Gallium-labeled deferoxamine-galactosyl-neoglycoalbumin: a radiopharmaceutical for regional measurement of hepatic receptor biochemistry.
Galactosyl-neoglycoalbumin (NGA) is a synthetic ligand to the hepatocyte-specific receptor, hepatic binding protein. In-vitro and in-vivo characterization of a chelation-based derivative of NGA, deferoxamine-galactosyl-neoglycoalbumin (DF-NGA), is described. A two-step glutaraldehyde method was used to covalently couple deferoxamine (DF) to NGA. Products with an average DF-to-NGA ratio of less than 2 contained less than 3% polymeric DF-NGA. All products retained the chelator after 12 mo of storage at 4 degrees C. Gallium labeling of DF-NGA-41 (41 galactose units per HSA) with an average of 1.1 DF per NGA was quantitative within 15 min after the addition of 67Ga-citrate. The labeled product was stable for at least 24 hr. Scatchard and reverse-binding assays of 67Ga-DF-NGA-41 revealed a forward binding rate constant kb similar to that of 125I-NGA-44. The %ID of 67Ga-DF-NGA-41 in rabbit liver was approximately 90% at 10 min after injection of 1.2 x 10(-9) mole DF-NGA per kilogram of body weight. This value decreased to 40% at a scaled molar dose of 1.2 x 10(-7) mol/kg. Biodistribution data of 67Ga-DF-NGA in rabbits was similar to 99mTc-NGA. High tissue specificity and facile labeling will make 68Ga-labeled neoglycoalbumin an ideal agent for regional measurements of receptor biochemistry in the investigational and clinical setting.
Vera
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Department of Radiology, University of California, Davis, Medical Center, Sacramento, California 95817.
D000418:Albumins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D037263:Asialoglycoprotein Receptor; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003676:Deferoxamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D011817:Rabbits; D014018:Tissue Distribution
D000418:Albumins; D037263:Asialoglycoprotein Receptor; D002352:Carrier Proteins; D005710:Gallium Radioisotopes; C064861:galactosyl-neoglycoalbumin; C027122:hepatic sialoglycoprotein receptor; D003676:Deferoxamine