Nucl. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Med. Biol. Vol. 13, No. 5, pp. 577-581, 1986 In!. J. Radiat. Appl. Instrum. Part B Printed in Great Britain 0883-2897/86 $3.00 + 0.00 Pergamon Journals Ltd Metabolism of 2-[‘*F]Fluoro-2-Deoxyglucose in Tumor-Bearing Rats: Chromatographic and Enzymatic Studies ELSE-MAJ SUOLINNA,’ MERJA HAAPARANTA,* ROBERT PAUL,2,3 PIRKKO H;iRK6NEN,4 OLOF SOLIN’ and HANNU SIPIL.&’ ‘Department of Biochemistry and Pharmacy, Abe Akademi, Turku, *Turku Medical Cyclotron Project, Turku, jDepartment of Radiotherapy, Turku University Central Hospital, Turku, 4Department of Anatomy, Institute of Biomedicine, University of Turku and ‘Farmos Group Ltd, Research Center, Turku. Finland The activities of hexokinase and glucose-6-phosphatase, as well as the in vivo metabolic products of 2-[r8F]fluoro-2-deoxyglucose ([r8F]FDG) (45 min after an i.v. injection), were determined from several tissues of Rous sarcoma implanted rats. The HK/G-6-Pase ratio was found to be high in brain and tumor, and low in liver with intermediate values for kidney and muscle. In accordance with the measured enzyme activities about 90% of the 18Fwas found as [‘*F]FDG-6-P in brain, heart and tumor, whereas most of its was as [t8F]FDG in liver and kidney. In addition three minor metabolites, tentatively identified as nucleotide-derivatives of [t8F)FDG, were formed. Our results suggest that at least Rous sarcoma tumor effectively converts [‘sF]FDG to [“F)FDG-6-P and thus PET studies with [‘*flFDG can be applied to tumor diagnosis and to quantitative measurement of glucose utilization in tumor tissue according to the model of Sokoloff.‘9’ Introduction Neoplastic tissue often has an increased uptake of glucose as well as an increased rate of glycolysis as compared to normal tissue.(‘-3J This difference could be exploited in tumor detection by using glucose or glucose analogues labelled with positron-emitting nuclides, which can be detected externally. The glucose analogue 2-[‘*F]fluoro-2-deoxy-D-glucose ([‘8F]FDG) thus has potential for clinical use in tumor detection.(b6) Tumor glucose utilization could also be measured quantitatively with [‘sF]FDG and positron emission tomography (PET), provided that the necessary information on the FDG metabolism in tumor tissue is available and a mathematical model can be worked out for malignant tissue, as has been done for normal brain”’ and heart.@) The operational equation for using an analogue to measure glucose utilization relies on a compartmental model that assumes uptake of the analogue with the same carrier as glucose, trapping intracellularly in a phos- phorylated form with little loss due to back hydro- lysis, as has been shown for deoxyglucose.‘9) If [lBF]FDG is to be used for quantitative measurements of glucose metabolism in tumors with PET, its metab- olism in tumor tissue has to be characterized. The purpose of the present study was to analyze zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML in ui~o metabolism of FDG in normal tissues and tumor tissues, using both [“F]FDG and [‘4C]FDG. The activities of the two key enzymes that control glucose 6-phosphate (G-6-P) and 2-fluoro-2-deoxyglucose 6-phosphate (FDG-6-P) levels, hexokinase and glucose-6-phosphatase, were also determined in both normal and tumor tissues to test the assumption of effective trapping of [‘*F]FDG as [‘8F]FDG-6-P in tumor tissue. Material and Methods Sprague-Dawley rats (22&290 g) were used for both enzyme and metabolic studies. Tumors were produced by implanting Rous sarcoma of the Schmidt-Ruppin strain (lo) intramuscularly. The rats were used after 10-14 days, when the size of the tumor was about 2.5 x 2.5 cm. The rats received standard laboratory food and water ad libitum. Enzyme assays For enzyme assays the animals were killed by cervical dislocation; the tumor and organs to be assayed (see Table 1) were immediately removed and placed in liquid nitrogen. The tissues were pulverized with a laboratory ball mill (DismembratoP, B. Braun, Melsungen, F.R.G.) at -70°C. Hexokinase (HK, EC 2.7.1. I) was determined from the 100,000 g zyxwvut 517