(−)-6′,7′-[ 11 C]Dihydroroten-12Α-ol ((−)-[ 11 C]DHROL) for in vivo measurement of mitochondrial Complex I
dc.contributor.author | Snyder, Scott E. | en_US |
dc.contributor.author | Sherman, Phillip S. | en_US |
dc.contributor.author | Desmond, Timothy J. | en_US |
dc.contributor.author | Frey, Kirk A. | en_US |
dc.contributor.author | Kilbourn, Michael R. | en_US |
dc.date.accessioned | 2006-04-19T13:55:24Z | |
dc.date.available | 2006-04-19T13:55:24Z | |
dc.date.issued | 1999-07 | en_US |
dc.identifier.citation | Snyder, Scott E.; Sherman, Phillip S.; Desmond, Timothy J.; Frey, Kirk A.; Kilbourn, Michael R. (1999)."(−)-6′,7′-[ 11 C]Dihydroroten-12Α-ol ((−)-[ 11 C]DHROL) for in vivo measurement of mitochondrial Complex I." Journal of Labelled Compounds and Radiopharmaceuticals 42(7): 641-652. <http://hdl.handle.net/2027.42/34874> | en_US |
dc.identifier.issn | 0362-4803 | en_US |
dc.identifier.issn | 1099-1344 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34874 | |
dc.description.abstract | Deficits in Complex I (NADH-ubiquinone oxidoreductase) of the electron transport chain may play an important role in the inception and progression of neurodegenerative diseases such as Parkinson's disease. In vivo imaging of Complex I offers a unique method for evaluation of these changes in living human brain. Previous carbon-11 labeled rotenoids showed promising results, but were prepared as mixtures of stereoisomers at the 5′-position. We report here the stereospecific syntheses of (−)-6′,7′-[ 11 C]dihydroroten-12Α-ol ((−)-[ 11 C]DHROL), a modified rotenoid with in vivo affinity for Complex I. O -[ 11 C]methylation of the appropriate desmethyl precursor provided (−)-[ 11 C]DHROL in an average radiochemical yield, corrected to end of bombardment, of 27% (n=4) and >99% radiochemical purity. In mice, (−)-[ 11 C]DHROL gave a high and uniform brain uptake similar to that obtained with prior radiolabeled rotenoids. Further in vivo evaluation of (−)-[ 11 C]DHROL in rats with unilateral quinolinic acid-induced striatal lesions showed significant losses of radioligand binding after neurotoxin treatment (lesion/unlesioned ratio of 0.66). As this reduction of in vivo radioligand binding is very similar to that obtained previously with the mixture of [ 11 C]DHROL isomers, the stereochemistry at the 5′-position of [ 11 C]DHROL does not significantly influence the in vivo applications of this radiotracer. Copyright © 1999 John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 551639 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | (−)-6′,7′-[ 11 C]Dihydroroten-12Α-ol ((−)-[ 11 C]DHROL) for in vivo measurement of mitochondrial Complex I | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Radiology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 | en_US |
dc.contributor.affiliationum | Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 ; Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center B1G 412 University Hospital, Ann Arbor, MI 48109, USA. | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34874/1/226_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/(SICI)1099-1344(199907)42:7<641::AID-JLCR226>3.0.CO;2-Y | en_US |
dc.identifier.source | Journal of Labelled Compounds and Radiopharmaceuticals | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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