TY - JOUR
T1 - Synthesis and characterization of nonsteroidal-linked M(CO) 3+(M = 99mTc, Re) compounds based on the androgen receptor targeting molecule flutamide
AU - He, Haiyang
AU - Morely, Jennifer E.
AU - Silva-Lopez, Elsa
AU - Bottenus, Brienne
AU - Montajano, Maribel
AU - Fugate, Glenn A.
AU - Twamley, Brendan
AU - Benny, Paul D.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=61849131588&partnerID=8YFLogxK
U2 - 10.1021/bc8003183
DO - 10.1021/bc8003183
M3 - Article
C2 - 19117492
AN - SCOPUS:61849131588
SN - 1043-1802
VL - 20
SP - 78
EP - 86
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 1
ER -