conjugation (7.9 < IC50 < 10.5 nM for all ligands). The same was observed for the internalization of Ga-68- and Lu-177-PSMA-I&F. In vivo, blood clearance of Ga-68- and Lu-177-PSMA-I&F was only slightly delayed by high plasma protein binding (94%-95%), and very low accumulation in nontarget organs was observed already at 1 h after injection. Dynamic PET imaging confirmed PSMA-specific (as demonstrated by coinjection of 2-PMPA) uptake into the LNCaP xenograft (4.5% +/- 1.8 percentage injected dose per gram) and the kidneys (106% +/- 23 percentage injected dose per gram). Tumor-to-background ratios of 2.1, 5.2, 9.6, and 9.6 for blood, liver, intestines, and muscle, respectively, at 1 h after injection led to excellent imaging contrast in Ga-68-PSMA-I&F PET and in intraoperative fluorescence imaging. Furthermore, fluorescence imaging of tissue cryosections allowed high-resolution visualization of intraorgan PSMA-I&F distribution in vivo and its correlation with PSMA expression as determined by immunohistochemistry. Conclusion: Thus, with its high PSMA-targeting efficiency and favorable pharmacokinetic profile, Ga-68/Lu-177-PSMA-I&F serves as an excellent proof-of-concept compound for the general feasibility of PSMA-I&T-based hybrid imaging. The PSMA-I&T scaffold represents a versatile PSMA-targeted lead structure, allowing relatively straightforward adaptation to the different structural requirements of dedicated nuclear or hybrid imaging agents.
AU  - Schottelius, M.*
AU  - Wurzer, A.*
AU  - Wissmiller, K.*
AU  - Beck, R.*
AU  - Koch, M.
AU  - Gorpas, D.
AU  - Notni, J.*
AU  - Buckle, T.*
AU  - van Oosterom, M.N.*
AU  - Steiger, K.*
AU  - Ntziachristos, V.
AU  - Schwaiger, M.*
AU  - van Leeuwen, F.W.B.*
AU  - Wester, H.J.*
C1  - 54603
C2  - 45687
CY  - 1850 Samuel Morse Dr, Reston, Va 20190-5316 Usa
SP  - 71-78
TI  - Synthesis and preclinical characterization of the PSMA-targeted hybrid tracer PSMA-I&F for nuclear and fluorescence imaging of prostate cancer.
JO  - J. Nucl. Med.
VL  - 60
IS  - 1
PB  - Soc Nuclear Medicine Inc
PY  - 2018
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - F-18-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT F-18-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective beta 3 adrenergic receptor agonist CL 316, 243 and under-went metabolic cage, infrared thermal imaging and F-18-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy-H-3-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT F-18-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-H-3-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT F-18-FDG uptake independently of UCP1 thermogenic function.
AU  - Hankir, M.K.*
AU  - Kranz, M.*
AU  - Keipert, S.
AU  - Weiner, J.*
AU  - Andreasen, S.G.*
AU  - Kern, M.J.*
AU  - Patt, M.*
AU  - Kloeting, N.*
AU  - Heiker, J.T.*
AU  - Brust, P.*
AU  - Hesse, S.*
AU  - Jastroch, M.
AU  - Fenske, W.K.*
C1  - 51553
C2  - 43252
CY  - Reston
SP  - 1100-1103
TI  - Dissociation between brown adipose tissue 18F-FDG uptake and thermogenesis in uncoupling protein 1 deficient mice.
JO  - J. Nucl. Med.
