Synthesis of N-(6-[18F]Fluoropyridin-3-yl)glycine as a potential renal PET agent

Nucl Med Biol. 2019 Sep-Oct:76-77:21-27. doi: 10.1016/j.nucmedbio.2019.09.004. Epub 2019 Oct 20.

Abstract

Objective: Given the requirements of high sensitivity and spatial resolution, the development of new positron emission tomography (PET) agents is required for PET renography. The objective of this study was to investigate a new fluorine-18 labeled hippurate analogue of picolinamide, N-(6-[18F]Fluoropyridin-3-yl)glycine, as a new renal PET agent for evaluating renal function.

Methods: N-(6-[18F]Fluoropyridin-3-yl)glycine was prepared via a two-step reaction, including the nucleophilic substitution reaction of Br with 18F using methyl 2-(6-bromonicotinamido)acetate as a precursor followed the hydrolysis with sodium hydroxide and purification by preparative-HPLC. The in vitro and in vivo stability were determined using HPLC, and the plasma protein binding (PPB) and erythrocyte uptake of N-(6-[18F]Fluoropyridin-3-yl)glycine were determined using blood collected from healthy rats at 5 min post-injection. Biodistribution and dynamic micro-PET/CT imaging studies were conducted in healthy rats.

Results: N-(6-[18F]Fluoropyridin-3-yl)glycine was prepared within 45 min with an uncorrected radiochemical yield of 24.5 ± 6.7% (n = 6, based on [18F]F-) and a radiochemical purity of >98%. N-(6-[18F]Fluoropyridin-3-yl)glycine demonstrated good stability both in vitro and in vivo. The results of the biodistribution and dynamic micro-PET/CT imaging studies in normal rats indicated that N-(6-[18F]Fluoropyridin-3-yl)glycine was rapidly and exclusively excreted via the renal-urinary pathway.

Conclusion: N-(6-[18F]Fluoropyridin-3-yl)glycine is has been shown to be a promising renal PET agent and warrants further evaluation of renal function.

Keywords: N-(6-[(18)F]Fluoropyridin-3-yl)glycine; PET; Renal PET radiopharmaceutical; Renogram.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Blood Proteins / metabolism
  • Chemistry Techniques, Synthetic
  • Erythrocytes / metabolism
  • Female
  • Glycine / chemical synthesis*
  • Glycine / chemistry
  • Glycine / metabolism
  • Glycine / pharmacokinetics
  • Kidney / diagnostic imaging*
  • Positron-Emission Tomography*
  • Radiochemistry
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Blood Proteins
  • Glycine