Advanced Cancer Imaging Applied in the Comparative Setting.

The potential for companion (pet) species with spontaneously arising tumors to act as surrogates for preclinical development of advanced cancer imaging technologies has become more apparent in the last decade. The utility of the companion model specifically centers around issues related to body size (including spatial target/normal anatomic characteristics), physical size and spatial distribution of metastasis, tumor heterogeneity, the presence of an intact syngeneic immune system and a syngeneic tumor microenvironment shaped by the natural evolution of the cancer. Companion species size allows the use of similar equipment, hardware setup, software, and scan protocols which provide the opportunity for standardization and harmonization of imaging operating procedures and quality assurance across imaging protocols, imaging hardware, and the imaged species. Murine models generally do not replicate the size and spatial distribution of human metastatic cancer and these factors strongly influence image resolution and dosimetry. The following review will discuss several aspects of comparative cancer imaging in more detail while providing several illustrative examples of investigational approaches performed or currently under exploration at our institutions. Topics addressed include a discussion on interested consortia; image quality assurance and harmonization; image-based biomarker development and validation; contrast agent and radionuclide tracer development; advanced imaging to assess and predict response to cytotoxic and immunomodulatory anticancer agents; imaging of the tumor microenvironment; development of novel theranostic approaches; cell trafficking assessment via non-invasive imaging; and intraoperative imaging to inform surgical oncology decision making. Taken in totality, these comparative opportunities predict that safety, diagnostic and efficacy data generated in companion species with naturally developing and progressing cancers would better recapitulate the human cancer condition than that of artificial models in small rodent systems and ultimately accelerate the integration of novel imaging technologies into clinical practice. It is our hope that the examples presented should serve to provide those involved in cancer investigations who are unfamiliar with available comparative methodologies an understanding of the potential utility of this approach.