TY - JOUR
T1 - 7α- and 17α-substituted estrogens containing tridentate tricarbonyl rhenium/technetium complexes
T2 - Synthesis of estrogen receptor imaging agents and evaluation using microPET with technetium-94m
AU - Luyt, Leonard G.
AU - Bigott, Heather M.
AU - Welch, Michael J.
AU - Katzenellenbogen, John A.
N1 - Funding Information:
We are grateful for support of this research through grants from the National Institute of Health [PHS 5R37 CA25836 (to J.A.K.) and PHS 5P01HL13851 (to M.J.W.)] and the Department of Energy [DE FG02 86ER60401 (to J.A.K.) and DE FG02 84ER60218 (to M.J.W.)]. Technetium-94m was provided by Washington University Medical School and partially funded through an NCI grant R24 CA86307. MicroPET imaging was supported by an NIH/NCI SAIRP grant (1 R24 CA83060). We would also like to thank the Small Animal Imaging Core of the Alvin J. Siteman Cancer Center at Washington University and Barnes-Jewish Hospital in St. Louis, MO, USA for additional support of the microPET imaging. The Core is supported by an NCI Cancer Center Support Grant # 1 P30 CA91842. NMR spectra were obtained in the Varian Oxford Instrument Center for Excellence in NMR Laboratory. Funding for this instrumentation was provided in part from the W. M. Keck Foundation, the National Institutes of Health (PHS 1 S10 RR104444-01), and the National Science Foundation (NSF CHE 96-10502). Mass spectra were obtained on instruments supported by grants from the National Institute of General Medical Sciences (GM 27029), the National Institutes of Health (RR 01575), and the National Science Foundation (PCM 8121494). We also thank Kathryn Carlson for the binding affinity measurements.
PY - 2003/11/17
Y1 - 2003/11/17
N2 - To develop technetium and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors, we have prepared tridentate metal tricarbonyl chelates substituted at the 7α- and 17α-positions of estradiol. Some of the Re(CO)3 conjugates have high binding for the ER in vitro. The in vivo biodistribution of the highest affinity of these novel metal tricarbonyl conjugates, prepared as the 94mTc labeled analogue, was evaluated by tissue dissection and microPET imaging. Although target tissue-selective uptake was not apparent, it is notable that microPET imaging identified the stomach as a major site of activity deposition, a site that might have been missed by standard tissue distribution studies.
AB - To develop technetium and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors, we have prepared tridentate metal tricarbonyl chelates substituted at the 7α- and 17α-positions of estradiol. Some of the Re(CO)3 conjugates have high binding for the ER in vitro. The in vivo biodistribution of the highest affinity of these novel metal tricarbonyl conjugates, prepared as the 94mTc labeled analogue, was evaluated by tissue dissection and microPET imaging. Although target tissue-selective uptake was not apparent, it is notable that microPET imaging identified the stomach as a major site of activity deposition, a site that might have been missed by standard tissue distribution studies.
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U2 - 10.1016/j.bmc.2003.09.004
DO - 10.1016/j.bmc.2003.09.004
M3 - Article
C2 - 14604660
AN - SCOPUS:0242266521
SN - 0968-0896
VL - 11
SP - 4977
EP - 4989
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 23
ER -