First Human Trial of Src/Abl-Targeted PET Tumor Imaging with F-18 SKI-249380

描述（由申请人提供）：Src/Abl肿瘤激酶抑制在标准治疗失败后对常见实体类型的癌症具有临床证明的疗效，使一亚组患者受益-全球可能有数百万人。随着一波新的Src/Abl治疗方法的开发，肿瘤学家迫切需要新的Src/Abl靶向检测方法来告诉他们哪些患者将受益；指导给药策略；并帮助他们在分子水平上了解肿瘤对Src/Abl治疗的反应。如果没有找到合适的检测方法，Src/Abl实体瘤治疗可能会因总体缓解率低而被放弃，并且数百万可能对Src/Abl靶向治疗有反应的进展性实体癌患者的益处将会丧失。研究人员提出了一种新的Src/Abl诊断方法：一种非侵入性扫描，可以评估Src/Abl靶向小分子对患者体内肿瘤的靶向程度。研究人员预测，通过医学成像检测Src/Abl肿瘤靶向，将预测哪些患者将受益于Src/Abl靶向治疗，并为规划如何处方Src/Abl治疗提供新的见解。研究人员开发了18F-SKI-249380，这是首款达沙替尼示踪剂，作为正电子发射断层扫描（PET）的Src/ abl靶向显像剂。研究者需要了解Src/ abl靶向示踪剂在人体中的行为，以及它提供的辐射剂量，这是合理设计18F-SKI-249380 PET临床试验成功的先决条件。解决方案：首次在人体中进行试点试验，使用微量示踪剂18F-SKI-249380，患者毒性风险最小，PET成像和血液分析，以获得首次在人体中进行的剂量学，代谢，生物分布和排泄数据。所寻求的资金包括计划中的首次人体试验的直接费用。研究人员是一个积极进取的团队，具有成功临床开发达沙替尼示踪PET成像的杰出资格：18F-SKI-249380的发明者；她是纪念斯隆凯特琳癌症中心（MSKCC） PET/核医学服务部、放射化学-回旋加速器核心、医学物理系和肿瘤学服务部经验丰富的主治人员，包括MSKCC使用达沙替尼和其他Src/Abl治疗的实体瘤试验的主要和共同研究者。该团队的集体经验和长期合作为肿瘤成像的新型PET示踪剂的转化开发提供了成功的记录。

DESCRIPTION (provided by applicant): Src/Abl tumor kinase inhibition has clinically-proven efficacy against common solid types of cancer after standard therapy has failed, benefitting a subgroup of patients - potentially millions of people worldwide. With a wave of new Src/Abl therapeutics in development, oncologists urgently need new Src/Abl -targeted assays that can tell them which patients will benefit; guide dosing strategy; and help them understand tumor response to Src/Abl therapy at the molecular level. If no suitable assays are found, Src/Abl solid tumor therapy may be abandoned for low overall response-rates, and the benefits to potentially millions of patients with progressive solid cancer who would have responded to Src/Abl -targeted therapy will be lost. The Investigators propose a new approach to Src/Abl diagnostics: a non-invasive scan that can evaluate how well a Src/Abl-targeted small molecule targets tumors inside patients. The Investigators predict that detection of Src/Abl tumor-targeting, through medical imaging, will predict which patients will benefit from Src/Abl-targeted therapy and provide new insights for planning how to prescribe Src/Abl-therapy. The Investigators have developed 18F-SKI-249380, a first-of-its-kind dasatinib-tracer, as a Src/Abl-targeted imaging agent for positron emission tomography (PET) scanning. The Investigators need to learn how the Src/Abl-targeted tracer behaves in humans, and the radiation dose it delivers, as a prerequisite to rational design of successful clinical trials with 18F-SKI-249380 PET. Solution: A first-in-human pilot trial, using microgram tracer-dose of 18F-SKI-249380, with minimal risk of patient toxicity, PET imaging and blood assays to obtain first-in-human data on dosimetry, metabolism, biodistribution, and excretion. The funding sought covers direct costs of the planned first in-human trial. The Investigators are a motivated team with distinguished qualifications for successful clinical development of dasatinib-tracer PET imaging: the inventor of 18F-SKI-249380; experienced attending staff in the Memorial Sloan Kettering Cancer Center (MSKCC) PET/Nuclear Medicine Service, Radiochemistry- Cyclotron Core, Medical Physics Department, and Oncology Services, including principal & co-investigators of MSKCC solid tumor trials with dasatinib and other Src/Abl therapeutics. The team's collective experience and longstanding collaborations offer a track-record of success in translational development of new PET tracers for oncologic imaging.