Development of the 99mTc-labelled SST2 antagonist TECANT-1 for a first-in-man multicentre clinical study

Novak, Doroteja (author), Janota, Barbara (author), Hörmann, Anton Amadeus (author), Sawicka, Agnieszka (author), Krošelj, Marko (author), Hubalewska-Dydejczyk, Alicja (author), Fani, Melpomeni (author), Mikolajczak, Renata (author), Kolenc, Petra (author), Decristoforo, Clemens (author), Garnuszek, Piotr (author)

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.

• Language: English
• Keywords: technetium-99m, somatostatin receptor antagonists, kit formulation, single dose toxicity, SPECT, radiopharmaceuticals, neuroendocrine neoplasms
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 16 str.
• Numbering: Vol. 15, iss. 3, ǂart. ǂ885
• PID: 20.500.12556/RUL-144722
• UDC: 615.849.2
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics15030885
• COBISS.SI-ID: 144626179
• Publication date in RUL: 09.03.2023

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: tehnecij-99m, antagonisti receptorjev somatostatina, formulacija kompleta, toksičnost enkratnega odmerka, SPECT, radiofarmacevtiki, nevroendokrine neoplazme, radiofarmacija