Cancer Imaging and Therapy Analysis Platform (CITAP) Summary We will create a preclinical, quantitative, Cancer Imaging and Therapy Analysis Platform (CITAP, pronounced sea-tap) which will allow one to study cancer biology and optimize pipelines of technologies (imaging agents, imaging methods, targeted nano-therapeutics, immunotherapy, tumor models, etc.), especially for metastatic and invasive cancers. Today, primary tumor masses are clinically controlled with surgical, drug, and radiation therapies, but the ability to control metastatic cancer is limited and patients most often die from metastases. Arguably, metastatic cancer is the most important front in the war on cancer, but it is hampered by an inability to see the enemy. Preclinical research on micro-metastases (1 cell to 1 mm) and larger, scattered throughout the body is challenging because histology is impractical and because traditional in vivo imaging has insufficient resolution and contrast for reliable detection. CITAP will provide unique, quantitative assessments for optimiza- tion of technologies targeting metastatic and invasive cancers. The central technology will be cryo-imaging, a section-and-image technique which provides anatomical color and molecular fluorescence, single cell sensitivity, 3D microscopic imaging over vast volumes, as large as an entire mouse. This will be linked via registration software to small animal medical imaging modalities (PET, MRI, SPECT, fluorescence, ultrasound, etc.) and to histology. The platform will include experimental methods, small animal imaging, cryo-imaging, histology, and software “glue.” With visualization software, a researcher will zoom to a small GFP-labeled tumor, determine the presence of imaging agent using highly sensitive cryo-fluorescence, determine if there is detectable MR signal, and optionally examine histology for target molecules. Software will also provide unique quantitative analyses of tumor burden, including micro-metastases, heterogeneous tumor, and dispersing tumor cells, providing unique assessments of therapeutics. CITAP will add significant value to BioInVision’s product line by providing a quan- titative platform for assessments and optimization of cancer technologies.

Project Narrative: Although a primary tumor mass can be controlled, the ability to control metastatic cancer is limited and patients most often die from metastases. We will create a unique, preclinical, quantitative Cancer Imaging and Therapy Analysis Platform (CITAP) suitable for the evaluation and optimization of pipelines of technologies (imaging agents, imaging methods, therapeutics, tumor models, etc.) important for detecting, understanding, and treating metastatic and invasive cancers.