TY - JOUR T1 - Imaging Experimental Atherosclerotic Lesions in ApoE Knockout Mice: Enhanced Targeting with Z<sub>2</sub>D<sub>3</sub>-Anti-DTPA Bispecific Antibody and <sup>99m</sup>Tc-Labeled Negatively Charged Polymers JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 868 LP - 876 VL - 47 IS - 5 AU - Ban-An Khaw AU - Yared Tekabe AU - Lynne L. Johnson Y1 - 2006/05/01 UR - http://jnm.snmjournals.org/content/47/5/868.abstract N2 - In vivo molecular imaging may be improved if specific radioactivity at the target site could be increased while maintaining low background activity. Bispecific antibody complexes and 99mTc-labeled negatively charged chelating polymers that react specifically with the capture arm of the bispecific antibody complex were used to demonstrate the feasibility of imaging very small atherosclerotic lesions in ApoE knockout mice. Methods: Left femoral artery denudation in ApoE−/− mice on a hyperlipidemic diet was used to induce accelerated atherosclerotic lesions. Approximately 40 μg of bispecific antibodies were injected intravenously after 2 wk of endothelial denudation. The next day, ∼15.0 MBq 99mTc-DTPA–succinyl-polylysine (2 μg; DTPA is diethylenetriaminepentaacetic acid) were injected intravenously. Results: In vivo γ-images showed that lesions were observed unequivocally by 2–3 h. Sham-operated right femoral regions showed no radiotracer accumulation. Ex vivo γ-scintillation counting corrected for sham-operated nonspecific activity and lesion mass showed that the mean lesion activity was 10.10 ± 6.76 %ID/g (percentage injected dose per gram), whereas nonspecific human IgG bispecific control (NSB control) also corrected similarly was 0.939 ± 0.877 %ID/g (P &lt; 0.03). Atherosclerotic lesions were confirmed by immunohistochemical staining. Computer planimetry of immunohistograms showed the mean lesion size to be 2.64 ± 2.46 mg. Conclusion: Use of bispecific antibody complexes and 99mTc-DTPA–succinyl-polylysine enabled in vivo visualization of very small atherosclerotic lesions in ApoE knockout mice. ER -