Preparation and preclinical evaluation of66 Ga-DOTA-E(c(RGDfK))2 as a potential theranostic radiopharmaceutical

Abstract Introduction Integrin αv β3 plays an important role in angiogenesis and is over-expressed in tumoral endothelial cells and some other tumor cells. RGD (Arg-Gly-Asn) peptides labeled with68 Ga (t1/2 = 68 min) have showed good characteristics for imaging of αv β3 expression using positron emission tomography (PET). Gallium-66 has been proposed as a PET imaging alternative to68 Ga and given the unique high energy of its emitted positrons (Emax 4.15 MeV) it may also be useful for therapy. The aim of this research is to prepare [66 Ga]DOTA-E-[c(RGDfK)]2 and evaluate in mice its potential as a new theranostic radiopharmaceutical. Methods High specific activity66 Ga was produced via the66 Zn(p,n) reaction, and the labelling method of DOTA-E-[c(RGDfK)]2 with66 Ga was optimized. Radiochemical purity was determined by TLC, and in vitro stability and protein binding were determined. Serial microPET imaging and biodistribution studies were carried out in nude mice bearing C6 xenografts. Radiation absorbed dose estimates were based on the biodistribution studies, where tumor and organs of interest were collected at 0.5, 1, 3, 5 and 24 h post-injection of [66 Ga]DOTA-E-[c(RGDfK)]2. Results Our results have shown that [66 Ga]DOTA-E-[c(RGDfK)]2 can be prepared with high radiochemical purity (>97%), specific activity (36–67 GBq/μmol), in vitro stability, and moderate protein binding. MicroPET imaging up to 24 post-injection showed contrasting tumors reflecting αv β3 -targeted tracer accumulation. Biodistribution studies and dosimetry estimations showed a stable tumor uptake, rapid blood clearance, and favorable tumor-to-tissue ratios. Conclusions The peptide conjugated DOTA-E-[c(RGDfK)]2 labeled with66 Ga may be attractive as a theranostic agent for tumors over-expressing αv β3 integrins.