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Technetium-99m Galactosyl-Neoglycoalbumin: Preparation and Preclinical Studies

Division of Nuclear Medicine, University of California, Davis, Medical Center, Sacramento, California

Correspondence: For reprints contact: Robert C. Stadalnik, M.D., Division of Nuclear Medicine, University of California, Davis, Med. Ctr., 2315 Stockton Blvd., Room G206, Sacramento, CA 95817.

ABSTRACT

Technetium-99m galactosyl-neoglycoalbumin ([Tc]NGA), a labeled analog ligand to the hepatocyte-specific receptor, hepatic binding protein (HBP), was prepared and tested for labeling yield, stability, biodistribution, toxicity, and dosimetry. The ligand was synthesized by the covalent coupling of a carbohydrate bifunctional reagent, 2-imino-2-ethyloxymethyl-1- thiogalactose, to human serum albumin. Testing in mice and rabbits revealed the product to be nontoxic and apyrogenic. Technetium labeling yields in excess of 95%, by the electrolytic method, did not alter the molecular weight profile of the neoglycoalbumin. The NGA-bound activity remained stable for at least 4 hr. Biodistribution studies in rabbits demonstrated the liver as the single focus of tracer uptake. Dosimetry was based on kinetic studies in three baboons. Absorbed doses to liver, small Intestine, urinary bladder wall, and uterus were 0.089, 0.28, 0.56, and 0.88 rad/mCi, respectively. Total body, lens of the eye, red marrow, ovaries, and testes were less than 0.06 rad/mCi. High liver specificity imparted by receptor binding combined with high labeling yield, stability, acceptable dosimetry, and safety provide [Tc]NGA with the attributes required for routine clinical assessment of hepatocyte function.

FOOTNOTES

^* Present address: Division of Nuclear Medicine, University of Washington Hospital, Seattle, WA.

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