This S10 Shared Instrument proposal seeks funds for the purchase of a PerkinElmer Quantum GX2 small-animal X-ray computed tomography (?CT) imager to be administered by the UCSF Preclinical Therapeutics Core (PCT) and located within the Helen Diller Family Comprehensive Cancer Center (HDFCCC) Research Building vivarium on the Mission Bay campus of UCSF. The PCT has a record of successful oversight of five other high-end preclinical imaging devices across three UCSF campuses (three IVIS bioluminescence/fluorescence imagers) and two Vevo ultrasound imagers, as well as an additional XStrahl precision irradiation device. The Quantum GX2 we propose to acquire is a state-of-the-art ?CT imager that allows rapid and sensitive 3D detection of tumors and surrounding tissue in live animals (mice and rats) to inform preclinical oncology research. This instrument will support six major users and five minor users undertaking high- impact NIH-funded research projects in preclinical oncology. NIH-funded investigators will use 76% of the accessible user time (AUT) of the instrument. More specifically, NIH-funded projects of the Major Users will utilize 58% of AUT. The need for an instrument like this is high since there are few, if any, other effective molecular imaging modalities for several important classes of rodent tumor models in our institution, that include patient- derived samples, genetically-induced and carcinogen?induced models. The instrument will be particularly important in visualizing tumors located in lung, brain abdomen and bone. Historical challenges to longitudinal preclinical ?CT imaging include the fact that, due to long imaging times, throughput can be low, and that the act of delivering the X-ray energy required to detect animal tumors at adequate resolution can itself have unintended anti-tumor activity such as radiation damage and anti-proliferative effects of the radiation. The Quantum GX2 benefits from recent, improved technology that enables low radiation dose and fast scan times to provide sensitive, serial imaging in the preclinical arena. In addition, its computational algorithms allow rapid 3D image reconstruction processing to enable high scanner throughput, up to 15 subjects per hour. Finally, locating the instrument within the HDFCCC pathogen-free barrier facility greatly facilitates long-term imaging studies. There is currently no comparable high-throughput, behind-the-barrier ?CT available to UCSF investigators, and preclinical ?CT imaging studies have required transferring mice to an outside the barrier location at the UCSF China Basin Campus (Dept of Radiology and Biomedical Imaging), or sacrificing animals for ex vivo analysis on a laboratory ?CT scanner, such as in the UCSF QB3 facility. This proposal seeks NIH funds for what we deem to be the optimal solution to address these deficiencies, and support the translational research of at least eleven cutting edge research laboratories.
Rodent-based human tumor models are a valuable tool in the war on cancer. Recent preclinical methodologies enable molecularly and anatomically accurate oncology models with predictive value for evaluation of experimental anti-cancer therapeutics, but some of these tumors are difficult to detect. Dedicated small animal computed tomography (micro-CT) imaging devices such as the one we seek to acquire enable rapid, sensitive, non- invasive serial detection of tumor size, location, and response to treatment.
