The Radiolabeling of a Gly-Sar Dipeptide Derivative with Flourine-18 and Its Use as a Potential Peptide Transporter PET Imaging Agent

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-02, Vol.25 (3), p.643
• Main Authors: Molotkov, Andrei, Castrillon, John W, Santha, Sreevidya, Harris, Paul E, Leung, David K, Mintz, Akiva, Carberry, Patrick
• Format: Article
• Language: English
• Subjects: Advantages; Carbon; Computed tomography; Fluorides; Fluorine; Fluorine isotopes; fluorine-18; Gene expression; Hydrochloric acid; Kinases; Medical imaging; Pancreatic cancer; Pancreatic carcinoma; Peptide transporter; peptide transporters; Peptides; Positron emission; positron emission tomography; Radioactive tracers; Radiochemical analysis; radiotracer; Reaction time; Solid phases; Solvents; Tomography; Tumor cell lines; Tumors
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25030643

We have developed a novel fluorine-18 radiotracer, dipeptide , radiolabeled in two steps from mesylate . The initial radiolabeling is achieved in a short reaction time (10 min) and purified through solid-phase extraction (SPE) with modest radiochemical yields (rcy = 10 ± 2%, = 5) in excellent radiochemical purity (rcp > 99%, = 5). The de-protection of the -butyloxycarbonyl (Boc) and trityl group was achieved with mild heating under acidic conditions to provide F-tagged dipeptide . Preliminary analysis of F-dipeptide was performed to confirm uptake by peptide transporters (PepTs) in human pancreatic carcinoma cell lines Panc1, BxPC3, and ASpc1, which are reported to express the peptide transporter 1 (PepT1) . Furthermore, we confirmed in vivo uptake of F-dipeptide tracer using microPET/CT in mice harboring subcutaneous flank Panc1, BxPC3, and Aspc1 tumors. In conclusion, we have established the radiolabeling of dipeptide with fluoride-18, and demonstrated its potential as an imaging agent which may have clinical applications for the diagnosis of pancreatic carcinomas.