SARRP for Multimodality Image-Guided Stereotactic Irradiation

Abstract public domain (NIH RePORTER)

ABSTRACT: The University of Michigan has numerous NIH funded research programs that have a critical need for instrumentation that permits delivery of ionizing radiation to precise anatomical regions in preclinical models using image guidance. After consultation with institutions which currently have this capability as well as commercial vendors of this instrumentation, the University of Michigan team of investigators is requesting funds to purchase the Xstrahl Small Animal Radiation Research Platform (SARRP). The SARRP system includes: a 225kV x-ray tube, x-ray controller, SARRP software interface and PC, robotic specimen stage, safety interlock system, cone beam CT (CBCT), a bioluminescence imaging system, and integrated shielding. Initially, 8 major users with NIH funding have been identified whose research would be enhanced by the SARRP. This includes Dr. Lawrence who evaluates radiation sensitizers in pancreatic ductal adenocarcinomas (PDAC) and is developing adaptive radiation therapy in liver and lung cancer, as well as Dr. Morgan who is evaluating radiosensitization by DNA damage response and E3 ubiquitin ligase inhibitors in PDAC and relevant normal tissues. Dr. Rehemtulla utilizes intracranial mouse patient-derived xenograft (PDX) models to investigate the genomic basis for resistance to temozolomide and radiation. Dr. Neamati uses intracranial glioblastoma (GBM) models to assess the efficacy of protein disulfide isomerase specific small molecules in combination with radiation therapy. Dr. Buchman is conducting studies in rodent models for optimization of bone regeneration in the irradiated mandible. Dr. Castro is evaluating therapies that enhance anti-tumor immunity in GBM using syngeneic intracranial models. Thus, a wide range of radiation biology studies, from drug-radiation interactions, immunotherapy, and normal tissue toxicity would be made more clinically relevant by the SARRP. The principal investigator and primary user, Dr. Theodore Lawrence, department chair and a practicing radiation oncologist, is recognized as a world-renowned leader in translational radiation oncology, targeted radiation sensitizers and image-guided radiation therapy. He has assembled a strong team to oversee the efficient utilization of the SARRP with scientific rigor including radiation physicists, as well as experts in stereotactic radiation delivery, imaging and cancer biology. The SARRP will be incorporated within the Experimental Irradiation Shared Resource (EISR) of the University of Michigan Comprehensive Cancer Center (UMCCC). This will ensure seamless daily operations, efficient scheduling and billing, as well as timely equipment maintenance. The Department of Radiation Oncology and the UMCCC have made a significant institutional commitment toward the purchase of the SARRP. The addition of a SARRP to the EISR at the University of Michigan will enable currently funded and future investigators to conduct radiation studies using clinically relevant orthotopic and genetically engineered mouse models wherein contributions of the tumor microenvironment to cancer progression and therapeutic response are taken into account.

Public health relevance public domain (NIH RePORTER)

Project Narrative: Image-guided conformal radiation permits delivery of the maximum dose to the tumor while sparing the dose to the normal tissues and is the standard of patient care today. The ability to deliver conformal radiation in animal models has only recently become available through the use of Small Animal Radiation Research Platforms (SARRP). We are requesting funding to acquire the SARRP instrument so that researchers at the University of Michigan can deliver image-guided conformal radiation to animal models of cancer. The availability of this instrument will enable scientists at the institution to test the efficacy of new cancer therapies that will positively impact our ability to treat and cure cancer.