Abstract

RJ Hicks
Centre for Molecular Imaging, the Peter MacCallum Cancer Centre and St Vincent’s Medical School, the University of Melbourne, Australia

Small animal PET is being increasingly used by academic institutions and pharmaceutical companies as a platform technology for translational research and drug development. Although lacking the sensitivity of optical imaging, the ability to extrapolate from animal to human studies makes PET a logical technique for both pre-clinical testing of new therapeutic drugs and validation of new tracers that might be relevant to the evaluation of human diseases. It also allows for more detailed evaluation of observations generated by human PET studies into animal models in order to understand their mechanisms. In this regard, there is a need for animal models that more closely recapitulate human diseases. Although xenograft models of cancer are widely used in cancer research, they have significant biological features that differ from those in human malignancy. These include, among many others, differences in neo-vascularity and the contribution of stromal tissue to lesion development. It is also known that hypoxia is very prevalent in xenografts but only present in a proportion of human tumour sites, even when it may be an important factor in the natural history and responsiveness to therapy of particular types of cancer. Accordingly, spontaneous tumours such as those that can occur in various transgenic mouse models, or orthotopic tumours that then spontaneously seed in a manner analogous to human malignancy, may be more appropriate to evaluate cancer therapeutics and new tracers than the traditional xenograft models. The ability to manipulate specific genes within key regulatory pathways also offers opportunities for understanding the mechanisms of disease genesis and therapeutic effects. Small animal PET is not only applicable to the study of cancer but also to other human diseases including neurological and cardiac disorders.



Keywords: animal PET, xenograft models, transgenic mouse, cancer