Automated Radiosynthesis of cis- and trans-4-[18F]Fluoro-l-proline Using [18F]Fluoride

J Org Chem. 2021 Oct 15;86(20):14054-14060. doi: 10.1021/acs.joc.1c00755. Epub 2021 Apr 29.

Abstract

The positron emission tomography imaging agents cis- and trans-4-[18F]fluoro-l-proline are used for the detection of numerous diseases such as pulmonary fibrosis and various carcinomas. These imaging agents are typically prepared by nucleophilic fluorination of 4-hydroxy-l-proline derivatives, with [18F]fluoride, followed by deprotection. Although effective radiofluorination reactions have been developed, the overall radiosynthesis process is suboptimal due to deprotection methods that are performed manually, require multiple steps, or involve harsh conditions. Here we describe the development of two synthetic routes that allow access to precursors, which undergo highly selective radiofluorination reactions and rapid deprotection, under mild acidic conditions. These methods were found to be compatible with automation, avoiding manual handling of radioactive intermediates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorides*
  • Fluorine Radioisotopes*
  • Halogenation
  • Positron-Emission Tomography
  • Proline

Substances

  • Fluorine Radioisotopes
  • Proline
  • Fluorides