Tekabe Yared, Einstein Andrew J, Johnson Lynne L, Khaw Ban-An
Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Nucl Med Commun. 2010 Apr;31(4):320-7. doi: 10.1097/MNM.0b013e32833576e8.
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.
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).
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.
采用双特异性抗体和锝标记的高特异性放射性聚合物进行两步靶向，用于大鼠体内两个非常小的模型病灶的分子成像。
将替代抗原包被的珠子（SA珠子）注射到斯普拉格-道利大鼠（I组）的右后肢，对侧后肢注射未修饰的珠子。在II组中，左后肢诱导股动脉去内皮化，对侧后肢进行假手术。在注射SA珠子后24小时或内皮剥脱后1周静脉注射双特异性抗体Z2D3 F(ab')2-抗-DTPA F(ab')2。24小时后静脉注射锝标记的聚合物，I组在2小时和24小时获取γ图像，II组在约2.5小时获取γ图像。2小时时可观察到病灶。在I组中，SA珠子在肌肉中的特异性摄取显著高于未修饰的珠子（P<0.015）。在II组中，注射放射性聚合物后2.5小时可观察到病灶，体内图像显示摄取活性比另一侧高2.1±0.6倍（P<0.004），γ闪烁计数显示高1.8±0.7倍（P<0.04）。
用Z2D3双特异性抗体进行预靶向以定位放射性标记的聚合物，能够在两种血管外和血管内靶点的大鼠模型中成功实现非常小的病灶的体内γ成像。生物分布数据证实，用双特异性抗体进行预靶向能够通过体内γ成像对两种不同的非常小的模型病灶进行靶向可视化。
