Journal of Medicinal Chemistry p. 8683 - 8693 (2015)
Update date:2022-08-11
Topics:
Zmuda, Filip
Malviya, Gaurav
Blair, Adele
Boyd, Marie
Chalmers, Anthony J.
Sutherland, Andrew
Pimlott, Sally L.
Interest in nuclear imaging of poly(ADP-ribose) polymerase-1 (PARP-1) has grown in recent years due to the ability of PARP-1 to act as a biomarker for glioblastoma and increased clinical use of PARP-1 inhibitors. This study reports the identification of a lead iodinated analog 5 of the clinical PARP-1 inhibitor olaparib as a potential single-photon emission computed tomography (SPECT) imaging agent. Compound 5 was shown to be a potent PARP-1 inhibitor in cell-free and cellular assays, and it exhibited mouse plasma stability but approximately 3-fold greater intrinsic clearance when compared to olaparib. An 123I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [123I]5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumor tissue and bind to PARP-1 with specificity. These findings support further investigations of [123I]5 as a noninvasive PARP-1 SPECT imaging agent.
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Doi:10.1002/jlcr.2580360503
(1995)Doi:10.1021/ol702003x
(2007)Doi:10.1246/bcsj.45.1236
(1972)Doi:10.1021/ja01250a054
(1943)Doi:10.1016/0022-328X(90)85170-4
(1990)Doi:10.1002/ejoc.201800872
(2018)