Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Nucl Med Biol. 2012 Jul;39(5):645-51. doi: 10.1016/j.nucmedbio.2011.12.001. Epub 2012 Feb 10.
We previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting.
Specific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus 111In-labeled cMORF to direct targeting by 111In-labeled HPi1.
HPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ 111In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting.
Pretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ.
我们之前展示了 MORF/cMORF 对人胰岛和贝塔洛克斯 5 细胞（一种人胰岛细胞系）的前靶向作用，这些细胞被移植到小鼠的皮下，使用的是抗人胰岛抗体 HPi1。现在，我们比较了前靶向与直接靶向在胰岛移植模型中的作用，以评估前靶向可以在多大程度上提高靶/非靶（T/NT）比值。
我们用抗人胰岛抗体 HPi1 特异性地结合移植到小鼠皮下的胰岛细胞，与阴性对照抗体进行比较。然后，我们比较了 MORF-HPi1 加 111In 标记的 cMORF 的前靶向与 111In 标记的 HPi1 的直接靶向。
通过免疫荧光，我们证明了 HPi1 与移植的贝塔洛克斯 5 细胞的结合。尽管靶标积累相似，但前靶向的正常器官 111In 背景始终较低。更重要的是，与直接靶向相比，前靶向的移植到胰腺和肝脏的比值分别为 26 和 10，而直接靶向的比值分别为 9 和 0.6。
前靶向大大提高了 T/NT 比值，并且基于胰腺内内分泌与外分泌的估计比值，前靶向可能接近在该器官内成功成像人胰岛所需的灵敏度。
