Evaluation of iPARP1 as an intraoperative imaging agent

2641 Objectives The DNA repair enzyme PARP1 is highly upregulated in malignant gliomas. The purpose of this study is to evaluate a fluorescent PARP1 inhibitor (iPARP1) [1] as a potential intraoperative brain tumor imaging agent. Methods Toxicity of iPARP1 was assessed in mice by hematologic and histopathologic analyses at 24h and 14d after injection of 50 μg iPARP1. To study the pharmacokinetics of iPARP1, fluorescence intensities of muscle, brain, and tumor tissues were imaged ex vivo at selected times post iv injection of iPARP1 in athymic nude mice bearing subcutaneous U87 xenografts. Blood half-life of iPARP1 was calculated by observing ear blood vessel fluorescence intensity using a Zeiss Lumar dissection microscope following iPARP1 intravenous administration. Ex vivo imaging of orthotopic U87 xenografts was performed 1h post injection (p.i.) with the IVIS spectrum fluorescence imaging system and followed by histopathologic analysis of the brain tumors. Metabolic stability studies were performed by analyzing fluorescent metabolites in the mouse blood plasma at selected times p.i. using HPLC. Results No adverse effects were observed after iPARP1 administration. iPARP1 concentration in U87 xenograft tumors at 2h p.i. (mean AU/px = 20.57, SE = 4.53) was markedly higher than muscle (mean AU/px = 2.85, SE= 1.73) or brain (mean AU/px = .01, SE = .01). iPARP1 was rapidly cleared from the blood (half-life α = .53 min, β = 11.14 min), and was sufficiently stable for in vivo imaging ( Conclusions iPARP1 is a promising fluorescent probe for intraoperative imaging of brain tumors. Research Support Acknowledgements: Supported by the Brain Tumor Center and the Imaging and Radiation Sciences Program of MSKCC.