VL  - 58
IS  - 7
PB  - Soc Nuclear Medicine Inc
PY  - 2017
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Antibodies have become an established treatment modality in cancer therapy during the last decade. However, these treatments often suffer from insufficient and heterogeneous response despite validated antigen or target receptor expression in the tumor. In fact, therapeutic success depends both on the presence and accessibility of the tumor antigen by the antibody. In search of a suitable preclinical animal model to evaluate the mechanisms of tumor heterogeneity and hemodynamics, we characterized two exemplary non-Hodgkin lymphoma subtypes with comparable CD20 expression and metabolism, SUDHL-4 and Granta, using multimodal imaging techniques. METHODS: To investigate in vivo biodistribution, two differently modified αCD20 antigen-binding fragments (Fab), prepared (i) by PASylation and (ii) by fusion with an albumin-binding domain (ABD), were radiolabeled with (125)I and intravenously injected into immunocompromised mice bearing corresponding xenografts. RESULTS: Validation with (18)F-FDG revealed similar distribution of vital tumor tissue 1 h p.i. However, large differences in tumor uptake were observed when applying the CD20-specific radiotracers (125)I-Fab-ABD and (125)I-Fab-PAS200 with 12.3 and 2.4 % ID/g, respectively, for Granta in comparison with 3.5 and 0.75 % ID/g, respectively, for SUDHL-4 xenografts 24 h p.i. 3D light-sheet fluorescence microscopy with Cy5-Fab-PAS200 confirmed better tracer extravasation in the Granta tumors. Moreover, dynamic contrast enhanced MRI imaging revealed significantly reduced tumor perfusion in the SUHDL-4 xenografts. CONCLUSION: Tracer uptake was highly dependent on local tumor perfusion as well as Fab permeation in the SUDHL-4 and Granta tumors. Thus, the SUDHL-4 xenograft offers an excellent model system to investigate the influence of therapies affecting tumor angiogenesis.
AU  - Mendler, C.T.*
AU  - Feuchtinger, A.
AU  - Heid, I.*
AU  - Aichler, M.
AU  - D'Alessandria, C.*
AU  - Pirsig, S.*
AU  - Blechert, B.*
AU  - Wester, H.J.*
AU  - Braren, R.*
AU  - Walch, A.K.
AU  - Skerra, A.*
AU  - Schwaiger, M.*
C1  - 49095
C2  - 41641
CY  - Reston
SP  - 1971-1977
TI  - Tumor uptake of anti-CD20 Fabs depends on tumor perfusion.
JO  - J. Nucl. Med.
VL  - 57
IS  - 12
PB  - Soc Nuclear Medicine Inc
PY  - 2016
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Dose coefficients of radiopharmaceuticals have been published by the International Commission on Radiological Protection (ICRP) and the Medical Internal Radiation Dose (MIRD) Committee, but without information concerning uncertainties. The uncertainty information of dose coefficients is important, for example, to compare alternative diagnostic methods and choose the method that causes the lowest patient exposure with appropriate and comparable diagnostic quality. For the study presented here, an uncertainty analysis method was developed and used to calculate the uncertainty of the internal doses of seven common radiopharmaceuticals. METHODS: On the basis of the generalized schema of dose calculation recommended by ICRP and the MIRD Committee, an analysis based on propagation of uncertainty was developed and applied for seven radiopharmaceuticals. The method takes into account the uncertainties contributed from pharmacokinetic models and the so-called S values derived from several voxel computational phantoms previously developed at Helmholtz Zentrum München. Random and Latin hypercube sampling techniques were used to sample parameters of pharmacokinetic models and S values, and the uncertainties of absorbed doses and effective doses were calculated. RESULTS: The uncertainty factors (square root of ratio between 97.5th and 2.5th percentiles) for organ absorbed doses are in the range of 1.1 to 3.3. Uncertainty values of effective doses are lower in comparison to absorbed doses, the maximum value being approximately 1.4. The ICRP reference values showed a deviation comparable to the effective dose calculated in this study. CONCLUSION: A general statistical method was developed for calculating the uncertainty of absorbed doses and effective doses for seven radiopharmaceuticals. The dose uncertainties can be used to further identify the most important parameters in the dose calculation and provide reliable dose coefficients for risk analysis of the patients in nuclear medicine.
AU  - Spielmann, V.
AU  - Li, W.B.
AU  - Zankl, M.
AU  - Oeh, U.
AU  - Hoeschen, C.
C1  - 47301
C2  - 37852
SP  - 122-128
TI  - Uncertainty quantification in internal dose calculations for seven selected radiopharmaceuticals.
JO  - J. Nucl. Med.
