Format

Send to

Choose Destination
Nucl Med Biol. 2006 Aug;33(6):705-13. Epub 2006 Jul 21.

Synthesis and biological evaluation of a nonsteroidal bromine-76-labeled androgen receptor ligand 3-[76Br]bromo-hydroxyflutamide.

Author information

1
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.

Abstract

INTRODUCTION:

Androgen receptors (ARs) are overexpressed in normal tissues and in most primary and metastatic prostate cancers. In our efforts to develop a nonsteroidal AR-specific imaging agent, we synthesized (+/-)-3-[(76)Br]bromo-hydroxyflutamide ((76)Br-), an analog of hydroxyflutamide, the active metabolite of the AR antagonist ligand flutamide.

MATERIALS AND METHODS:

(76)Br- was synthesized in three steps, starting with commercially available compounds. Labeling of (76)Br- was achieved through the nucleophilic opening of an epoxide intermediate, and a labeled compound was obtained in high specific activity and good radiochemical yield.

RESULTS AND DISCUSSION:

(+/-)-3-Bromo-hydroxyflutamide has a significantly higher affinity for ARs compared to hydroxyflutamide, its parent compound. The androgen target-tissue uptake of (76)Br- in diethylstilbestrol-treated male rats was examined; however, AR-mediated uptake was minimal due most likely to the rapid metabolic debromination of the radiolabeled ligand.

CONCLUSIONS:

This study is part of our first look at a novel class of nonsteroidal AR antagonists as positron emission tomography (PET) imaging agents, which are alternatives to steroidal AR agonist-based imaging agents. Although (76)Br- has a significant affinity for ARs, it showed limited promise as a PET imaging agent because of its poor target-tissue distribution properties.

PMID:
16934689
DOI:
10.1016/j.nucmedbio.2006.05.009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center