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Molecular Imaging and Biology

, Volume 20, Issue 2, pp 205–212 | Cite as

An Automated Multidose Synthesis of the Potentiometric PET Probe 4-[18F]Fluorobenzyl-Triphenylphosphonium ([18F]FBnTP)

  • Christopher M. Waldmann
  • Adrian Gomez
  • Phillip Marchis
  • Sean T. Bailey
  • Milica Momcilovic
  • Anthony E. Jones
  • David B. Shackelford
  • Saman Sadeghi
Research Article
  • 305 Downloads

Abstract

Purpose

The aim of this study was the automated synthesis of the mitochondrial membrane potential sensor 4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) on a commercially available synthesizer in activity yields (AY) that allow for imaging of multiple patients.

Procedures

A three-pot, four-step synthesis was implemented on the ELIXYS FLEX/CHEM radiosynthesizer (Sofie Biosciences) and optimized for radiochemical yield (RCY), radiochemical purity (RCP) as well as chemical purity during several production runs (n = 24). The compound was purified by solid-phase extraction (SPE) with a Sep-Pak Plus Accell CM cartridge, thereby avoiding HPLC purification.

Results

Under optimized conditions, AY of 1.4–2.2 GBq of [18F]FBnTP were obtained from 9.4 to 12.0 GBq [18F]fluoride in 90–92 min (RCY = 28.6 ± 5.1 % with n = 3). Molar activities ranged from 80 to 99 GBq/μmol at the end of synthesis. RCP of final formulations was > 99 % at the end of synthesis and > 95 % after 8 h. With starting activities of 23.2–33.0 GBq, RCY decreased to 16.1 ± 0.4 % (n = 3). The main cause of the decline in RCY when high amounts of [18F]fluoride are used is radiolytic decomposition of [18F]FBnTP during SPE purification.

Conclusions

In initial attempts, the probe was synthesized with RCY < 0.6 % when starting activities up to 44.6 GBq were used. Rapid radiolysis of the intermediate 4-[18F]fluorobenzaldehyde and the final product [18F]FBnTP during purification was identified as the main cause for low yields in high-activity runs. Radiolytic decomposition was hindered by the addition of radical scavengers during synthesis, purification, and formulation, thereby improving AY and RCP. The formulated probe in injectable form was synthesized without the use of HPLC and passed all applicable quality control tests.

Key words

4-[18F]Fluorobenzyl-triphenylphosphonium [18F]FBnTP Mitochondrial metabolism Positron emission tomography 4-[18F]fluorobenzaldehyde Radiolysis Antioxidants Solid-phase extraction purification 

Notes

Acknowledgements

We would like to thank Dr. Michael E. Phelps for support and guidance with this study; Dr. Roger Slavik, Krzysztof Bobinski, and Daniel Yeh for providing [18F]fluoride; Dr. Jason Lee, Dr. Tove Olafsen, and Charles Zamilpa for their help with the small animal imaging; and Dr. Michael van Dam, Jeffrey Collins as well as Krzysztof Bobinski for valuable technical input.

Funding Information

The authors gratefully acknowledge the support from NIH through program, research, and training grants (CA186842, CA208642 and CA086306) and the support from the Department of Energy (DE-SC0012353).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2017_1119_MOESM1_ESM.pdf (188 kb)
ESM 1 (PDF 187 kb)
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ESM 2 (PDF 227 kb)
11307_2017_1119_MOESM3_ESM.pdf (206 kb)
ESM 3 (PDF 205 kb)
11307_2017_1119_MOESM4_ESM.pdf (508 kb)
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Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Christopher M. Waldmann
    • 1
  • Adrian Gomez
    • 2
  • Phillip Marchis
    • 1
  • Sean T. Bailey
    • 3
  • Milica Momcilovic
    • 3
  • Anthony E. Jones
    • 1
  • David B. Shackelford
    • 3
  • Saman Sadeghi
    • 1
  1. 1.Department of Molecular and Medical Pharmacology, David Geffen School of MedicineUniversity of California Los AngelesLos AngelesUSA
  2. 2.Department of Chemistry and BiochemistryUniversity of California Los AngelesLos AngelesUSA
  3. 3.Department of Pulmonary and Critical Care Medicine, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

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