Speaker
Description
Pre-targeting approaches based on the inverse-electron-demand Diels-Alder (iEDDA) reaction between strained trans-cyclooctenes (TCO) and electron-deficient tetrazines (Tz) have emerged in recent years as valid alternatives to classic targeted strategies to improve the diagnostic and therapeutic properties of radioactive probes. As reported in this communication, we have synthesized a small family of clickable chelators and proceeded with their labeling with medically relevant radiometals (e.g. 111In, 177Lu and 90Y) to explore pre-targeting strategies, based on in vivo click chemistry [1]. In particular, the [90Y]Y-DOTA-Tz complex was evaluated in a prostate cancer PC3 xenograft by ex-vivo biodistribution studies and Cerenkov luminescence imaging (CLI). The studies comprised the injection of a clickable bombesin (BBN) antagonist in the tumour-bearing mice followed by the radiocomplex [90Y]Y-DOTA-Tz, and the mice imaged by CLI at different post-injection times (p.i.). Analysis of the images 15 min and 1 h p.i. pointed out an encouraging quick tumour uptake with a fast washout, providing a preliminary proof of concept of the usefulness of the designed clickable complexes for pre-targeting strategies. To the best of our knowledge, the use of peptide antagonists for this purpose was not explored before. However, further investigations are needed to optimize the pre-targeting approach based on this type of biomolecules and evaluate its eventual advantages.
[1] Alice D’Onofrio et al., Frontiers in Medicine 8, 647379 (2021).
