The Practicality of Nanoceria-PAN-Based 68Ge/68Ga Generator Toward Preparation of 68Ga-Labeled Cyclic RGD Dimer as a Potential PET Radiotracer for Tumor Imaging

Abstract

Cyclic RGD (Arg-Gly-Asp) peptides radiolabeled with (68)Ga have great potential for the early tumor detection and noninvasive monitoring of tumor metastasis and therapeutic response. Herein, the preparation of (68)Ga-labeled DOTA-E[c(RGDfK)](2) (DOTA=1,4,7,10-tetraazacylododecane-1,4,7,10-tetracetic acid; E=Glutamic acid; R=Arginine; G=Glycine; D=Aspartic acid; f=phenyl alanine; K=lysine) using (68)Ga directly eluted from a nanoceria-polyacrylonitrile (CeO(2)-PAN)-based (68)Ge/(68)Ga generator developed in-house was reported. The (68)Ga complex of DOTA-E[c(RGDfK)](2) was synthesized with >98% radiochemical purity by incubating 20 μg of the conjugate with (68)GaCl(3) (74-111 MBq) in acetate buffer (pH 3.5-4.0) at 90°C for 10 minutes. The complex exhibited excellent in vitro stability in 0.1 M EDTA solution at room temperature upto 1 hour studied (radiochemical purity: 98.0%). The biological efficacy of the radiolabeled conjugate was studied in C57/BL6 mice bearing melanoma tumors. The results of the biodistribution studies revealed significant tumor uptake (4.14±0.54%ID/g) within 10 minutes postinjection (p.i.), which increased further to 4.61±0.31%ID/g at 30 minutes p.i. The tumor-to-blood ratio was found to increase from 1.75±0.42 at 10 minutes p.i. to 2.25±0.20 at 60 minutes p.i., whereas the tumor-to-liver and tumor-to-muscle ratio between the same time points increased from 2.71±0.76 to 3.31±0.84 and 5.37±1.08 to 8.97±1.32, respectively. The study successfully demonstrated the preparation of (68)Ga-DOTA-E[c(RGDfK)](2) as a potential positron-emission tomography radiotracer for possible use in tumor imaging by using (68)Ga eluted from a reliable, easy-to-handle (68)Ge/(68)Ga generator developed in-house, without any postelution purification of (68)Ga.