Our project is focused on bispecific targeting of prostate cancer cells. We are evaluating a heterodimer which includes PSMA-617 and DOTA-RM2 in its structure and targets both Prostate-Specific Membrane Antigen (PSMA) and Gastrin- Releasing Peptide Receptors (GRPr) (receptors that exist on prostate cancer cells). All three molecules, the heterodimer and both monomers, are radiolabeled with the diagnostic radionuclide Ga-68 and show high labeling levels (>93%). We are performing internalization assays, specific binding and inhibition potency assays (by calculation of IC50). Two different types of cells are used in these in vitro assays, LNCaP (PSMA+, GRPr -) and PC3 (PSMA-, GRPr+). Our future project involves biodistribution studies on healthy experimental animals and pathological tumor models bearing LNCaP and PC3 tumors.
Gold nanoparticles, have been found highly effective in cancer diagnosis and therapy, due to their own physicochemical properties, easy functionalization of their surface with different chemical entities, low toxicity and biocompatibility. On the other hand 99mTc is used due to the emission of low energy γ-rays (140keV), suitable half-life (6.02 h) and good availability from 99Mo/99mTc generators. The aim of the study, is to radiolabel Gold Nanoparticles (AuNPs) of different sizes with thiol ligands (as an anchor for AuNPs surface) that allow direct labeling with 99mTc-carbonyls. Thiols are the most important type of stabilizing molecules for AuNPs of any size because thiols lead to the formation of strong Au-S bonds. After functionalization and radiolabeling of the AuNPs, we perform in vitro stability studies in human serum as well as in cysteine and histidine solutions, in order to evaluate their stability in vivo. Furthermore, cytotoxicity studies to invest the potential toxic effect of the formed complexes, as well as biodistribution studies in tumor-bearing animal models, are carried out.