Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate

Abstract

This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C-AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5-2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C-AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division.

The eicosanoid cascade: possible role in gliomas and meningiomas

“…38 39 Furthermore, Nariai et al demonstrated in a rat tumour model using Walker 256 carcinosarcoma cells that nutritionally relevant fatty acids, including AA, were more readily incorporated into brain tumour tissue than normal brain when administered intravenously. 40 Epidemiological studies on dietary fat intake and the risk of brain tumours are sparse and not consistent. 2 Giles et al reported an increased risk of glioma in adult Australians with a high intake of oils, margarine, and salad dressing.…”

Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA2β (VIA)-deficient mice

“…Within minutes after [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]DHA infusion, 80% of brain radioactivity is found as unchanged tracer in the sn -2 position of phospholipid and 10% is in triacylglycerol, with only about 10% consisting of aqueous radioactive metabolites ( 7,10,25,26 ). J in approximates the regional rate of brain DHA consumption, because unesterifi ed but not esterifi ed long-chain fatty acids enter the brain from plasma (27)(28)(29), and DHA, once lost by metabolism after being hydrolyzed from phospholipid, cannot be resynthesized de novo or signifi cantly elongated in brain (<0.1%) from its precursor ␣ -linolenic acid ( ␣ -LNA, 18:3n-3) ( 8,(30)(31)(32).…”

Neurochemical and behavioural impact of C18 fatty acids in male mice postweaning

“…23 Fatty acids, including arachidonic acid and DHA, injected into plasma are incorporated rapidly into the brain. 24–26 However, the fatty acid composition of the brain postweaning is considered relatively constant, not responding as readily to changes in dietary fat composition. 4,5 In this study, dietary C18 fatty acids following weaning had no significant impact on brain fatty acid composition except for the C18:3 diet, which increased the DHA, PUFA and ( n -3)/( n -6) ratios, coinciding with findings described earlier.…”