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(−)‐6′,7′‐[ 11 C]Dihydroroten‐12α‐ol ((−)‐[ 11 C]DHROL) for in vivo measurement of mitochondrial Complex I
Author(s) -
Snyder Scott E.,
Sherman Phillip S.,
Desmond Timothy J.,
Frey Kirk A.,
Kilbourn Michael R.
Publication year - 1999
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199907)42:7<641::aid-jlcr226>3.0.co;2-y
Subject(s) - chemistry , in vivo , radioligand , radiosynthesis , quinolinic acid , stereochemistry , desmethyl , radiochemistry , biochemistry , in vitro , metabolite , tryptophan , amino acid , microbiology and biotechnology , biology
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.