Development of the 99mTc-Labelled SST2 Antagonist TECANT-1 for a First-in-Man Multicentre Clinical Study

Autor: Doroteja Novak, Barbara Janota, Anton Amadeus Hörmann, Agnieszka Sawicka, Marko Kroselj, Alicja Hubalewska-Dydejczyk, Melpomeni Fani, Renata Mikolajczak, Petra Kolenc, Clemens Decristoforo, Piotr Garnuszek
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceutics, 16 str. : Ilustr., Vol. 15, iss. 3, art. 885, 2023
COBISS-ID: 517949977
Pharmaceutics, vol. 15, no. 3, 885, 2023.
Pharmaceutics; Volume 15; Issue 3; Pages: 885
ISSN: 1999-4923
Popis: 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. Nasl. z nasl. zaslona. Opis vira z dne 9. 3. 2023. Št. članka: 885. Bibliografija: str. 15-16. Abstract. ERA PerMed, Novel 99mTc-labelled somatostatin receptor antagonists in the diagnostic algorithm of neuroendocrine neoplasms—a feasibility study” (TECANT), TECANT Austrian Science Fund FWF National Centre for Research and Development Jagiellonian University Medical College National Centre for Nuclear Research, MIZS (Ministry of Education, Science and Sport), Razvoj inovativnega, z gama sevalcem tehnecijem-99m označenega antagonista somatostatinskih receptorjev za diagnostiko nevroendokrinih novotvorb - raziskava izvedljivosti, TECANT
Databáze: OpenAIRE
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