Differences in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids of intracerebrally implanted tumor and brain in awake rats

Abstract

This study investigates the incorporation of three intravenously administered radiolabeled fatty acids, [9,10-³H]palmitate (³H-PAM), [1-¹⁴C]arachidonate (¹⁴C-ACH) and [1-¹⁴C]docosahexaenoate (¹⁴C-DHA), into lipids of intracerebrally implanted tumor and contralateral brain cortex in awake rats. A suspension of Walker 256 carcinosarcoma cells (1×10⁶ cells) was implanted into the right cerebral hemisphere of an 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat was infused intravenously for 5 min with³H-PAM (6.4mCi/kg),¹⁴C-ACH (170)μCi/kg or¹⁴C-DHA (100)μCi/(kg). Twenty min after the start of infusion, the rat was killed and intracranial tumor mass and brain cortex were removed for lipids analysis. Each radiolabel was incorporated 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 for³H-PAM,¹⁴C-ACH and¹⁴C-DHA, respectively. Lipid radioactivity comprised more than 80% of total tumor or brain radioactivity for each probe. Phospholipids contained 58%, 89% and 68% of tumor lipid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for³H-PAM,¹⁴C-ACH and¹⁴C-DHA, respectively. Incorporation coefficients (k _i ^* )for a phospholipid class (i)-choline phosphoglycerides (PC), inositol monophospho-glycerides (PI), ethanolamine phosphoglycerides (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)-were greater in tumor than in brain for each fatty acid probe, except that values fork _PE ^* andk _PS ^* using¹⁴C-DHA were equivalent. Differences ink _i ^* between tumor and brain were largest for SM and PC and the change ink _PC ^* accounted for 65–90% of the increase in the net phospholipid incorporation rate for each probe. Differences ink _PI ^* ,k _PE ^* andk _PS ^* were smaller than those ink _PC ^* andk _SM ^* , and varied with the probe. Differences ink _i ^* were related to differences in tumor and brain phospholipid composition and metabolism. The results indicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumorin vivo using positron emission tomography.