Speaker
Description
Our goal is to contribute for the development of new strategies for prostate cancer theranostics, based on bombesin (BBN) analogues with very high affinity and specificity for the GRP receptor (GRPr) and on a multistep pretargeting strategy. To achieve this goal, we have opted by in vivo inverse-electron demand Diels-Alder (IEDDA) reactions between BBN antagonists carrying a trans-cyclooctene (TCO) bioorthogonal reactive group and recognizing the GRPr that is overexpressed at the surface of tumor cells and clickable tetrazine-containing radiocomplexes. We have hypothesized that the prior administration of a non-radioactive antagonist, followed by the injection of a clickable radioactive complex with optimized pharmacokinetics, can be an efficient alternative to spare the kidneys from unwanted radiation effects, which often represent an obstacle in Peptide Receptor Radionuclide Therapy (PRRT).
In this communication, we will report on the radiosynthesis, biodistribution, pharmacokinetics and in vitro/in vivo stability of a small family of tetrazine-containing 111In-DOTA and 111In-DOTAGA complexes, as well as on their use for the in vitro labeling of a BBN antagonist carrying a TCO moiety linked to the peptide through different linkers. Cellular uptake studies of the resulting radioconjugates in human prostate cancer PC3 cells will be also presented, including blockade experiments with cold BBN analogues. These studies are expected to identify the best-performing clickable DOTA or DOTAGA chelator and BBN antagonist for further in vivo evaluation within the pretargeting strategy and using 177Lu as a trivalent therapeutic radiometal suitable for PRRT.
