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Katzenellenbogen, John A. Liu, Aijun 2011-05-07T12:08:02Z 2011-05-07T12:08:02Z 10000-01-01 1991 In order to develop androgen receptor (AR) based probes for in vivo imaging of prostatic cancer using positron emission tomography (PET), four pairs of 16$\beta$- and 16$\alpha$-fluoro androgens, as well as two 20-fluoro androgens have been synthesized. The fluorination was achieved mainly by nucleophilic fluoride displacement of a triflate or a spirocyclic sulfate precursor, prepared by multistep synthesis. Of the ten fluorinated androgens, 16$\beta$-F-DHT (1), 16$\beta$- and 16$\alpha$-F-Mib (5 and 6), 16$\beta$- and 16$\alpha$-F-MNT (7 and 8), 20-F-Mib (9), as well as 20-F-R1881 (10) were found to have high relative binding affinity for AR, 19%-53% of the potent androgen R1881. In most cases, the fluorination improved the binding selectivity of the androgens to AR vs. other steroid receptors and SBP, and the 16$\beta$-fluoro androgens have higher affinity than their corresponding 16$\alpha$-fluoro epimers. Other interesting structure-activity relationships were observed. Seven of these fluorinated androgens have been prepared in fluorine-18 labeled form, and their in vivo tissue distribution have been studied in estrogen-treated mature male rats. All seven fluorine-18 labeled androgens showed selective and blockable target tissue uptake: the prostate to blood and prostate to muscle ratios (at 4 h) were from 5 (20-F-R1881) to 30 (16$\alpha$-F-MNT), and the uptake in the unblocked animals were 2.5 (16$\beta$-F-Mib) to 5.3 (16$\alpha$-F-MNT and 20-F-MIb) fold higher than that in the blocked animals. Rapid in vivo defluorination was observed with three 16$\beta$-fluoro androgens (1, 3 and 7). Thus, we have synthesized the first fluorine-18 labeled androgens that have relative high binding affinity and selectivity for AR, and show selective target tissue uptake. It appears that 16$\beta$-F-F-Mib (5), 16$\alpha$-F-MNT (8) and 20-F-Mib (9) are the most promising candidates as in vivo imaging agents for prostatic cancer. Made available in DSpace on 2011-05-07T12:08:02Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9210898.pdf: 6800363 bytes, checksum: 9b818e792adf104faf626a8fa65b4b2c (MD5) Previous issue date: 1991 Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:37:04Z Item is restricted indefinitely. Restriction data tranferred 2014-07-01T11:15:10-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission ETDs are only available to UIUC Users without author permission U of I Only AAI9210898 (UMI)AAI9210898 http://hdl.handle.net/2142/19453 eng Copyright 1991 Liu, Aijun Chemistry, Organic Chemistry, Pharmaceutical Health Sciences, Radiology Chemistry, Nuclear Synthesis and evaluation of fluorine-18 labeled androgens as in vivo imaging agents for prostatic cancer using PET text Chemistry Chemistry University of Illinois at Urbana-Champaign Dissertation Ph.D.