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

Abstract

We have developed a novel fluorine-18 radiotracer, dipeptide 1, radiolabeled in two steps from mesylate 3. 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%, n = 5) in excellent radiochemical purity (rcp > 99%, n = 5). The de-protection of the tert-butyloxycarbonyl (Boc) and trityl group was achieved with mild heating under acidic conditions to provide 18F-tagged dipeptide 1. Preliminary analysis of 18F-dipeptide 1 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 18F-dipeptide tracer 1 using microPET/CT in mice harboring subcutaneous flank Panc1, BxPC3, and Aspc1 tumors. In conclusion, we have established the radiolabeling of dipeptide 1 with fluoride-18, and demonstrated its potential as an imaging agent which may have clinical applications for the diagnosis of pancreatic carcinomas.

Uptake Transporters of the SLC21, SLC22A, and SLC15A Families in Anticancer Therapy—Modulators of Cellular Entry or Pharmacokinetics?

“…In addition to the insufficient intratumoral accumulation, it was shown that BPAs are also substrates of amino acid transporters LAT1, LAT2, and ATB0, +, when overexpressed in Xenopus laevis oocytes, indicating that BPAs are not specific for PEPT1 [222]. Finally, two PEPT radiotracers, 11 C-glycyl-sarcosine and the more sTable 18F-glycyl-sarcosine, were tested for imaging of tumors highly expressing PEPT such as pancreatic, gastric, and prostate tumors [223,224]. In mice bearing subcutaneous AsPC-1 cell-derived tumors, Mitsuoka et al [223] found an advantageous tumor-to-blood ratio which was increased several fold over the muscle-to-tumor ratio.…”