Target Specific Uptake of a Newly Synthesized Radiolabeled 5α-Reductase Inhibitor "Tc-99m-17-Oxo-17a-Aza-D-Homo-5-Androsten-3β-yl Phenoxyacetate (Tc-99m-17a-Aza Steroid)" in Rat Prostatic Neoplastic Lesions.

Autor: Jan G; Centre for Nuclear Medicine (UIEAST), Panjab University Chandigarh, India., Bhat S; Centre for Nuclear Medicine (UIEAST), Panjab University Chandigarh, India., Chauhan M; University Institute of Pharmaceutical Sciences, Panjab University Chandigarh, India., Dhawan DK; Department of Biophysics, Panjab University Chandigarh, Chandigarh, India., Dhingra N; University Institute of Pharmaceutical Sciences, Panjab University Chandigarh, India., Chadha VD; Centre for Nuclear Medicine (UIEAST), Panjab University Chandigarh, India.
Jazyk: angličtina
Zdroj: Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India [Indian J Nucl Med] 2022 Apr-Jun; Vol. 37 (2), pp. 133-141. Date of Electronic Publication: 2022 Jul 08.
DOI: 10.4103/ijnm.ijnm_128_21
Abstrakt: Objective: 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.
Materials and Methods: 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.
Results: The in-silico 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 P 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.
Conclusion: The study concludes that Tc-99m-17a-aza exhibits prostate specificity and can be explored further for its potential as a radionuclide imaging probe.
(Copyright: © 2022 Indian Journal of Nuclear Medicine.)
Databáze: MEDLINE
Externí odkaz: