Synthesis and Preclinical Evaluation of 99ᵐTc-HYNIC-Finasteride: A Novel SPECT Radiotracer Targeting 5α-Reductase in Prostate Cancer.

We describe the synthesis and preclinical assessment of a novel technetium-99m-labeled 5α-reductase (5AR) inhibitor, a 5AR-targeting drug, a target enzyme of prostate cancer (PCa) pathology, as a SPECT imaging probe. Finasteride was attached to 6-hydrazinonicotinic acid (HYNIC) with HYNIC NHS ester chemistry. The HYNIC-finasteride conjugate was identified by NMR, IR, MP analysis, high-resolution ESI MS ([M + H]+ m/z 507.3190, Δppm -3.9), and RP HPLC (Rt 13.9 min, > 98% purity). 99ᵐTc radiolabeling using tricine/EDDA co-ligands resulted in > 98% radiochemical purity. The radiotracer was highly stable in vitro (> 91% in PBS at 4 h; ≥ 68% in serum at 16 h) and had a logP value of -1.25 ± 0.08, with good hydrophilicity. Saturation binding assays in LNCaP cells had 5AR, with Kd and Bmax values of 3.10 ± 0.7 nM and 82.44 ± 3.2 fmol/106 cells. Biodistribution studies in LNCaP xenograft-bearing mice showed high tumor uptake (5.62% ± 0.32% ID/g at 4 h), which reduced in blocked groups (1.25% ± 0.18% ID/g). SPECT images offered selective tumor accumulation with good tumor-to-normal tissue contrast and renal clearance in tumor-bearing rabbits. These findings suggest that 99ᵐTc-HYNIC-finasteride is a promising SPECT radiotracer for noninvasive 5AR imaging in PCa.