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

Broad availability and cost-effectiveness of Mo-99/Tc-99m generators worldwide support the use, and thus the development, of novel Tc-99m-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 Tc-99m-labelled SST2 antagonist, [Tc-99m]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 [Tc-99m]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 mu g. In conclusion, [Tc-99m]Tc-TECANT-1 is suitable to be advanced into a first-in-human clinical trial.

Automated summary

The broad availability and cost-effectiveness of Mo-99/Tc-99m generators worldwide have supported the use and development of novel Tc-99m-labelled radiopharmaceuticals. This study aimed to provide a reliable method for the facile preparation of a Tc-99m-labelled SST2 antagonist, [Tc-99m]Tc-TECANT-1, in a hospital radiopharmacy setting for a multi-centre clinical trial. A freeze-dried three-vial kit was successfully developed to ensure successful and reproducible on-site preparation of the radiopharmaceutical for human use shortly before administration.