TY - JOUR AB - Background: Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. Methods: Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. Results: All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. Conclusions: In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting. AU - Roll, W.* AU - Müther, M.* AU - Böning, G.* AU - Delker, A.* AU - Warneke, N.* AU - Gildehaus, F.J.* AU - Schäfers, M.* AU - Stummer, W.* AU - Zeidler, R. AU - Reulen, H.J.* AU - Stegger, L.* C1 - 68328 C2 - 54747 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: A pilot study. JO - EJNMMI Res. VL - 13 IS - 1 PB - Springer PY - 2023 SN - 2191-219X ER - TY - JOUR AB - BACKGROUND: Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett's esophagus. METHODS: Six L2-IL1B mice with advanced stage of disease (12-16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12-14 months old)  by a novel imaging system with two L2-IL1B mice used as negative controls. RESULTS: Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells  by confocal microscopy further confirmed the imaging results. CONCLUSIONS: This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett's esophagus. Further investigations are needed to assess its use in the clinical setting. AU - Marcazzan, S. AU - Braz Carvalho, M.J.* AU - Konrad, M.* AU - Strangmann, J.* AU - Tenditnaya, A. AU - Baumeister, T.* AU - Schmid, R.M.* AU - Wester, H.J.* AU - Ntziachristos, V. AU - Gorpas, D. AU - Wang, T.C.* AU - Schottelius, M.* AU - Quante, M.* C1 - 63993 C2 - 52038 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett's esophagus. JO - EJNMMI Res. VL - 12 IS - 1 PB - Springer PY - 2022 SN - 2191-219X ER - TY - JOUR AB - Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-D-glucose (18FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed. AU - Han, J.* AU - Harrison, L. AU - Patzelt, L.* AU - Wu, M.* AU - Junker, D.* AU - Herzig, S. AU - Berriel Diaz, M. AU - Karampinos, D.C.* C1 - 63116 C2 - 51327 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - Imaging modalities for diagnosis and monitoring of cancer cachexia. JO - EJNMMI Res. VL - 11 IS - 1 PB - Springer PY - 2021 SN - 2191-219X ER - TY - JOUR AB - Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats. AU - Mohr, H. AU - Foscarini, A. AU - Steiger, K.* AU - Ballke, S.* AU - Rischpler, C.* AU - Schilling, F.* AU - Pellegata, N.S. C1 - 63777 C2 - 51754 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - Imaging pheochromocytoma in small animals: Preclinical models to improve diagnosis and treatment. JO - EJNMMI Res. VL - 11 IS - 1 PB - Springer PY - 2021 SN - 2191-219X ER - TY - JOUR AB - Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments differentiate in protein/lipid glycosylation patterns and analyze differences in glycan fragments in those compartments with clinicopathologic correlates. Results: We analyzed native glycan fragments in 109 human FFPE PDAC samples using high mass resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT-ICR-MSI). Our method allows detection of native glycan fragments without previous digestion with PNGase or any other biochemical reaction. With this method, 8 and 18 native glycans were identified as uniquely expressed in only stromal or only cancer cell compartment, respectively. Kaplan–Meier survival model identified glycan fragments that are expressed in cancer cell or stromal compartment and significantly associated with patient outcome. Among cancer cell region-specific glycans, 10 predicted better and 6 worse patient survival. In the stroma, 1 glycan predicted good and 4 poor patient survival. Using factor analysis as a dimension reduction method, we were able to group the identified glycans in 2 factors. Multivariate analysis revealed that these factors can be used as independent survival prognostic elements with regard to the established Union for International Cancer Control (UICC) classification both in tumor and stroma regions. Conclusion: Our method allows in situ detection of naturally occurring glycans in FFPE samples of human PDAC tissue and highlights the differences among glycans found in stromal and cancer cell compartment offering a basis for further exploration on the role of specific glycans in cancer–stroma communication. AU - Sun, N. AU - Trajkovic-Arsic, M.