Synthesis and Evaluation of a Radioiodinated Tracer with Specificity for Poly(ADP-ribose) Polymerase‑1 (PARP-1) in Vivo

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.