Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics.
Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodologies for preparation of novel androgen receptor-targeting agents in an attempt to build a versatile platform for prostate cancer imaging and treatment. The structure of these compounds comprises of a lanthanoid metal ion, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA)-based binding fragment and, connected to it by a flexible linker, bicalutamide-derived nonsteroidal antiandrogen moiety. A representative gadolinium complex 15 was evaluated as a magnetic resonance imaging (MRI) agent in C57/bl6 male mouse bearing orthotopic TRAMP C2 prostate tumor.
Marom
Hanit
H
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Miller
Keren
K
Bechor-Bar
Yossi
Y
Tsarfaty
Galia
G
Satchi-Fainaro
Ronit
R
Gozin
Michael
M
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000726:Androgen Antagonists; D000813:Anilides; D056831:Coordination Complexes; D011944:Receptors, Androgen; D005682:Gadolinium