Stephanie Blocker

The study of animal models remains a cornerstone of preclinical cancer research. Recent advances in technology have led to the proliferation of animal imaging devices that are now integral to the study of cancer biology. Imaging is routinely used for the development and characterization of animal tumor models, measuring response to anticancer therapy, and for the detailed examination of individual molecular pathways within neoplastic tissue. The purpose of this chapter will be to provide an introduction to the most common imaging modalities used in contemporary oncologic investigation in order to help the reader determine if an imaging approach may complement their research goals.

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author.

Molecular imaging is a vital tool to non-invasively measure nanoparticle delivery to solid tumors. Despite the myriad of nanoparticles studied for cancer, successful applications of nanoparticles in humans is limited by inconsistent and ineffective delivery. Successful nanoparticle delivery in preclinical models is often attributed to enhanced permeability and retention (EPR)-a set of conditions that is heterogeneous and transient in patients. Thus, researchers are evaluating therapeutic strategies to modify nanoparticle delivery, particularly treatments which have demonstrated effects on EPR conditions. Imaging nanoparticle distribution provides a means to measure the effects of therapeutic intervention on nanoparticle delivery to solid tumors. This review focuses on the utility of imaging to measure treatment-induced changes in nanoparticle delivery to tumors and provides preclinical examples studying a broad range of therapeutic interventions.

Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing "cytostatic" hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue. We investigated degrees of hypothermia in vitro and identified a cytostatic window of 20° to 25°C. For some lines, 18 hours/day of cytostatic hypothermia was sufficient to halt division in vitro. Next, we fabricated an experimental tool to test local cytostatic hypothermia in two rodent GBM models. Hypothermia more than doubled median survival, and all rats that successfully received cytostatic hypothermia survived their study period. Unlike targeted therapeutics that are successful in preclinical models but fail in clinical trials, cytostatic hypothermia leverages fundamental physics that influences biology broadly. It is a previously unexplored approach that could provide an additional option to patients with GBM by halting tumor growth.