Background: Two-step targeting with bispecific antibody and Tc-labeled high-specific radioactivity polymers was used for molecular imaging of two very small model lesions in rats.
Methods and results: Sprague-Dawley rats (group I) were injected with surrogate antigen-coated beads (SA beads) in the right hind leg or unmodified beads in the contralateral hind leg. In group II, femoral artery de-endothelialization was induced in the left hind leg and sham operation was performed in the contralateral hind leg. Bispecific antibody Z2D3 F(ab')2-anti-DTPA F(ab')2 was injected intravenously 24 h after SAB injection or 1 week after endothelial denudation. Tc-labeled polymers were injected intravenously 24 h later and gamma-images obtained at 2 and 24 h in group I or approximately 2.5 h in group II. Lesions were visualized by 2 h. In group I, SA beads-specific uptake in muscles was significantly greater than with unmodified beads (P<0.015). In group II, lesions were visualized by 2.5 h after radiopolymer injection with uptake activity 2.1+/-0.6 times greater than in the contralateral side from in-vivo images (P<0.004) and 1.8+/-0.7 times by gamma-scintillation counting (P<0.04).
Conclusion: Pretargeting with Z2D3 bispecific antibody for the localization of radiolabeled polymers enabled successful in-vivo gamma-imaging of very small lesions in two rat models of extravascular and intravascular targets. Biodistribution data confirmed that pretargeting with bispecific antibody enabled targeted visualization of two different very small model lesions by in-vivo gamma-imaging.