Comparative evaluation of 99Tcm-Hynic-HSA and 99Tcm-MAG3-HSA as possible blood pool agents.

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.