Jan Gowsia, Bhat Swati, Chauhan Monika, Dhawan Devinder Kumar, Dhingra Neelima, Chadha Vijayta Dani
Centre for Nuclear Medicine (UIEAST), Panjab University Chandigarh, India.
University Institute of Pharmaceutical Sciences, Panjab University Chandigarh, India.
Indian J Nucl Med. 2022 Apr-Jun;37(2):133-141. doi: 10.4103/ijnm.ijnm_128_21. Epub 2022 Jul 8.
Considering the 5α-reductase (5AR) inhibitory activity of the oximes and the importance of the ester group in increasing the anti-androgenic property, we reasoned to synthesize a compound having a lactam group in ring D and an ester group at the 3 β position of the androsterone nucleus. The study aims to radiolabel 17-oxo-17a-aza-D-homo-5-androsten-3β-yl phenoxyacetate (17a-aza steroid) with Tc-99m to evaluate its targeted uptake in experimentally induced prostate carcinogenesis in rats.
The prediction of the optimal interaction and binding affinity of Tc-99m-17-oxo-17a-aza-D-homo-5-androsten-3 β-ylphenoxyacetate (Tc-99m-17a-aza steroid) toward 5AR inhibitor was done using Biopredicta Vlife MDS tool. Tc-99m-17a-aza steroid was developed by direct radiolabeling protocol. The radio-pharmacological characteristics (serum stability, plasma protein-binding ability, and lipophilicity) of the complex were evaluated. Further, the bio-distribution studies of the complex were performed in rats with experimentally induced prostate carcinogenesis.
The analysis exhibits favorable binding of Tc-99m-17a-aza toward 5AR with D score-130.97. The radiochemical purity of Tc-99m-17a-aza was 96.79%. The radio-complex maintained stability in the rat serum for a period of 6 h (hours). Plasma protein binding and Log o/w value were observed to be 86.23 ± 7.08% and 0.118 ± 0.045, respectively. A significantly enhanced percent-specific uptake was observed in the prostate of rats with induced prostate carcinogenesis.
The study concludes that Tc-99m-17a-aza exhibits prostate specificity and can be explored further for its potential as a radionuclide imaging probe.
鉴于肟类化合物的5α-还原酶（5AR）抑制活性以及酯基在增强抗雄激素特性方面的重要性，我们推断合成一种在D环具有内酰胺基团且在雄甾酮核3β位具有酯基的化合物。本研究旨在用Tc-99m对17-氧代-17α-氮杂-D-高-5-雄烯-3β-基苯氧基乙酸酯（17α-氮杂甾体）进行放射性标记，以评估其在大鼠实验性诱导前列腺癌中的靶向摄取情况。
使用Biopredicta Vlife MDS工具预测Tc-99m-17-氧代-17α-氮杂-D-高-5-雄烯-3β-基苯氧基乙酸酯（Tc-99m-17α-氮杂甾体）与5AR抑制剂的最佳相互作用和结合亲和力。通过直接放射性标记方案制备Tc-99m-17α-氮杂甾体。评估该配合物的放射药理学特性（血清稳定性、血浆蛋白结合能力和亲脂性）。此外，在实验性诱导前列腺癌的大鼠中进行该配合物的生物分布研究。
分析显示Tc-99m-17α-氮杂与5AR具有良好的结合，D评分为-130.97。Tc-99m-17α-氮杂的放射化学纯度为96.79%。该放射性配合物在大鼠血清中保持6小时的稳定性。血浆蛋白结合率和Log o/w值分别为86.23±7.08%和0.118±0.045。在诱导前列腺癌的大鼠前列腺中观察到特异性摄取百分比显著增加。
该研究得出结论，Tc-99m-17α-氮杂具有前列腺特异性，可进一步探索其作为放射性核素成像探针的潜力。
