Eur J Nucl Med (1986) 12:120-124 European Nuclear Journal of Medicine © Springer-Verlag 1986 Effect of glucose and insulin infusion on the myocardial extraction of a radioiodinated methyl-substituted fatty acid* J.A. Bianco 1, D.R. Elmaleh, J.A. Leppo, M.A. King, A. Moring, E. Livni, E. Espinoza, J.S. Alpert, and H.W. Strauss Departments of 1Nuclear Medicine and Surgery and the Division of Cardiovascular Medicine, University of Massachusetts Medical Center, Worcester Massachusetts, USA Nuclear Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA Abstract. We investigated the one-way. AV extraction of 14-iodophenyl-tetradecanoic acid (BMTDA) in the canine heart under fasting conditions and during infusion of glu- cose plus insulin in eight anesthetized greyhound dogs. Myocardial extraction measurements were made with dual tracer approach, using Tc-99m albumin as reference tracer. Prior to, and during, infusion of 10% glucose and 25 units of regular insulin, heart rate, blood pressure, plasma glu- cose, insulin and free fatty acid levels were measured. Myo- cardial blood flow was determined using Sn-113 and Ru- 103 radioactive microspheres. The mean extraction fraction of BMTDA was 0.38 -t- SEM 0.06 at baseline and increased to 0.44_+ 0.06 during hyperglycemia plus insulin (P < 0.025). Plasma glucose and insulin were higher during the infusion (P<0.01) while plasma free fatty acids significantly de- clined (P< 0.01). There were no changes in hemodynamics or myocardial blood flow during the infusion. We conclude that glucose and insulin infusion result in increased first- pass extraction fraction of radioiodinated BMTDA unac- companied by changes in coronary flow or hemodynamics, implying an insulin-mediated augmented transport of BMTDA. Key words: Glucose and insulin infusion - Myocardialex- traction - Radioiodinated methyl-substituted fatty acid Radiolabeled fatty acids have been proposed as probes of cardiac metabolic integrity. Ideally, a radiolabeled fatty acid must be efficiently taken up by the myocardium in proportion to the regional utilization of the unlabeled sub- strate; after myocardial accumulation it should have mini- mal loss of the iodine label. These properties will permit a high-resolution nuclear image to be recorded, where the regional distribution of tracer is proportional to fatty acid uptake. Emission tomographic studies require a relatively stable concentration of the radioiodinated fatty acid in the myo- cardium during the 20-40 min needed to record a typical * Presented in part at the 57th Scientific Sessions, American Heart Association, 12-15 November 1984, Miami, Florida, USA; sup- ported in part from a grant from the JP Healey Endowment and the Division of Cardiovascular Medicine (UMMC) Offprint requests to: JA Bianco, M.D., Department of Nuclear Medicine, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA single-photon tomographic study. If the radiolabel is lost from the myocardium during the tomographic data acquisi- tion, the apparent regional distribution of the tracer in the reconstructed data will be incorrect. Radiolabeled fatty acids with a long myocardial resi- dence time have been reported by several investigators. Four approaches have been suggested to increase the resi- dence time of radiolabeled fatty acids in the myocardium: (1) placement of the radiolabel near the omega portion of the molecule; (2) placement of the radiolabel on a phenyl group to minimize the opportunity for diffusion of the me- tabolized fragment; (3)addition of a tellurium heteratom to the molecule to prevent beta-oxidation (Bianco et al. 1984; Elmaleh et al. 1981; Goodman et al. 1982; Okada et al. 1982); (4) addition of a methyl group to an odd- numbered carbon to preclude beta-oxidation. The speed of beta-oxidation results in rapid loss of the radiolabel from the omega-carbon. The addition of the phenyl group on the omega-position results in increase in residence time, but is still insufficient to permit recording of high-quality tomographic images. Placement of the tellurium heteroa- tom in the molecule results in marked prolongation of resi- dence time, but also made the fatty acid toxic. Radiolabeled 3-methyl (fl-methyl) heptadecanoic acid is retained in the myocardium over a l-h study period (<10% loss/hour) (CH2) 11 CH (CH3)CH 2 COOH I Fig. 1. Structural formula of 14-(p-iodophenyl) beta methyltetrade- canoic acid