Simon Lindner1, Marcel Simmet2, Franz Josef Gildehaus2, Klaus Jurkschat3, Carmen Wängler4, Björn Wängler5, Peter Bartenstein2, Ralf Schirrmacher6, Harun Ilhan2. 1. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. Electronic address: Simon.Lindner@med.uni-muenchen.de. 2. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. 3. Fakultät für Chemie und Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4. Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany. 5. Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany. 6. Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, Alberta, Canada.
Abstract
INTRODUCTION: [18F]SiTATE (formerly known as [18F]SiFAlin-TATE) was recently introduced as a highly promising imaging agent for the diagnosis of well-differentiated neuroendocrine tumors (NET) using positron emission tomography/computed tomography (PET/CT). A high tumor uptake and excellent image quality, the straightforward labeling approach, as well as the economic and logistic advantages of 18F- over 68Ga-labeled compounds predestinate [18F]SiTATE to become a potential new clinical reference standard. A novel state-of-the-art methodology of automated radiopharmaceutical production is required to establish [18F]SiTATE in clinical routine. This work illustrates the development of a novel synthesis procedure of [18F]SiTATE on an automated synthesis unit (ASU) and the clinical applicability of the tracer in human NET imaging. METHODS: A new synthesis protocol was generated for the production of [18F]SiTATE on the Scintomics GRP™ platform for clinical NET imaging. The synthesis was carried out according to common Good Manufacturing Practice (GMP) guidelines including all quality control measurements. To confirm utility, clinical batches (n = 3) were produced and applied to six patients diagnosed with NET. RESULTS: [18F]SiTATE was obtained in 54 ± 4% (n = 3) non-decay corrected radiochemical yield (RCY), with a radiochemical purity of 96.3 ± 0.1% and a molar activity (Am) of 472 ± 45 GBq/μmol (n = 3). Quality control measurements always met the local release criteria. All specifications were taken or adapted from the Ph.Eur. regulations. PET/CT imaging with [18F]SiTATE produced on the GRP™ module confirmed the expected high image quality. The in vivo distribution pattern and excellent tumor to non-tumor contrast observed, matched the quality of the manually prepared [18F]SiTATE batches. CONCLUSIONS: The automated manufacture of [18F]SiTATE was developed using the Scintomics GRP™ platform. The high quality of the radiotracer matched stringent quality control requirements adhering to common GMP guidelines, and its clinical applicability was confirmed by human PET/CT investigations. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: The automated process for the manufacture of [18F]SiTATE described herein represents an important contribution to make [18F]SiTATE routinely accessible for its use in clinical NET diagnosis.
INTRODUCTION: [18F]SiTATE (formerly known as [18F]SiFAlin-TATE) was recently introduced as a highly promising imaging agent for the diagnosis of well-differentiated neuroendocrine tumors (NET) using positron emission tomography/computed tomography (PET/CT). A high tumor uptake and excellent image quality, the straightforward labeling approach, as well as the economic and logistic advantages of 18F- over 68Ga-labeled compounds predestinate [18F]SiTATE to become a potential new clinical reference standard. A novel state-of-the-art methodology of automated radiopharmaceutical production is required to establish [18F]SiTATE in clinical routine. This work illustrates the development of a novel synthesis procedure of [18F]SiTATE on an automated synthesis unit (ASU) and the clinical applicability of the tracer in human NET imaging. METHODS: A new synthesis protocol was generated for the production of [18F]SiTATE on the Scintomics GRP™ platform for clinical NET imaging. The synthesis was carried out according to common Good Manufacturing Practice (GMP) guidelines including all quality control measurements. To confirm utility, clinical batches (n = 3) were produced and applied to six patients diagnosed with NET. RESULTS: [18F]SiTATE was obtained in 54 ± 4% (n = 3) non-decay corrected radiochemical yield (RCY), with a radiochemical purity of 96.3 ± 0.1% and a molar activity (Am) of 472 ± 45 GBq/μmol (n = 3). Quality control measurements always met the local release criteria. All specifications were taken or adapted from the Ph.Eur. regulations. PET/CT imaging with [18F]SiTATE produced on the GRP™ module confirmed the expected high image quality. The in vivo distribution pattern and excellent tumor to non-tumor contrast observed, matched the quality of the manually prepared [18F]SiTATE batches. CONCLUSIONS: The automated manufacture of [18F]SiTATE was developed using the Scintomics GRP™ platform. The high quality of the radiotracer matched stringent quality control requirements adhering to common GMP guidelines, and its clinical applicability was confirmed by human PET/CT investigations. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: The automated process for the manufacture of [18F]SiTATE described herein represents an important contribution to make [18F]SiTATE routinely accessible for its use in clinical NET diagnosis.
Authors: Silvio Aime; Mohammed Al-Qahtani; Martin Behe; Guy Bormans; Giuseppe Carlucci; Jean N DaSilva; Clemens Decristoforo; Adriano Duatti; Philip H Elsinga; Klaus Kopka; Xiang-Guo Li; Zhibo Liu; Robert H Mach; Oskar Middel; Jan Passchier; Marianne Patt; Ivan Penuelas; Ana Rey; Peter J H Scott; Sergio Todde; Jun Toyohara; Danielle Vugts; Zhi Yang Journal: EJNMMI Radiopharm Chem Date: 2021-03-18
Authors: Alexander Wurzer; Daniel Di Carlo; Michael Herz; Antonia Richter; Stephanie Robu; Ralf Schirrmacher; Alba Mascarin; Wolfgang Weber; Matthias Eiber; Markus Schwaiger; Hans-Juergen Wester Journal: EJNMMI Radiopharm Chem Date: 2021-01-23
Authors: Carmen Wängler; Leonie Beyer; Peter Bartenstein; Björn Wängler; Ralf Schirrmacher; Simon Lindner Journal: EJNMMI Radiopharm Chem Date: 2022-09-05
Authors: Leonie Beyer; Astrid Gosewisch; Simon Lindner; Friederike Völter; Lena M Mittlmeier; Reinhold Tiling; Matthias Brendel; Clemens C Cyran; Marcus Unterrainer; Johannes Rübenthaler; Christoph J Auernhammer; Christine Spitzweg; Guido Böning; F J Gildehaus; Klaus Jurkschat; Carmen Wängler; Björn Wängler; Ralf Schirrmacher; Vera Wenter; Andrei Todica; Peter Bartenstein; Harun Ilhan Journal: Eur J Nucl Med Mol Imaging Date: 2021-04-29 Impact factor: 9.236