DIFFERENCES IN RATES OF INCORPORATION OF INTRAVENOUSLY INJECTED RADIOLABELED FATTY-ACIDS INTO PHOSPHOLIPIDS OF INTRACEREBRALLY IMPLANTED TUMOR AND BRAIN IN AWAKE RATS

This study investigates the incorporation of three intravenously admin istered radiolabeled fatty acids, [9,10-H-3]palmitate (H-3-PAM), [1-C- 14]arachidonate (C-14-ACH) and [1-C-14]docosahexaenoate (C-14-DHA), in to lipids of intracerebrally implanted tumor and contralateral brain c ortex in awake rats. A suspension of Walker 256 carcinosarcoma cells ( 1 x 10(6) cells) was implanted into the right cerebral hemisphere of a n 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat wa s infused intravenously for 5 min with 3H-PAM (6.4 mCi/kg), C-14-ACH ( 170 mu Ci/kg) or C-14-DHA (100 mu Ci/kg). Twenty min after the start o f infusion, the rat was killed and intracranial tumor mass and brain c ortex were removed for lipids analysis. Each radiolabel was incorporat ed more into tumor than into brain cortex. Ratios of net incorporation rate coefficients (k) into tumor as compared with brain were 4.5, 3. 4 and 1.7 for H-3-PAM, C-14-ACH and C-14-DHA, respectively. Lipid radi oactivity comprised more than 80% of total tumor or brain radioactivit y for each probe. Phospholipids contained 58%, 89% and 68% of tumor li pid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for H-3-PAM, C-14-ACH and C-14-DHA, respectively. Incorporation coeffi cients (k(i)) for a phospholipid class (i)-choline phosphoglycerides (PC), inositol monophosphoglycerides (PI), ethanolamine phosphoglyceri des (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)-were g reater in tumor than in brain for each fatty acid probe, except that v alues for k(PE) and k*(PS) using C-14-DHA were equivalent. Difference s in k(i) between tumor and brain were largest for SM and PC and the change in k(PC) accounted for 65-90% of the increase in the net phosp holipid incorporation rate for each probe. Differences in k(PI), k*(P E) and k(PS) were smaller than those in k*(PC) and k*(SM), and varied with the probe. Differences in k(i) were related to differences in t umor and brain phospholipid composition and metabolism. The results in dicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumor in viv o using positron emission tomography.