Center for Molecular Imaging, Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nat Med. 2011 Dec 4;18(1):172-7. doi: 10.1038/nm.2590.
Studies of ligand-receptor binding and the development of receptor antagonists would benefit greatly from imaging techniques that translate directly from cell-based assays to living animals. We used Gaussia luciferase protein fragment complementation to quantify the binding of chemokine (C-X-C motif) ligand 12 (CXCL12) to chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. Studies established that small-molecule inhibitors of CXCR4 or CXCR7 specifically blocked CXCL12 binding in cell-based assays and revealed differences in kinetics of inhibiting chemokine binding to each receptor. Bioluminescence imaging showed CXCL12-CXCR7 binding in primary and metastatic tumors in a mouse model of breast cancer. We used this imaging technique to quantify drug-mediated inhibition of CXCL12-CXCR4 binding in living mice. We expect this imaging technology to advance research in areas such as ligand-receptor interactions and the development of new therapeutic agents in cell-based assays and small animals.
从基于细胞的测定法直接转化到活体动物的成像技术，将极大地促进配体-受体结合的研究和受体拮抗剂的开发。我们使用海肾荧光素酶蛋白片段互补来定量趋化因子（C-X-C 基元）配体 12（CXCL12）与趋化因子（C-X-C 基元）受体 4（CXCR4）和 CXCR7 的结合。研究证实，CXCR4 或 CXCR7 的小分子抑制剂可特异性地阻断基于细胞的测定法中 CXCL12 的结合，并揭示了抑制每种受体的趋化因子结合的动力学差异。生物发光成像显示，在乳腺癌小鼠模型中的原发和转移性肿瘤中存在 CXCL12-CXCR7 结合。我们使用这种成像技术在活体小鼠中定量测定药物介导的 CXCL12-CXCR4 结合抑制作用。我们期望这种成像技术能推进配体-受体相互作用等领域的研究，并在基于细胞的测定法和小动物中开发新的治疗剂。
