Chemistry Considerations for the Clinical Translation of Oncology PET Radiopharmaceuticals

Mol Pharm. 2020 Jul 6;17(7):2245-2259. doi: 10.1021/acs.molpharmaceut.0c00328. Epub 2020 Jun 5.

Abstract

Positron emission tomography (PET) has proven to be an invaluable tool in the staging and management of disease in oncology; however, [18F]fluorodeoxyglucose ([18F]FDG) remains the most widely used PET radiopharmaceutical despite the large financial investment in novel radiotracer development. We report our perspective and experience of translating radiopharmaceuticals into clinical studies, discussing the PET development pipeline from a chemistry perspective. We hope that, by identifying potential points of attrition along the pipeline and suggesting solutions to these problems, we may help others take their preclinical radiotracers into human studies. This review focuses primarily on the development of fluorine-18 radiopharmaceuticals, although the broader field of radiometal chemistry is considered where the translation journey is similar.

Keywords: clinical translation; metabolism; positron emission tomography; radiochemistry; radiopharmaceuticals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Development / methods
  • Drug Discovery / methods
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18 / adverse effects
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Fluorodeoxyglucose F18 / therapeutic use*
  • Humans
  • Neoplasms / radiotherapy*
  • Positron-Emission Tomography / methods*
  • Radiation Oncology / methods*
  • Radiochemistry / methods
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Treatment Outcome

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Fluorine-18