VL  - 57
IS  - 1
PY  - 2016
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular-guided endoscopy with targeted near-infrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR) targeted fluorescent tracers during ex vivo colonoscopy with a NIR endoscopy platform. METHODS: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples: 48 sessile serrated adenomas/polyps (SSA/P), 70 sporadic high-grade dysplastic (HGD) adenomas, 19 hyperplastic polyps (HP) and tissue derived from patients with Lynch syndrome (LS): 78 low-grade dysplastic (LGD) adenomas, 57 HGD adenomas and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116luc tumors received intravenously bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW or sodium chloride. Three days later, 8 resected HCT116luc tumors (2-5 mm) were stitched into one freshly resected human colon specimen and followed by an ex vivo molecular-guided colonoscopy procedure. RESULTS: Immunohistochemistry showed high VEGF-A expression in 79-96% and high EGFR expression in 51-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions compared to the adjacent normal colon crypts. During ex vivo molecular-guided endoscopy all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing respectively stromal and cell membrane fluorescence. CONCLUSION: VEGF-A is a promising target for molecular-guided fluorescence endoscopy as it showed a high protein expression, especially in SSA/P and LS. We demonstrate the feasibility to visualize small tumors real-time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field 'red-flag' technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.
AU  - Tjalma, J.J.*
AU  - Garcia-Allende, P.
AU  - Hartmans, E.*
AU  - Terwisscha van Scheltinga, A.G.*
AU  - Boersma-van Ek, W.*
AU  - Glatz, J.
AU  - Koch, M.
AU  - van Herwaarden, Y.J.*
AU  - Bisseling, T.M.*
AU  - Nagtegaal, I.D.*
AU  - Timmer-Bosscha, H.*
AU  - Koornstra, J.J.*
AU  - Karrenbeld, A.*
AU  - Kleibeuker, J.H.*
AU  - van Dam, G.M.*
AU  - Ntziachristos, V.
AU  - Nagengast, W.B.*
C1  - 47563
C2  - 40674
CY  - Reston
SP  - 480-485
TI  - Molecular-guided endoscopy targeting vascular endothelial growth factor A for improved colorectal polyp detection.
JO  - J. Nucl. Med.
VL  - 57
IS  - 3
PB  - Soc Nuclear Medicine Inc
PY  - 2016
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - We investigated in vitro and in vivo the optoacoustic responses of a silicon naphthalocyanine (SiNc), considered herein as a reporter molecule for optoacoustic imaging, elucidating its efficiency for optoacoustic (photoacoustic) signal generation and examined the in vivo performance achieved. METHODS: SiNc solutions were prepared using Cremophor E.L. in water and evaluated for light absorbing and photoacoustic contrast generating properties. Photostability and singlet oxygen generation were investigated under pulsed laser illumination and validated using photoabsorbance. HT-29 mice tumor models were used to assess the biodistribution of the compound and its performance as an optoacoustic contrast agent in vivo. RESULTS: SiNc was found to generate superior optoacoustic signals compared to the commonly used Indocyanine Green (ICG). Multispectral optoacoustic tomography (MSOT) of mouse tumors efficiently resolved the biodistribution of SiNc and the underlying perfusion parameters in vivo. In addition, we demonstrate how light-triggered SiNc reactions with molecular oxygen can be potentially sensed and discuss the relation of these measurements to the biochemical process involved in photothermal treatment. CONCLUSION: SiNc appears to be a promising family of contrast agent for optoacoustic imaging. Further development possibilities promise to expand its use in purely contrast generation settings, as well as its photodynamic therapy application.
AU  - Bézière, N.
AU  - Ntziachristos, V.
C1  - 43125
C2  - 36007
CY  - Reston
SP  - 323-328
TI  - Optoacoustic imaging of naphthalocyanine: Potential for contrast enhancement and therapy monitoring.
JO  - J. Nucl. Med.
VL  - 56
IS  - 2
PB  - Soc Nuclear Medicine Inc
PY  - 2015
SN  - 0161-5505
ER  - 

TY  - JOUR
AU  - Notni, J.*
AU  - Hofman, F.*
AU  - Steiger, K.
