Authorship
Authors: A. Barker, R. A Powell, R S Bhopal, J M Rankin, E McColl, R Stacy, P H Pearson, E F S Kaner, L H Thomas, B G Vernon, H Rodgers
Journal: BMJ (1997)

The galactose analog 2-<sup>18</sup>F-fluoro-2-deoxy-d-galactose (<sup>18</sup>F-FDGal) is a suitable PET tracer for measuring hepatic galactokinase capacity in vivo, which provides estimates of hepatic metabolic function. As a result of a higher affinity of galactokinase toward galactose, the lumped constant (LC) for <sup>18</sup>F-FDGal was 0.13 in healthy subjects. The aim of the present study was to test the hypothesis of a significantly different LC for <sup>18</sup>F-FDGal in patients with parenchymal liver disease. <b>Methods:</b> Nine patients with liver cirrhosis were studied in connection with a previous study with determination of hepatic intrinsic clearance of <sup>18</sup>F-FDGal (<math xmlns="http://www.w3.org/1998/Math/MathML" id="m1" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow><mo>*</mo></msubsup><msubsup><mrow><mtext>/K</mtext></mrow><mi mathvariant="normal">m</mi><mo>*</mo></msubsup></mrow></math>). The present study determined the hepatic removal kinetics of galactose, including hepatic intrinsic clearance of galactose (<math xmlns="http://www.w3.org/1998/Math/MathML" id="m2" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math>/<math xmlns="http://www.w3.org/1998/Math/MathML" id="m3" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math>) from measurements of hepatic blood flow and arterial and liver vein blood galactose concentrations at increasing galactose infusions. LC for <sup>18</sup>F-FDGal was calculated as (<math xmlns="http://www.w3.org/1998/Math/MathML" id="m4" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow><mo>*</mo></msubsup><msubsup><mrow><mtext>/K</mtext></mrow><mi mathvariant="normal">m</mi><mo>*</mo></msubsup></mrow></math>)/(<math xmlns="http://www.w3.org/1998/Math/MathML" id="m5" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math>/<math xmlns="http://www.w3.org/1998/Math/MathML" id="m6" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math>). On a second day, a dynamic <sup>18</sup>F-FDGal PET study with simultaneous infusion of galactose (mean arterial galactose concentration, 6.1 mmol/L of blood) and blood samples from a radial artery was performed, with determination of hepatic systemic clearance of <sup>18</sup>F-FDGal (<math xmlns="http://www.w3.org/1998/Math/MathML" id="m7" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">K</mi><mrow><mo>+</mo><mtext>gal</mtext></mrow><mo>*</mo></msubsup></mrow></math>) from linear analysis of data (Gjedde–Patlak method). The maximum hepatic removal rate of galactose was estimated from <sup>18</sup>F-FDGal PET data (<math xmlns="http://www.w3.org/1998/Math/MathML" id="m8" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow><mrow><mtext>PET</mtext></mrow></msubsup></mrow></math>) using the estimated LC. <b>Results:</b> The mean hepatic <math xmlns="http://www.w3.org/1998/Math/MathML" id="m9" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math> of galactose was 1.18 mmol/min, the mean <math xmlns="http://www.w3.org/1998/Math/MathML" id="m10" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math> was 0.91 mmol/L of blood, and the mean <math xmlns="http://www.w3.org/1998/Math/MathML" id="m11" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math>/<math xmlns="http://www.w3.org/1998/Math/MathML" id="m12" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math> was 1.18 L of blood/min. When compared with values from healthy subjects, <math xmlns="http://www.w3.org/1998/Math/MathML" id="m13" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math> did not differ (<i>P</i> = 0.77), whereas both <math xmlns="http://www.w3.org/1998/Math/MathML" id="m14" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math> and <math xmlns="http://www.w3.org/1998/Math/MathML" id="m15" overflow="scroll"><mrow><msub><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow></msub></mrow></math>/<math xmlns="http://www.w3.org/1998/Math/MathML" id="m16" overflow="scroll"><mrow><msub><mrow><mi mathvariant="normal">K</mi></mrow><mi mathvariant="normal">m</mi></msub></mrow></math> were significantly lower in patients (both <i>P</i> &lt; 0.01). Mean LC for <sup>18</sup>F-FDGal was 0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects (<i>P</i> &lt; 0.0001). Mean <math xmlns="http://www.w3.org/1998/Math/MathML" id="m17" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">K</mi><mrow><mo>+</mo><mtext>gal</mtext></mrow><mo>*</mo></msubsup></mrow></math> determined from the PET study was 0.019 L of blood/min/L of liver tissue, which was not significantly different from that in healthy subjects (<i>P</i> = 0.85). Mean hepatic <math xmlns="http://www.w3.org/1998/Math/MathML" id="m18" overflow="scroll"><mrow><msubsup><mi mathvariant="normal">V</mi><mrow><mtext>max</mtext></mrow><mrow><mtext>PET</mtext></mrow></msubsup></mrow></math> was 0.57 mmol/min/L of liver tissue, which was significantly lower than the value in healthy subjects (1.41 mmol/min/L of liver tissue (<i>P</i> &lt; 0.0001)). <b>Conclusion:</b> Disease may change the LC for a PET tracer, and this study demonstrated the importance of using the correct LC.