Development of 99mTc-Labeled Complexes with a Niraparib HYNIC Derivative for PARP-Positive Tumor Imaging.

As an enzyme that plays an important role in DNA repair, poly(ADP-ribose) polymerase-1 (PARP-1) has become a popular target for cancer therapy. Nuclear medicine molecular imaging technology, supplemented by radiolabeled PARP-1 inhibitors, can accurately determine the expression level of PARP-1 at lesion sites to help patients choose an appropriate treatment plan. In this work, niraparib was modified with a hydrazinonicotinamide (HYNIC) group to generate the ligand NPBHYNIC, which has an in vitro affinity (IC₅₀) of 450.90 nM for PARP-1. The ligand NPBHYNIC was labeled with technetium-99m and six different coligands to yield [^99mTc]Tc-(X/tricine)-NPBHYNIC (X = TPPTS, TPPMS, PSA, PDA, NIC and ISONIC). These complexes were hydrophilic and exhibited good stability in vitro, and low levels of these complexes were taken up by nontarget organs and tissues in Kunming mice. Among these complexes, [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC and [^99mTc]Tc-(NIC/tricine)-NPBHYNIC were selected for biodistribution in HeLa tumor-bearing BALB/c nude mice at 2 h post injection. The results revealed that the tumor uptake of [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC (1.02 ± 0.07% ID/g) was greater than that of [^99mTc]Tc-(NIC/tricine)-NPBHYNIC (0.36 ± 0.05% ID/g). Additionally, in biodistribution, single-photon emission computed tomography/computed tomography (SPECT/CT) and radioautography experiments, the tumor uptake of [^99mTc]Tc-(TPPTS/tricine)-NPBHYNIC was significantly reduced in the blocked group, indicating PARP-1 specificity. Therefore, it has potential for use as a niraparib-based tumor imaging agent that targets PARP-1.