Approaches using molecular imaging technology -- use of PET in clinical microdose studies

Adv Drug Deliv Rev. 2011 Jun 19;63(7):539-46. doi: 10.1016/j.addr.2010.09.011. Epub 2010 Sep 29.

Abstract

Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and is extending its range of application to many other fields of pharmaceutical medicine. Although requirements for preclinical safety testing for microdose studies have been cut down by regulatory authorities, radiopharmaceuticals increasingly need to be produced under good manufacturing practice (GMP) conditions, which increases the costs of PET microdosing studies. Further challenges in PET microdosing include combining PET with other ultrasensitive analytical methods, such as accelerator mass spectrometry (AMS), to gain plasma PK data of drugs, beyond the short PET examination periods. Finally, conducting clinical PET studies with radiolabeled drugs both at micro- and therapeutic doses is encouraged to answer the question of dose linearity in clinical microdosing.

Publication types

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

MeSH terms

  • Animals
  • Clinical Trials, Phase I as Topic / economics
  • Clinical Trials, Phase I as Topic / legislation & jurisprudence
  • Clinical Trials, Phase I as Topic / methods*
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Drug Design*
  • Humans
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Pharmaceutical Preparations
  • Radiopharmaceuticals