S Ghiani1, I Hawala2, D Szikra3,4, G Trencsényi3,4, Z Baranyai5, G Nagy3, A Vágner3, R Stefania2, S Pandey6, A Maiocchi7. 1. Bracco Research Centre, Bracco Imaging SpA, Via Ribes 5, 10010, Colleretto Giacosa (TO), Italy. simona.ghiani@bracco.com. 2. Dipartimento di Biotecnologie Molecolari e Scienze per la salute, Centro di Imaging Molecolare, Università degli Studi di Torino, Via Nizza 52, 10126, Torino, Italy. 3. Scanomed Ltd., Nagyerdei krt. 98, Debrecen, 4032, Hungary. 4. Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary. 5. Bracco Research Centre, Bracco Imaging SpA, Via Ribes 5, 10010, Colleretto Giacosa (TO), Italy. 6. Bracco Research USA Inc., 259 Prospect Plains Rd., Bldg. H, Monroe Township, NJ, 08831, USA. 7. Bracco SpA, Via Caduti di Marcinelle, 13, 20134, Milan, Italy.
Abstract
PURPOSE: The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. BACKGROUND: Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]- and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)]. RESULTS: B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. CONCLUSIONS: This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.
PURPOSE: The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. BACKGROUND: Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]- and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)]. RESULTS: B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. CONCLUSIONS: This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.
Authors: Martina Benešová; Ulrike Bauder-Wüst; Martin Schäfer; Karel D Klika; Walter Mier; Uwe Haberkorn; Klaus Kopka; Matthias Eder Journal: J Med Chem Date: 2016-03-01 Impact factor: 7.446
Authors: Il Minn; Ying Chen; Ana P Kiess; Robert Hobbs; George Sgouros; Ronnie C Mease; Mrudula Pullambhatla; Colette J Shen; Catherine A Foss; Martin G Pomper Journal: J Nucl Med Date: 2015-07-16 Impact factor: 10.057
Authors: Valery Radchenko; Jonathan W Engle; Dmitri G Medvedev; Joel M Maassen; Cleo M Naranjo; George A Unc; Catherine A L Meyer; Tara Mastren; Mark Brugh; Leonard Mausner; Cathy S Cutler; Eva R Birnbaum; Kevin D John; F Meiring Nortier; Michael E Fassbender Journal: Nucl Med Biol Date: 2017-04-07 Impact factor: 2.408
Authors: K P Maresca; S M Hillier; F J Femia; D Keith; C Barone; J L Joyal; C N Zimmerman; A P Kozikowski; J A Barrett; W C Eckelman; J W Babich Journal: J Med Chem Date: 2009-01-22 Impact factor: 7.446
Authors: Joachim Pfister; Dominik Summer; Christine Rangger; Milos Petrik; Elisabeth von Guggenberg; Paolo Minazzi; Giovanni B Giovenzana; Luigi Aloj; Clemens Decristoforo Journal: EJNMMI Res Date: 2015-12-15 Impact factor: 3.138
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