Lu-DOTA-coupled minigastrin peptides: promising theranostic agents in neuroendocrine cancers.

Treatment with radionuclide labeled regulatory peptides is a promising tool in the management of patients with inoperable receptor positive neuroendocrine tumors. Peptide receptor lutetium-177 radionuclide therapy currently has gained ample attention due to high specific accumulation of regulatory peptides at tumor cell surface and promising characteristics of β- and γ-energy photons of lutetium-177 radionuclide. In this study gastrin peptides analogues were labeled with lutetium-177 by subsequent mixing of LuCl (~ 185 MBq), ammonium acetate buffer of 5 pH, gentistic acid, aqueous solution of gastrin peptide analogues (1 mg/mL) and heating the reaction mixture at 98 °C which resulted in high radiochemical yield (> 96%). Chromatographic analysis was carried out to analyze the radiochemical purity. The shelf life and serum stability results showed the labeled peptides are sufficiently stable up to 4-h. Glomerular filtration rate study results showed moderate filtration through kidneys. The GFR values of Lu-MGCL2 and Lu-MGCL4 was noted 48 mL/min and 45 mL/min, respectively. Biodistribution and scintigraphy study using rat and rabbit models showed minimal non-target accumulation, moderate uptake by liver and kidneys. The promising radiochemical yield, stability, GFR values and biodistribution results of Lu-MGCL2 & 4 indicate, the agents can be tested clinically for PRRT procedures.