title: In vivo biodistribution of a radiolabeled blood substitute: 99mTc-labeled liposome-encapsulated hemoglobin in an anesthetized rabbit.
abstract: Liposome-encapsulated hemoglobin (LEH) is an erythrocyte substitute that is a potential resuscitative fluid for the in vivo delivery of oxygen. We have noninvasively imaged radiolabeled LEH in vivo with technetium-99m (99mTc) to study the biodistribution in an anesthetized rabbit. Rabbits (2.5 kg, n = 8) were infused with 30 ml of LEH (200 mg of phospholipid, 2.5 g of hemoglobin per kg of body weight) and imaged with a gamma camera continuously for 2 hr. At 20 hr postinfusion, the animals were imaged again and sacrificed; the organs were weighted and their radioactivity was determined for autopsy organ distribution. Organ uptake from the images was corrected for organ-associated blood pool, which was determined by infusion of 99mTc-labeled rabbit erythrocytes. Blood pool and decay-corrected biodistribution data reveal the kinetics of LEH distribution, with an initial rapid uptake by the liver, 8% at 30 min and 15% at 2 hr. The spleen accumulates less LEH initially, 3% at 30 min and 7% at 2 hr, with an apparent linear uptake of LEH over this time period. Image biodistribution data was also validated at 20 hr by tissue sampling. At 20 hr postinfusion, autopsy biodistribution data reveals approximately 42.6% of the total counts remaining in the blood, 15.4% in the liver, 18.1% in spleen, 3.2% in the lungs, 2.4% in muscle, 1.6% in urine, and trace levels in the kidney, brain, and heart (less than 1%). There is no evidence of hemoglobin release from LEH or kidney dysfunction (normal creatinine and blood urea nitrogen) at any time over the course of the study.
authors.affiliation: Center for Biomolecular Science and Engineering, Naval Research Laboratory, Washington, DC 20375-5000.
authors.forename: A S
authors.initials: AS
authors.lastname: Rudolph
authors.forename: R W
authors.initials: RW
authors.lastname: Klipper
authors.forename: B
authors.initials: B
authors.lastname: Goins
authors.forename: W T
authors.initials: WT
authors.lastname: Phillips
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001802:Blood Substitutes / Q000493:pharmacokinetics*; D002417:Cattle; D004337:Drug Carriers; D006454:Hemoglobins / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D008657:Metabolic Clearance Rate; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010091:Oximes / Q000493:pharmacokinetics*; D011817:Rabbits; D013667:Technetium / Q000493:pharmacokinetics*; D019690:Technetium Tc 99m Exametazime; D014018:Tissue Distribution
chemical_list: D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D015609:Organotechnetium Compounds; D010091:Oximes; D019690:Technetium Tc 99m Exametazime; D013667:Technetium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase