Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics.

Abstract

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.

• Authors: Hanit Marom, Keren Miller, Yossi Bechor-Bar, Galia Tsarfaty, Ronit Satchi-Fainaro, Michael Gozin
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 53 Issue 17 Pg. 6316-25 (Sep 09 2010) ISSN: 1520-4804 [Electronic] United States
• PMID: 20715870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Anilides
• Coordination Complexes
• Receptors, Androgen
• Gadolinium

Topics

• Androgen Antagonists (chemical synthesis, chemistry, metabolism)
• Anilides (chemical synthesis, chemistry, metabolism)
• Animals
• Coordination Complexes (chemical synthesis, chemistry, metabolism)
• Gadolinium
• Humans
• Magnetic Resonance Imaging
• Male
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Prostatic Neoplasms (diagnosis, metabolism)
• Receptors, Androgen (metabolism)
• Stereoisomerism
• Structure-Activity Relationship