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

Andrei Molotkov,Paul E Harris,Akiva Mintz,Patrick Carberry,John W Castrillon,Sreevidya Santha,David K Leung

doi:10.3390/molecules25030643

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.

Highlights

The proton-coupled oligopeptide transport (POT), called the peptide transport (PTR), comprises a family of transporters which are found in animal, plant, yeast, archaea, and bothGram-negative and Gram-positive bacterial cells [1,2,3]
We propose the use of fluorine-18 nuclide to radiolabel a Gly-Sar dipeptide derivative since different kinases a variety of human advantages cancer cell lines likecarbon-11 bile duct epithelial and colon,Common prostate, fluorine-18 has inseveral important over labeled cells compounds
We demonstrate preliminary data confirming cell uptake of the radiolabeled dipeptide by several human pancreatic carcinoma cell lines and uptake of the

Summary

Introduction

The proton-coupled oligopeptide transport (POT), called the peptide transport (PTR), comprises a family of transporters which are found in animal, plant, yeast, archaea, and bothGram-negative and Gram-positive bacterial cells [1,2,3]. The POT family is comprised of four members (PepT1, PepT2, PHT1, and PHT2) [4,5] These elements are responsible for coordinating the intracellular transport of small peptides across membranes by coupling to an inwardly directed proton gradient and negative trans-membrane electrical potential. The normal tissue distribution of PepT1 is predominantly in the apical plasma membrane of enterocytes in the small intestine where it helps in the absorption of nutrients and small peptides [6,7]. It is found in renal proximal tubular cells and in bile duct epithelial cells. Immunohistochemistry, Western blotting, and gene expression studies revealed that PepT1 and PepT2 are over-expressed and regulated by Molecules 2020, 25, 643; doi:10.3390/molecules25030643 www.mdpi.com/journal/molecules

Objectives

Methods

Results

Conclusion