AU  - Reich, D.*
AU  - Kapp, T.G.*
AU  - Rechenmacher, F.*
AU  - Kessler, H.*
AU  - Wester, H.J.*
C1  - 44895
C2  - 37158
CY  - Reston
TI  - Ga-68-Aquibeprin and Ga-68-Avebetrin for complementary, selective PET imaging of integrin subtypes alpha(5)beta(1) and alpha(v)beta(3).
JO  - J. Nucl. Med.
VL  - 56
PB  - Soc Nuclear Medicine Inc
PY  - 2015
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). MIBG targets cell membrane and vesicular catecholamine transporters of chromaffin cells and facilitates localization of the primary tumor and metastatic lesions. Its specificity for the diagnosis of adrenomedullary chromaffin cell tumors can be jeopardized by physiological uptake by the normal adrenal medulla. The aim of this study was to distinguish between PPGLs and normal adrenal glands by evaluating semi-quantitative (123)I-MIBG uptake and to examine genotype-specific differences in correlation with expression of catecholamine transporter systems. METHODS: Sixty-two PPGLs collected from 57 patients with hereditary mutations in SDHA (n = 1), SDHB (n = 2), SDHD (n = 4), VHL (n = 2), RET (n = 12), NF1 (n = 2), MAX (n = 1) and with sporadic PPGLs (n = 33) were investigated. Pre-operative planar and single-photon emission computed tomographic (SPECT) images were semi-quantitatively analyzed using uptake measurements. Tumor-to-liver (T/L) and normal-adrenal-to-liver (NA/L) ratios were calculated and correlated with clinical characteristics including genotype, tumor size and plasma metanephrines concentrations. The expression of norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT-1) was evaluated immunohistochemically in paraffin-embedded tumor tissues. RESULTS: Mean T/L ratios of PPGL lesions were significantly higher than NA/L ratios (p<0.001). Cut-off values to distinguish between physiological and pathological adrenal uptake were established at 0.7 (100% sensitivity, 10.3% specificity) and 4.3 (100% specificity, 66.1% sensitivity). No statistically significant differences in (123)I-MIBG uptake were found across PPGLs of different genotypes. Mean NET expression in hereditary cluster 2 (RET, NF1, MAX) and apparently sporadic tumors was significantly higher than for hereditary cluster 1 (SDHx, VHL) PPGLs (P = 0.011 and P = 0.006, respectively). Mean VMAT-1 expression in hereditary cluster 1 PPGLs was significantly higher than for cluster 2 tumors (P = 0.010). (123)I-MIBG uptake significantly correlated with maximum tumor diameter (P = 0.002). MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. CONCLUSION: Liver normalized semi-quantitative (123)I-MIBG uptake may be helpful to distinguish between pheochromocytoma and physiological adrenal uptake. Genotype-specific differences in expression of NET and VMAT-1 do not translate into differences in (123)I-MIBG uptake.
AU  - van Berkel, A.*
AU  - Upendrao, J.*
AU  - Lenders, J.*
AU  - Pellegata, N.S.
AU  - Kusters, B.*
AU  - Piscaer, I.*
AU  - Hermus, A.R.*
AU  - Plantinga, T.S.*
AU  - Langenhuijsen, H.*
AU  - Vriens, D.*
AU  - Janssen, M.*
AU  - Gotthardt, M.*
AU  - Timmers, H.*
C1  - 44430
C2  - 36840
CY  - Reston
SP  - 839-846
TI  - Semi-quantitative 123I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiological adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters.
JO  - J. Nucl. Med.
VL  - 56
IS  - 6
PB  - Soc Nuclear Medicine Inc
PY  - 2015
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - UNLABELLED: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of αvβ3 integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models. METHODS: Immunohistochemistry and Western blot were used for characterization of αvβ3 expression in murine and human PDAC. We applied IntegriSense 680 fluorescence molecular tomography, intraoperative fluorescence imaging, and (68)Ga-NODAGA-RGD PET for αvβ3 integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a(+/Cre);Kras(+/LSL-G12D);p53(LoxP/LoxP) mice. (NODAGA is 1,4,7-triazacyclononane-1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine-glycine-aspartic acid.) RESULTS: αvβ3 integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and (68)Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders. CONCLUSION: Imaging approaches targeting αvβ3 integrin expand the potential of molecular imaging for identification of αvβ3-positive PDAC with potential implications in early detection, fluorescence-guided surgery, and therapy monitoring.
