20.500.12556/RUL-144722 Development of the 99mTc-labelled SST2 antagonist TECANT-1 for a first-in-man multicentre clinical study Broad availability and cost-effectiveness of 99Mo/99mTc generators worldwide support the use, and thus the development, of novel 99mTc-labelled radiopharmaceuticals. In recent years, preclinical and clinical developments for neuroendocrine neoplasms patient management focused on somatostatin receptor subtype 2 (SST2) antagonists, mainly due to their superiority in SST2-tumour targeting and improved diagnostic sensitivity over agonists. The goal of this work was to provide a reliable method for facile preparation of a 99mTc-labelled SST2 antagonist, [99mTc]Tc-TECANT-1, in a hospital radiopharmacy setting, suitable for a multi-centre clinical trial. To ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration, a freeze-dried three-vial kit was developed. The final composition of the kit was established based on the radiolabelling results obtained during the optimisation process, in which variables such as precursor content, pH and buffer, as well as kit formulations, were tested. Finally, the prepared GMP-grade batches met all predefined specification parameters together with long-term kit stability and stability of the product [99mTc]Tc-TECANT-1. Furthermore, the selected precursor content complies with micro-dosing, based on an extended single-dose toxicity study, where histopathology NOEL was established at 0.5 mg/kg BW, being more than 1000 times higher than the planned human dose of 20 µg. In conclusion, [99mTc]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial. technetium-99m somatostatin receptor antagonists kit formulation single dose toxicity SPECT radiopharmaceuticals neuroendocrine neoplasms tehnecij-99m antagonisti receptorjev somatostatina formulacija kompleta toksičnost enkratnega odmerka SPECT radiofarmacevtiki nevroendokrine neoplazme radiofarmacija true false true Angleški jezik Slovenski jezik Članek v reviji 2023-03-09 13:11:06 2023-03-09 13:11:12 2023-03-10 03:35:49 0000-00-00 00:00:00 2023 0 0 16 str. iss. 3, ǂart. ǂ885 Vol. 15 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.849.2 1999-4923 10.3390/pharmaceutics15030885 144626179 pharmaceutics-15-00885.pdf pharmaceutics-15-00885.pdf 1 EB3212DAA9F8AD74C5A8EB03D8258C09 7a65a08ae78436bf068319d1ba5e3be7409e68e0642d991888af2e690d66141a d8a29c23-be74-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167202 https://www.mdpi.com/1999-4923/15/3/885 1 73585dc0-be73-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167199 Fakulteta za farmacijo 0 0 0