Synthesis And Biological Evaluation Of Gallium Radiopharmaceuticals Compounds

Targeting the overexpressed receptors of cancerous cells may be used with great success both for early detection and treatment of many cancers. Peptide-based targeting molecules take few advantages over the antibodies and proteins: rapid blood clearance and non-target tissues, non immunogene and high tumor penetration. The high expression level of many peptide receptors on the cancer cells compared with the normal tissues is a powerfull tool for both diagnostic and targeted radiotherapy [1-3].Ga-68 is a short-lived radioisotope emitting positrons with a physical half-life of 68 min, suitable for chemical synthesis, separation and purification of the radiolabelled compounds; furthermore, the self life matches many peptides and other small molecules pharmacokinetics, characterized by rapid diffusion, localization at the target and fast blood clearance [1]. Since only 11% of this radioisotope decay proceeds through electron capture and the remaining 89% through positronic emission with energy of 1.89 MeV [4],Ga-68 is very attractive for PET (positron emission tomography) imaging applications in nuclear medicine [5, 6].The Ga-68 radiolabelling processes of different peptides were successfully adapted on the automated module, reducing reaction time and operator exposure. Nanomoles of very promising candidates for imaging targets of interest in cancer diagnosis and therapy follow-up such as neurotensin receptors, somatostatin receptors and alpha v beta 3 integrin receptors, were labelled and purified, resulting in high radiochemical purity compounds (RCP > 98%). The radiolabelling yields of Ga-68-NODAGA-NOC, Ga-68-NODAGA-RGDfK, Ga-68-DOTA-E-[c(RGDfK)(2)] were higher than 90%. The biological evaluation of Ga-68-DOTA/NODAGA-[c(RGDfK)(2)] in tumor bearing models show a high and stable tumor uptake, good tumor to background ratio and fast renal elimination of the NODAGA derivative.