AU  - Trajkovic-Arsic, M.*
AU  - Mohajerani, P.
AU  - Sarantopoulos, A.
AU  - Kalideris, E.*
AU  - Steiger, K.*
AU  - Esposito, I.*
AU  - Ma, X.
AU  - Themelis, G.
AU  - Burton, N.C.
AU  - Michalski, C.W.*
AU  - Kleeff, J.*
AU  - Stangl, S.*
AU  - Beer, A.J.*
AU  - Pohle, K.*
AU  - Wester, H.J.*
AU  - Schmid, R.M.*
AU  - Braren, R.*
AU  - Ntziachristos, V.
AU  - Siveke, J.T.*
C1  - 30762
C2  - 33840
CY  - Reston
SP  - 446-451
TI  - Multimodal molecular imaging of integrin αvβ3 for in vivo detection of pancreatic cancer.
JO  - J. Nucl. Med.
VL  - 55
IS  - 3
PB  - Soc Nuclear Medicine Inc
PY  - 2014
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - [object Object]: We evaluated (18)F-LMI1195 (1-(3-bromo-4-(3-(18)F-fluoro-propoxy)benzyl)guanidine), a metaiodobenzylguanidine (MIBG) analog, for the detection of pheochromocytoma in a preclinical in vivo model of endogenous neuroendocrine tumors (multiple endocrine neoplasia [MENX]). METHODS: Adrenal uptake kinetics of (18)F-LMI1195 were evaluated in healthy Wistar rats (n = 6) by dynamic PET imaging. Distribution of (18)F-LMI1195 was evaluated in tumor-bearing MENX mut/mut rats (n = 10) and control MENX wild-type rats (n = 4) by biodistribution studies and PET imaging. Biodistribution of (18)F-LMI1195 was compared with (123)I-MIBG in MENX mut/mut rats (n = 6) and correlated with histological tumor volume and norepinephrine transporter (NET) expression. Uptake specificity was evaluated by in vivo inhibition of the NET by desipramine (n = 6). Intraadrenal distribution of (18)F-LMI1195 was evaluated by autoradiography. RESULTS: (18)F-LMI1195 showed rapid tracer accumulation in adrenal glands 1 min after tracer injection. Adrenal glands of MENX mut/mut animals showed significantly higher standardized uptake value than MENX wild-type controls (maximum SUV, 10.3 ± 2.3 vs. 6.1 ± 0.9, P < 0.01). Adrenal uptake in MENX mut/mut rats could be inhibited by desipramine, shown by biodistribution studies (0.06 ± 0.01 vs. 0.16 ± 0.05 percentage injected dose, P < 0.01), PET imaging (maximum SUV, 3.8 ± 0.8 vs. 10.3 ± 2.3, P < 0.01), and autoradiography. Adrenal uptake of (18)F-LMI1195 correlated with (123)I-MIBG uptake (r = 0.91), histological tumor volume (r = 0.68), and NET expression (r = 0.50). (18)F-LMI1195 showed an overall favorable distribution for tumor imaging. CONCLUSION: (18)F-LMI1195 shows high and specific accumulation in pheochromocytomas. Its favorable biodistribution makes it a promising PET tracer for tumor imaging. Further studies are warranted to evaluate its clinical value in oncologic indications.
AU  - Gaertner, F.C.*
AU  - Wiedemann, T.
AU  - Yousefi, B.H.*
AU  - Lee, M.S.
AU  - Repokis, I.
AU  - Higuchi, T.*
AU  - Nekolla, S.G.*
AU  - Yu, M.*
AU  - Robinson, S.*
AU  - Schwaiger, M.*
AU  - Pellegata, N.S.
C1  - 27966
C2  - 32881
SP  - 2111-2117
TI  - Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model.
JO  - J. Nucl. Med.
