title: Synthesis and characterization of nonsteroidal-linked M(CO)(3)+ (M = 99mTc, Re) compounds based on the androgen receptor targeting molecule flutamide.
abstract: 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(OH(2))(3)(CO)(3)+, were prepared on the basis of the structure of Flutamide, a potent nonsteroidal antiandrogen prostate cancer drug. Novel bifunctional 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-(1-(2-(4-nitro-3-(trifluoromethyl)phenylamino)-2-oxoethyl)-1H-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-(1H-imidazol-1-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.
authors.affiliation: Department of Chemistry, Washington State University, P.O. Box 644630, Pullman, Washington 99164, and University Research Office, University of Idaho, Moscow, Idaho 83844, USA.
authors.forename: Haiyang
authors.initials: H
authors.lastname: He
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Morely
authors.forename: Elsa
authors.initials: E
authors.lastname: Silva-Lopez
authors.forename: Brienne
authors.initials: B
authors.lastname: Bottenus
authors.forename: Maribel
authors.initials: M
authors.lastname: Montajano
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Fugate
authors.forename: Brendan
authors.initials: B
authors.lastname: Twamley
authors.forename: Paul D
authors.initials: PD
authors.lastname: Benny
mesh_terms: D004355:Drug Stability; D005485:Flutamide / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006801:Humans; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D011944:Receptors, Androgen; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: C410798:AR protein, human; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011944:Receptors, Androgen; D005485:Flutamide