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

Abstract

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.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…A very interesting paper (Opalinska et al 2023 ) recently reported a new advancement for imaging neuroendocrine tumours (NET) with a novel 99m Tc-radiolabelled somatostatin receptor (SSTR) antagonist ([ 99m Tc]Tc-TECANT1) (Novak et al 2023 ). The current standard for imaging NET is the SSTR agonist [ 68 Ga]Ga-DOTA-TATE/TOC.…”

Comparison of 99mTc radiolabeled somatostatin antagonist with [68 Ga]Ga-DOTA-TATE in a patient with advanced neuroendocrine tumor

“…Below (Fig. 1), we present a comparison of SPECT/CT with a SSTR antagonist [ 99m Tc]Tc-TECANT1 (N4-p-Cl-Phe-cyclo(D-Cys-Tyr-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2, where D-Aph(Cbm): D-4-amino-carbamoyl-phenylalanine) [ 3 ] and [ 68 Ga]Ga-DOTA-TATE PET/CT (EudraCT no 2019–003379-20). Please note better visualization of the lesions seen in the study with [ 99m Tc]Tc-TECANT1 (in 6 out of 7 lesions) as well as significantly higher tumor-to-background ratio (in primary and metastatic lesions) obtained with the novel tracer (measured as an absolute number of counts in lesion to background (TBR)) in comparison to [ 68 Ga]Ga-DOTA-TATE PET/CT (4,07 (range 1,36–7,58) vs 2,26 (range 1,15–3,39)).…”