Targeting 5α-reductase with 99mTc labeled dutasteride derivatives for prostate imaging

Abstract To assess the suitability of 99mTc labeled 5α-reductase (5α-Rds) inhibitors for non-invasive targeting of prostate cancer (PCa) using Male Sprague Dawely Rat (MSDR) model. In this work, dutasteride (Cpd-1) a 5α-Rds inhibitor was derivatized to its dithiocarbamate analogue (Cpd-2) for subsequent synthesis of 99mTc(CO)3-dutasteride dithiocarbamate (Cpd-3) using tricarbonyl technique. To determine the structure of Cpd-3, for the first time a reference Re(CO)3-dutasteride dithiocarbamate (Cpd-4) was synthesized and characterized with NMR, ESIMS, HPLC and elemental analysis. HPLC was used to establish the identity of Cpd-3 using Cpd-4 as a reference standard. The suitability of Cpd-3 as a new 5α-Rds targeting agent was investigated, both in vitro and vivo. The Cpd-3 has shown ≥98 % in vitro stability at room temperature and was remained ≥90 % stable up to 6 h. In serum Cpd-3 has revealed an analogous behavior with a small decrease in stability after 16 h. High uptake (26.25 ± 1.10 %, after 4 h of i.v.) of Cpd-3 was observed in the prostate (target tissue) of MSDR model with reasonably good target to non-target ratio. Blocking the target site with excess Cpd-2 considerably decreased the uptake of Cpd-3 to 4.10 ± 0.75 % in PCa. High in vitro stability in saline and serum and in vivo uptake in prostate of MSDR model plausibly attracts the opportunity of using Cpd-3 as a novel radiopharmaceutical for non invasive targeting of prostate.