* AU - Li, F. AU - Wu, Y. AU - Münch, C.* AU - Kunzke, T. AU - Feuchtinger, A. AU - Steiger, K.* AU - Schlitter, A.M.* AU - Weichert, W.* AU - Esposito, I.* AU - Siveke, J.T.* AU - Walch, A.K. C1 - 63701 C2 - 51616 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma. JO - EJNMMI Res. VL - 11 IS - 1 PB - Springer PY - 2021 SN - 2191-219X ER - TY - JOUR AB - The glucagon receptor (GCGR) is emerging as an important target in anti-diabetic therapy, especially as part of the pharmacology of dual glucagon-like peptide-1/glucagon (GLP-1/GCG) receptor agonists. However, currently, there are no suitable biomarkers that reliably demonstrate GCG receptor target engagement.MethodsTwo potent GCG receptor peptide agonists, S01-GCG and S02-GCG, were labeled with positron emission tomography (PET) radionuclide gallium-68. The GCG receptor binding affinity and specificity of the resulting radiopharmaceuticals [Ga-68]Ga-DO3A-S01-GCG and [Ga-68]Ga-DO3A-S02-GCG were evaluated in HEK-293 cells overexpressing the human GCG receptor and on frozen hepatic sections from human, non-human primate, and rat. In in vivo biodistribution, binding specificity and dosimetry were assessed in rat.Results[Ga-68]Ga-DO3A-S01-GCG in particular demonstrated GCG receptor-mediated binding in cells and liver tissue with affinity in the nanomolar range required for imaging. [Ga-68]Ga-DO3A-S01-GCG binding was not blocked by co-incubation of a GLP-1 agonist. In vivo binding in rat liver was GCG receptor specific with low non-specific binding throughout the body. Moreover, the extrapolated human effective doses, predicted from rat biodistribution data, allow for repeated PET imaging potentially also in combination with GLP-1R radiopharmaceuticals.Conclusion[Ga-68]Ga-DO3A-S01-GCG thus constitutes a first-in-class PET tracer targeting the GCG receptor, with suitable properties for clinical development. This tool has potential to provide direct quantitative evidence of GCG receptor occupancy in humans. AU - Velikyan, I.* AU - Haack, T.* AU - Bossart, M.* AU - Evers, A.* AU - Laitinen, I.* AU - Larsen, P.* AU - Plettenburg, O. AU - Johansson, L.* AU - Pierrou, S.* AU - Wagner, M.* AU - Eriksson, O.* C1 - 55558 C2 - 46230 CY - Campus, 4 Crinan St, London, N1 9xw, England TI - First-in-class positron emission tomography tracer for the glucagon receptor. JO - EJNMMI Res. VL - 9 PB - Springeropen PY - 2019 SN - 2191-219X ER - TY - JOUR AB - BACKGROUND: Tumor targeting is of high clinical and biological relevance, and major efforts have been made to develop molecular imaging technologies for visualization of the disease markers in tissue. Of particular interest is apoptosis which has a profound role within tumor development and has significant effect on cancer malignancy. METHODS: Herein, we report on targeting of phosphatidylserine-exposing cells within live tumor allograft models using a synthetic near infrared zinc(II)-dipicolylamine probe. Visualization of the probe biodistribution is performed with whole body multispectral optoacoustic tomography (MSOT) system and subsequently compared to results attained by planar and tomographic fluorescence imaging systems. RESULTS: Compared to whole body optical visualization methods, MSOT attains remarkably better imaging capacity by delivering high-resolution scans of both disease morphology and molecular function in real time. Enhanced resolution of MSOT clearly showed that the probe mainly localizes in the vessels surrounding the tumor, suggesting that its tumor selectivity is gained by targeting the phosphatidylserine exposed on the surface of tumor vessels. CONCLUSIONS: The current study demonstrates the high potential of MSOT to broadly impact the fields of tumor diagnostics and preclinical drug development. AU - Bühler, A. AU - Herzog, E. AU - Ale, A.B.F AU - Smith, B.D.* AU - Ntziachristos, V. AU - Razansky, D. C1 - 7415 C2 - 29711 SP - 1-6 TI - High resolution tumor targeting in living mice by means of multispectral optoacoustic tomography. JO - EJNMMI Res. VL - 2 IS - 1 PB - Springer PY - 2012 SN - 2191-219X ER -