title: Comparative evaluation of 99Tcm-Hynic-HSA and 99Tcm-MAG3-HSA as possible blood pool agents.
abstract: Two strategies have been used to increase the 99Tcm binding strength of human serum albumin (HSA) and thus enhance its blood retention. In a first approach, HSA was derivatized with a varying number of hydrazino nicotinyl (Hynic) side-chains using N-hydroxysuccinimidyl hydrazino nicotinate. Labelling of this albumin derivative with 99Tcm resulted in labelling yields of 90-95%. On the other hand, a 99Tcm-MAG3-HSA conjugate was prepared using the preformed chelate approach. In this way, non-specific binding of 99Tcm to HSA could be excluded. The in vitro stability of both 99Tcm-HSA derivatives was evaluated by cysteine challenge experiments and revealed a much higher stability for 99Tcm-Hynic-HSA than for 99Tcm-MAG3-HSA. The biological behaviour of the preparations was evaluated in mice and a rabbit using 125I-HSA as an internal biological standard. The blood retention of 99Tcm-MAG3-HSA decreased more rapidly than that of 125I-HSA in both animal species, whereas 99Tcm-Hynic-HSA seemed to provide a quasi-perfect 99Tcm-labelled analogue for 125I-HSA and 99Tcm-red blood cells (99Tcm-RBCs). In addition, the blood retention of 99Tcm-Hynic-HSA appeared to be similar to that of 99Tcm-RBCs in a volunteer. These results clearly indicate the superiority of 99Tcm-Hynic-HSA over 99Tcm-MAG3-HSA as a possible blood pool agent.
authors.affiliation: Laboratory of Radiopharmaceutical Chemistry, FFW, K.U. Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Verbeke
authors.forename: O
authors.initials: O
authors.lastname: Hjelstuen
authors.forename: E
authors.initials: E
authors.lastname: Debrock
authors.forename: B
authors.initials: B
authors.lastname: Cleynhens
authors.forename: M
authors.initials: M
authors.lastname: De Roo
authors.forename: A
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D004912:Erythrocytes; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011817:Rabbits; D013668:Technetium Tc 99m Aggregated Albumin / Q000138:chemical synthesis / Q000493:pharmacokinetics; D017263:Technetium Tc 99m Mertiatide / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D013668:Technetium Tc 99m Aggregated Albumin; C098309:technetium Tc 99m hydrazino nicotinyl-human serum albumin; D017263:Technetium Tc 99m Mertiatide