Advanced Cancer Imaging Applied in the Comparative Setting

Abstract

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.

Comparative Evaluation of Tumor-Infiltrating Lymphocytes in Companion Animals: Immuno-Oncology as a Relevant Translational Model for Cancer Therapy

“…The exact details about the similarities between the underlying genetic mechanisms, tumor development, behavior, and treatment are covered elsewhere and are thus not described in detail here [ 5 , 24 , 45 , 46 , 47 , 48 ]. Similarly, the utility of advanced and comparative imaging in veterinary patients in a clinical setting with PET-CT, CT, MRI, and others has also been described by others [ 49 , 50 ].…”

Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody

“…Companion canines with spontaneous tumors are attractive comparative models to humans for several reasons [ 14 , 15 ], including naturally occurring cancers, many with high recurrence and metastatic potential; strong genetic and molecular target similarities to human cancers; immune competence and native immuno-editing interactions between the tumor and host immune system; relevant tumor histologies with intratumoral and inter-individual heterogeneity; similar environmental carcinogen exposure to human cancers; and a more natural outbred population compared to inbred rodent model laboratory-derived canine populations. The inclusion of companion animals in the development and use of novel RIT agents also has advantages owing to their physical size and spatial distribution of tumors (primary and metastatic) and normal organs/tissues, which more closely mimics that in humans with cancer [ 16 ].…”

The Promise of Combining Radiation Therapy With Immunotherapy

“…81 Additionally, it is possible to administer clinical quality radiation therapy to dogs, and the spatial separation of tumors and normal tissues in canines more closely reflects that encountered in humans, compared with mice. 83…”