Synthesis and evaluation of a radioiodinated tracer with specificity for poly(ADP-ribose) polymerase-1 (PARP-1) in vivo

Filip Zmuda, Gaurav Malviya, Adele Blair, Marie Boyd, Anthony J. Chalmers, Andrew Sutherland, Sally L. Pimlott

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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 (123)I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [(123)I]-5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumour tissue and bind to PARP-1 with specificity. These findings support further investigations of [(123)I]-5 as a non-invasive PARP-1 SPECT imaging agent.

Original languageEnglish
Pages (from-to)8683-8693
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number21
Early online date15 Oct 2015
Publication statusPublished - 12 Nov 2015



  • nuclear imaging
  • radioiodinated tracer
  • single-photon emission computed tomography

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