Applications of positron emission tomography in the development of molecular targeted cancer therapeutics.

Abstract

For molecular targeted cancer therapies to fulfill their promise in cancer treatment, innovative approaches are required to overcome significant obstacles that exist in the clinical development of these agents. Positron emission tomography (PET) is a functional imaging technology that allows rapid, repeated, noninvasive, in vivo assessment and quantification of many biological processes and in some cases molecular pathways targeted by these therapies. It is highly sensitive, with the capacity to detect subnanomolar concentrations of radiotracer and provides superior image resolution to conventional nuclear medicine imaging with gamma cameras. Novel PET radiotracers have been developed that allow visualisation of a variety of processes including tumour metabolism, cell proliferation, apoptosis, hypoxia and blood flow. Furthermore, specific molecular targets including cellular receptors can be identified using radiolabelled receptor ligands or specific monoclonal antibodies. Improvements in imaging technology leading to the development of small-animal PET scanners, with resolution capable of imaging commonly used mouse models of cancer, will enable PET to play an important role in preclinical proof-of-principle drug studies. Such improvements will also facilitate the validation of imaging protocols that can be readily translated to studies in humans. The greatest utility of PET in the development of molecular targeted therapeutics, however, lies in clinical studies, where PET may play a valuable role in a number of situations. These include selection of patients for therapy through noninvasive identification of the presence of specific molecular targets, pharmacokinetic studies with labelled drugs and pharmacodynamic evaluations of biological parameters to select the optimal biological dose, and assessment of response to therapies.