Development of Tc-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 affinity (IC) of 450.90 nM for PARP-1. The ligand NPBHYNIC was labeled with technetium-99m and six different coligands to yield [Tc]Tc-(/tricine)-NPBHYNIC ( = TPPTS, TPPMS, PSA, PDA, NIC and ISONIC). These complexes were hydrophilic and exhibited good stability , and low levels of these complexes were taken up by nontarget organs and tissues in Kunming mice. Among these complexes, [Tc]Tc-(TPPTS/tricine)-NPBHYNIC and [Tc]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 [Tc]Tc-(TPPTS/tricine)-NPBHYNIC (1.02 ± 0.07% ID/g) was greater than that of [Tc]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 [Tc]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.