VL  - 54
IS  - 12
PB  - Soc. Nuclear Medicine
PY  - 2013
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Among several techniques considered for surgical and endoscopic imaging, novel optical methods are evolving as a promising approach for interventional guidance. Pilot clinical applications of fluorescence molecular imaging have demonstrated the benefits of using targeted fluorescent agents in cancer surgery. This premise can be extended broadly to interventional guidance through an increasing number of targeted agents and detection techniques. Beyond epi-illumination fluorescence imaging, optoacoustic (photoacoustic) methods are emerging to offer high-resolution cross-sectional optical imaging through several millimeters to centimeters of depth. We present an overview of key recent developments in optical interventional imaging and outline the potential for a paradigm shift in surgical and endoscopic visualization.
AU  - Garcia-Allende, P.
AU  - Glatz, J.
AU  - Koch, M.
AU  - Ntziachristos, V.
C1  - 24807
C2  - 31689
SP  - 664-667
TI  - Enriching the interventional vision of cancer with fluorescent and optoacoustic imaging.
JO  - J. Nucl. Med.
VL  - 54
IS  - 5
PB  - Soc. Nuclear Medicine
PY  - 2013
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - PET with (18)F-choline ((18)F-FCH) is used in the diagnosis of prostate cancer and its recurrences. In this work, biodistribution data from a recent study conducted at Skåne University Hospital Malmö were used for the development of a biokinetic and dosimetric model. METHODS: The biodistribution of (18)F-FCH was followed for 10 patients using PET up to 4 h after administration. Activity concentrations in blood and urine samples were also determined. A compartmental model structure was developed, and values of the model parameters were obtained for each single patient and for a reference patient using a population kinetic approach. Radiation doses to the organs were determined using computational (voxel) phantoms for the determination of the S factors. RESULTS: The model structure consists of a central exchange compartment (blood), 2 compartments each for the liver and kidneys, 1 for spleen, 1 for urinary bladder, and 1 generic compartment accounting for the remaining material. The model can successfully describe the individual patients' data. The parameters showing the greatest interindividual variations are the blood volume (the clearance process is rapid, and early blood data are not available for several patients) and the transfer out from liver (the physical half-life of (18)F is too short to follow this long-term process with the necessary accuracy). The organs receiving the highest doses are the kidneys (reference patient, 0.079 mGy/MBq; individual values, 0.033-0.105 mGy/MBq) and the liver (reference patient, 0.062 mGy/MBq; individual values, 0.036-0.082 mGy/MBq). The dose to the urinary bladder wall of the reference patient varies between 0.017 and 0.030 mGy/MBq, depending on the assumptions on bladder voiding. CONCLUSION: The model gives a satisfactory description of the biodistribution of (18)F-FCH and realistic estimates of the radiation dose received by the patients.
AU  - Giussani, A.
AU  - Janzen, T.
AU  - Uusijärvi-Lizana, H.*
AU  - Tavola, F.*
AU  - Zankl, M.
AU  - Sydoff, M.*
AU  - Bjartell, A.*
AU  - Leide-Svegborn, S.*
AU  - Söderberg, M.*
AU  - Mattsson, S.*
AU  - Hoeschen, C.
AU  - Cantone, M.-C.*
C1  - 7540
C2  - 29783
SP  - 985-993
TI  - A compartmental model for biokinetics and dosimetry of 18F-choline in prostate cancer patients.
JO  - J. Nucl. Med.
VL  - 53
IS  - 6
PB  - Society of Nuclear Medicine
PY  - 2012
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumor-targeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. METHODS: Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab and anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their (89)Zr-labeled radioactive counterparts for PET was determined in human xenograft-bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. RESULTS: Tumor-to-background ratios, with fluorescent imaging, were 1.93 ± 0.40 for bevacizumab and 2.92 ± 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. CONCLUSION: NIR fluorescence-labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence-labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.
AU  - Terwisscha van Scheltinga, A.G.*
AU  - van Dam, G.M.*
AU  - Nagengast, W.B.*
AU  - Ntziachristos, V.
AU  - Hollema, H.*
AU  - Herek, J.L.*
AU  - Schröder, C.P.*
AU  - Kosterink, J.G.*
AU  - Lub-de, Hoog, M.N.*
AU  - de Vries, E.G.*
C1  - 5456
C2  - 29093
SP  - 1778-1785
TI  - Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies.
