LONG-CHAIN F-18 FATTY-ACIDS FOR THE STUDY OF REGIONAL METABOLISM IN HEART AND LIVER - ODD-EVEN EFFECTS OF METABOLISM IN MICE

Abstract

Regarding the potential usefulness of fluorine-tagged fatty acids in the study of regional metabolism in the heart and liver, the time courses of uptake and release of 9,10-[18F]fluorostearic acid, 2-[18F]fluorostearic acid, 16-[18F]fluorohexadecanoic acid, 17-[18F]fluoroheptadecanoic acid were investigated in several organs of NMRI mice. Whereas 2-[18F]fluorostearic acid shows very little uptake in the heart muscle but an increasing accumulation in the liver, the fatty acids with the F-18 label in the middle or at the end of the carbon chain exhibit uptake and elimination behavior similar to that of the analogous C-11 labeled compounds. After rapid concentration in the heart within 1 min, clearance takes place with fast and slow components. 16-[18F]fluorohexadecanoic acid and 17-[18F]fluoroheptadecanoic acid have different half-times of elimination. These differences are also reflected by the fact that nearly all the activity present in the heart can be recovered as fluoride(F-18) in the case of 17-[18F]fluoroheptadecanoic acid, whereas practically no fluoride was found among the metabolites of 16-[18F]fluorohexadecanoic acid. Similar differences were observed for the F-18 activity in bone. The results can be interpreted in terms of the odd-even rule: .beta. oxidation of even-numbered fatty acids ends up with [18F]fluoroacetic acid, whereas the odd-numbered fatty acids give rise to .beta.-[18F]fluoropropionic acid. Only in the latter case does dehalogenation take place leading to free fluoride, whereas fluoroacetic acid undergoes further reactions in the citric acid cycle.