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Catabolism and Protein Binding of Tc-99m Pyridoxylideneglutamate

Sacramento Medical Center of the University of California at Davis School of Medicine, Sacramento, California

Correspondence: For reprints contact: Anne-Line Jansholt, Dept. of Nuclear Medicine, Sacramento Medical Center—UCD, 4301 X St., Sacramento, CA 95817.

ABSTRACT

Various Tc-99m-labeled compounds have been suggested as replacements for [I-131] rose bengal for imaging of the hepatobiliary system. Among such compounds are Schiff's bases, which are tin-free Tc-chelates easily prepared by 30-min autoclaving of an equimolar mixture of pyridoxal and an amino acid at pH 8.5. We have compared the properties of several Schiff's bases, including Tc-99m pyridoxylideneglutamate (Tc-PyG) with [I-131] rose bengal. Under conditions described, Tc-PyG can be prepared free of Tc-pyridoxal and with <2% TcO₄^– radiochemical impurity. Blood clearance and biliary excretion were studied in three animal models and in normal human volunteers. In all animal models, Tc-PyG initially cleared from the blood more rapidly than rose bengal, but a significant amount of Tc-PyG was excreted in the urine, this in contrast to [I-131] rose bengal which was almost completely excreted through the biliary system. Species differences were observed in the degree of urinary versus biliary clearance of Tc-PyG, with significantly greater urinary excretion in dogs than in monkeys and rabbits. Replacing glutamate with other amino acids did not significantly increase the blood clearance rate or decrease urinary excretion, so that Tc-PyG appears to be at least as good as any of the others studied. Tc-PyG was only 20% bound to plasma proteins, and electrophoretic and chromatographic studies did not reveal any in vivo changes of Tc-PyG before excretion in urine or bile.

FOOTNOTES

^* Picker Scholar, James Picker Foundation.