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

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

Timaeus E F Morgan  1 , Leanne M Riley  2 , Adriana A S Tavares  1 , Andrew Sutherland  2
Affiliations

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

Timaeus E F Morgan et al. J Org Chem. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Selected examples of 18F-fluorinated α-amino acids.
Scheme 1
Scheme 1. Synthesis of cis-4-[18F]Fluoro-l-proline
Scheme 2
Scheme 2. Synthesis of Precursor 6 and cis-4-Fluoro-l-proline (1)
Scheme 3
Scheme 3. Synthesis of Precursor 11 and trans-4-Fluoro-l-proline (2)
Scheme 4
Scheme 4. Automated Radiosynthesis of cis-4-[18F]Fluoro-l-proline [18F]1 using Precursor 3
Figure 2
Figure 2
Radio-HPLC chromatogram of the reaction mixture (black). An overlay of the UV/vis HPLC trace of trans-4-fluoro-l-proline (2) (blue) and cis-4-fluoro-l-proline (1) (red) is also shown.
Scheme 5
Scheme 5. Automated Radiosynthesis of cis- and trans-4-[18F]Fluoro-l-proline ([18F]1 and [18F]2, respectively)
Decay-corrected RCYs are presented.
See this image and copyright information in PMC

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