Synthesis and Preclinical Evaluation of 99 ᵐTc‐HYNIC–Finasteride: A Novel SPECT Radiotracer Targeting 5α‐Reductase in Prostate Cancer
Makaleler > Tam Makale · 2025
Yazarlar: Saba Shirin, syed qaiser shah, Ralph Santos Olievera, Derya İLEM ÖZDEMİR
Journal of Labelled Compounds and Radiopharmaceuticals, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2025, cilt 68, ss e4167-e4167
DOI: 10.1002/jlcr.4167
Özet
ABSTRACT 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). 99 ᵐTc 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/10 6 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 99 ᵐTc‐HYNIC–finasteride is a promising SPECT radiotracer for noninvasive 5AR imaging in PCa.