脑部渗透 PARP 靶向 PET 成像探针-猫眼课题宝

脑部渗透 PARP 靶向 PET 成像探针

批准号：

10287654

负责人：

Zhengxin Cai

金额：

$8.28万

依托单位：

YALE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2020

资助国家：

美国

项目状态：

已结题

起止时间：

2020-04-01 至 2022-09-30

来源：

https://reporter.nih.gov/project-details/10287654

关键词：

APP-PS1 Administrative Supplement Affinity Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease patient Anatomy Animal Disease Models Animals Binding Blood - brain barrier anatomy Brain Brain Neoplasms Cancer Patient Cerebellum Chemotherapy and/or radiation Clinic Clinical Trials DNA Repair Data Development Drug Kinetics Funding Future Genetic Glioblastoma Glioma Grant Hippocampus (Brain)Human Hydrogen Bonding Image In Vitro Kinetics Lead Malignant Neoplasms Mediating Metabolism Modeling Molecular Weight Mus Penetration Plasma Poly(ADP-ribose) Polymerases Positron-Emission Tomography Precision therapeutics Prediction of Response to Therapy Prognosis Property Radiation therapy Rattus Rodent Model Series Specificity Spleen Synapses Testing Tracer Transgenic Organisms Translating United States National Institutes of Health base blood-brain barrier penetration blood-brain barrier permeabilization brain tissue cancer survival clinical imaging familial Alzheimer disease frontal lobe imaging agent imaging modality imaging probe imaging study improved in vivo inhibitor/antagonist kinetic model mouse model neoplastic cell neuroimaging nonhuman primate novel parent grant patient stratification pharmacokinetic model prognostic public health relevance radiotracer response translational study tumor uptake white matter

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ABSTRACT of the funded parent grant Because tumor cells can survive chemo/radiation therapies through DNA repairment mediated by poly(ADP- ribose) polymerase-1 (PARP-1). PARP-1 inhibitors (PARPis) alone, or in combination with chemotherapy or radiation therapy, have led to substantial gains in the overall survival of cancer patients, by obstructing PARP- catalyzed single DNA repair. With multiple ongoing clinical trials using PARPis to treat glioma, to quantify baseline PARP expression levels through quantitative PARP PET imaging will provide prognostic information to guide future precision treatment. However, none of the current PARP imaging agents under development is brain penetrant, making reliable in vivo quantification of PARP-1 in the brain challenging. Herein, we propose to evaluate several BBB penetrant PARP-1 inhibitors as potential PET imaging agents.

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