PRISM: Precision Radiotherapy and Imaging of Small Mammals

项目总结/摘要 这项共享仪器赠款支持收购Xstrahl SARRP，一个小动物焦点 用于精确临床前X射线照射的锥形束计算机断层扫描（CBCT）X射线照射器。 SARRP最先进的成像和剂量输送能力将使整个UCSF的研究人员 从事从正常组织生物学到癌症治疗学的不同领域的研究。 对辐射照射影响的生物医学研究需要提供电离辐射的能力 以精确和保形的方式。SARRP复制了图像引导的外射束放射治疗 通常用于治疗人类癌症患者。现代临床X线放射治疗（XRT）选择性 靶向肿瘤而不影响周围的正常组织。这是通过将患者 使用CBCT定位，以多个角度输送准直X射线束。稳健实验 采用辐射的模型受益于体积剂量计算（体积剂量测定）， 可重复的动物定位系统。SARRP将这些功能集成到一个 平台该提案描述了将从收购中受益的许多研究计划。 SARRP，包括三个主要用户-Trever Bivona，MD，PhD; Jean中村，MD;和 威廉韦斯，医学博士，博士-以及多个额外的加州大学旧金山分校的研究人员谁将是主要或次要的 用户.支持的项目是多样的，包括：（1）改变神经元的分子机制 XRT后引起认知缺陷的功能;（2）XRT对唾液腺再生的影响， HNSCC模型;（3）针对胶质母细胞瘤，神经母细胞瘤， HNSCC、前列腺癌、肺癌和皮肤癌;（4）XRT后继发恶性肿瘤;（5）XRT- 诱导的转移和对XRT的抗性;（6）对XRT的治疗反应的生物标志物;（7）协同作用 之间的热超声治疗和XRT;和（8）病变的大脑区域的鸣禽参与 歌曲学习和控制，以获得对感觉运动和声乐学习相关的一般见解 to human人类speech语音acquisition获取. SARRP将饲养在实验动物研究中心内 海伦·迪勒家庭癌症研究大楼五楼的屏障设施。主要研究者 布鲁斯法德根博士将负责设备的技术监督，确保正确的 建立和运行，并与Young Ho Seo博士和Jean中村博士一起，将协助 用户培训和故障排除。SARRP的访问和使用将由NCI管理- 支持临床前治疗核心（PTC）设施，承担小动物临床前 UCSF科学家和附属机构（如加州大学伯克利分校和格莱斯顿研究所）的治疗研究 按服务收费SARRP将增加越来越多的成像和治疗选择 可通过PTC获得，PTC拥有适当的管理系统以适应此次收购。

PROJECT SUMMARY/ABSTRACT This Shared Instrumentation Grant supports the acquisition of the Xstrahl SARRP, a small-animal focal x-ray irradiator with cone-beam computed tomography (CBCT) for precision preclinical x-irradiation. State-of-the-art imaging and dose delivery capabilities of SARRP will enable investigators across UCSF to undertake research in diverse areas spanning from normal tissue biology to cancer therapeutics. Biomedical research into the effects of radiation exposure requires the ability to deliver ionizing radiation in a precise and conformal manner. The SARRP replicates image-guided external beam radiotherapy commonly employed to treat human cancer patients. Modern clinical x-ray radiotherapy (XRT) selectively targets the tumor while sparing surrounding normal tissue. This is achieved by coupling patient positioning using CBCT with delivery of collimated x-ray beams at multiple angles. Robust experimental models employing radiation benefit from volumetric dose calculations (volumetric dosimetry) and reproducible animal positioning systems. The SARRP incorporates these capabilities into a single platform. This proposal describes numerous research plans that will benefit from the acquisition of the SARRP, including from the three major users—Trever Bivona, MD, PhD; Jean Nakamura, MD; and William Weiss, MD, PhD — as well as multiple additional UCSF investigators who will be major or minor users. Projects to be supported are diverse and include: (1) molecular mechanisms altering neuronal function that cause cognitive deficits after XRT; (2) effects of XRT on salivary gland regeneration in HNSCC models; (3) various combinatorial therapies with targeted XRT for glioblastoma, neuroblastoma, HNSCC, prostate, lung, and skin cancer; (4) subsequent malignant neoplasm following XRT; (5) XRT- induced metastasis and resistance to XRT; (6) biomarkers of therapeutic response to XRT; (7) synergy between thermal ultrasound therapy and XRT; and (8) lesioning brain regions of songbird involved in song learning and control in order to gain general insights into sensorimotor and vocal learning relevant to human speech acquisition. The SARRP will be housed within the Laboratory Animal Research Center barrier facility on the fifth floor of the Helen Diller Family Cancer Research Building. Principal Investigator Bruce Faddegon, PhD will be responsible for technological oversight of the equipment, ensuring correct set up and running and, together with Young Ho Seo, PhD and Jean Nakamura, MD, will assist in training users and trouble-shooting. Access to and utilization of the SARRP will be managed by the NCI- supported Preclinical Therapeutics Core (PTC) facility, which undertakes small animal preclinical therapeutic studies for UCSF scientists and affiliates (such as UC Berkeley and the Gladstone Institutes) on a fee-for-service basis. The SARRP would add to a growing list of imaging and therapeutic options available through the PTC, which has management systems in place to accommodate this acquisition.