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Validation of In Vivo Receptor Measurements Via In Vitro Radioassay: Technetium-99m-Galactosyl-Neoglycoalbumin as Prototype Model

Departments of Radiology and Internal Medicine, University of California, Davis, Medical Center, Sacramento, California

Correspondence: For reprints contact: Robert C. Stadalnik, MD, Division of Nuclear Medicine, University of California, Davis, Medical Center, 2315 Stockton Blvd., Sacramento, CA 95817.

ABSTRACT

Hepatic binding protein (HBP) is a hepatocyte-specific recaptor for serum asialoglycoproteins. The receptor also recognizes a synthetic glycoprotein that has been developed as a radiopharmaceutical, technetium-99m-galactosyl-neoglycoalbumin (^99mTc-NGA). This report describes the correlation between receptor parameters measured in vivo via kinetic modeling of ^99mTc-NGA and those measured by in vitro radioassay of biopsied liver tissue. Eleven patients with diffuse hepatic disease underwent percutaneous liver biopsy followed by a ^99mTc-NGA functional imaging study. In vivo measurements of HBP quantity R_o and forward binding rate constant k_b obtained from the kinetic analysis of ^99mTc-NGA liver and blood time-activity data were compared to total receptor quantity and the HBP-^99mTc-NGA association constant K_A as measured by Scatchard binding assay of the biopsied tissue. The correlation coefficients between in vivo and in vitro measurements were 0.73 (df=8, p=0.015) and 0.98 (df=8, p< 0.01) for R_o and k_b, respectively. The in vivo measurements of HBP biochemistry via kinetic analysis of the radiopharmaceutical time-activity data reflect the average concentration and affinity of the receptor. This study further substantiates the validity of ^99mTc-NGA as a quantitative probe for the HBP receptor.

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