18-F-Fluoroglucosylation of an arginine-arginine-leucine peptide as a potential tumor imaging agent for positron emission tomography

Based on the principle of oxime formation, 18F labeling of polypeptides can be achieved via a reaction between an aldehyde group-containing 18F-prosthetic group and an aminooxy-modified polypeptide. The focus of this study was to investigate the one-step synthesis of 2-[18F] fluoro-2-deoxyglucose (18F-FDG)- arginine-arginine-leucine (RRL) from open-ring 18F-FDG and the aminooxy-modified RRL peptide cyclo(RRLfK)-ONH2 and to study the biological distribution of 18F-FDG-RRL in a nude mouse model of human neuroglioma.

The aminooxy-modified RRL peptide cyclo(RRLfK)-ONH2 was used as the precursor to react with 18F-FDG at 100 ℃ and different pH values for 30 minutes to synthesize 18F-FDG-RRL. The labeling yield, radiochemical purity, and in-vitro stability of the product were measured, and the biological distribution of 18F-FDG-RRL in tumor-bearing nude mice was analyzed at 30 minutes, 60 minutes and 120 minutes.

The labeling yield of 18F-FDG-RRL was (25.5±5.0) % at a pH of 2.0, and its radiochemical purity was greater than 95%. 18F-FDG-RRL was mainly excreted through the kidneys, with rapid blood clearance. One hour after injection, the uptake of 18F-FDG-RRL in tumors was (1.83±0.12) injected dose per gram of tissue (%ID/g), with a tumor/muscle ratio of 7.03±0.04, a tumor/blood ratio of 4.36±0.21 and a tumor/brain ratio of 7.53±1.37.

The synthesis of 18F-FDG-RRL can be achieved through oximation. This method is straightforward and easy to promote. 18F-FDG-RRL has rapid blood clearance and high uptake by tumors.