Synthesis and characterization of nonsteroidal-linked M(CO) ₃⁺(M = ^99mTc, Re) compounds based on the androgen receptor targeting molecule flutamide

Androgen receptors are overexpressed in most primary and metastatic prostate cancers. A series of single photon emission computed tomography imaging agents (SPECT) utilizing the organometallic radioactive imaging species, fac-^99mTc(OH₂)₃(CO)₃⁺, were prepared on the basis of the structure of Flutamide, a potent nonsteroidal antiandrogen prostate cancer drug. Novel Afunctional chelate-linked Flutamide analogues were prepared using a newly developed universal alkylating reagent, 2-bromo-N-[4-nitro-3-(trifluoromethyl)phenyl]-acetamide, 1. From compound 1, several ligands (i.e., cysteine 2, histidine 5, imidazole 3) were conjugated to the flutamide derivative to yield targeting ligands capable of either tridentate or monodentate coordination in a "2 +1" complex. fac-Re(CO) ₃⁺ complexes were prepared and characterized with the functionalized conjugates to yield fac-Re(CO)₃(2-amino-3-(l-(2-(4- nitro-3-(trifluoromethyl)phenylamino)-2-oxoethyl)-lH-imidazol-4-yl) propanoate), 4,fac-Re (CO)₃(2-(S-cysteinyl)- N-[4-nitro-3-(trifluoromethyl) phenyl]-acetamide), 6, and fac-Re(CO)₃(picolinate)(2-(lH-imidazol-l- yl)-N-[4-nitro-3-(trifluoromethyl)phenyl]-acetamide), 7. The corresponding radioactive ^99mTc analogues were prepared and stability studies of the radioactive compounds were also conducted.