Radiopharmaceutical pharmacokinetics in animals: critical considerations

Since the advent of single photon emission computerized tomography (SPECT) and positron emission tomography (PET) various chemical ligands have been labeled with radionuclides and evaluated as tracer compounds in animal models to ascertain their suitability as potential radiopharmaceuticals for humans. In the absence of a defined algorithm to predict the diagnostic efficacy of a radiopharmaceutical, any new radioligand has to undergo preclinical evaluation even if it has excellent in vitro properties. Until now few studies have produced pharmacokinetic data that could be translated from animal models directly to humans. The purpose of this review is to highlight some critical aspects to consider during the development and validation phase of a new radiopharmaceutical. Interspecies differences and the absence of knowledge of physiological mechanism can become challenging drawbacks for obtaining a successful radiopharmaceutical. In this context, the influence of ABC transporters in neuroimaging, the effect of plasma protein binding and the consequence of anesthesia with reference to interspecies differences will be discussed with illustrative examples.