JO  - J. Nucl. Med.
VL  - 52
IS  - 11
PB  - Society of Nuclear Medicine
PY  - 2011
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - PET and PET/CT have changed the diagnostic algorithm in oncology. Health care systems worldwide have recently approved reimbursement for PET and PET/CT for staging of non-small cell lung cancer and differential diagnosis of solitary pulmonary nodules because PET and PET/CT have been found to be cost-effective for those uses. Additional indications that are covered by health care systems in the United States and several European countries include staging of gastrointestinal tract cancers, breast cancer, malignant lymphoma, melanoma, and head and neck cancers. Regarding these indications, diagnostic effectiveness and superiority over conventional imaging modalities have been shown, whereas cost-effectiveness has been demonstrated only in part. This article reports on the current knowledge of economic evaluations of PET and PET/CT in oncologic applications. Because more economic evaluations are needed for several clinical indications, we also report on the methodologies for conducting economic evaluations of diagnostic tests and suggest an approach toward the implementation of these tests in future clinical studies.
AU  - Buck, A.K.*
AU  - Herrmann, K.*
AU  - Stargardt, T.
AU  - Dechow, T.*
AU  - Krause, B.J.*
AU  - Schreyögg, J.
C1  - 5910
C2  - 27445
SP  - 401-412
TI  - Economic evaluation of PET and PET/CT in oncology: Evidence and methodologic approaches.
JO  - J. Nucl. Med.
VL  - 51
IS  - 3
PB  - Society of Nuclear Medicine, Inc.
PY  - 2010
SN  - 0161-5505
ER  - 

TY  - JOUR
AB  - Although the diagnostic effectiveness of integrated PET/CT for staging of non-small cell lung cancer (NSCLC) has already been proven, it remains to be determined if tumor staging with combined metabolic and anatomic imaging is also cost-effective. The objective of this study was to evaluate from a payers' perspective the cost-effectiveness of staging NSCLC with CT alone (representing the mainstay diagnostic test) and with integrated PET/CT. The study is based on 172 NSCLC patients from a prospective clinical study who underwent diagnostic, contrast-enhanced helical CT and integrated PET/CT. Imaging was performed at the University Hospital Ulm between May 2002 and December 2004. To calculate treatment costs, we differentiated among cost for diagnosis, cost for nonsurgical treatment according to the clinical diagnosis, and cost for surgical procedures according to the clinical tumor stage. The diagnostic effectiveness in terms of correct TNM staging was 40% (31/77) for CT alone and 60% (46/77) for PET/CT. For the assessment of resectability (tumor stages Ia-IIIa vs. IIIb-IV), 65 of 77 patients (84%) were staged correctly by PET/CT (CT alone, 70% [54/77]). The incremental cost-effectiveness ratios per correctly staged patient were $3,508 for PET/CT versus CT alone. The incremental cost-effectiveness ratios per quality-adjusted life year gained were $79,878 for PET/CT vs. CT alone, decreasing to $69,563 assuming a reduced loss of utility (0.10 quality-adjusted life years) due to surgical morbidity.Cost-effectiveness analyses showed that costs for PET/CT are within the commonly accepted range for diagnostic tests or therapies. Therefore, reimbursement of PET/CT for NSCLC staging can be also recommended from an economic point of view.
AU  - Schreyögg, J.
AU  - Weller, J.
AU  - Stargardt, T.*
AU  - Herrmann, K.*
AU  - Bluemel, C.*
AU  - Dechow, T.*
AU  - Glatting, G.*
AU  - Krause, B.J.*
AU  - Mottaghy, F.*
AU  - Reske, S.N.*
AU  - Buck, A.K.*
C1  - 3672
C2  - 27853
SP  - 1668-1675
TI  - Cost-effectiveness of hybrid PET/CT for staging of non-small cell lung cancer.
JO  - J. Nucl. Med.
VL  - 51
IS  - 11
PB  - Soc. Nuclear Medicine Inc.
PY  - 2010
SN  - 0161-5505
ER  -