Targeted therapy of colorectal cancer : preclinical evaluation of a radiolabelled antibody.

摘要: INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the antigen highly and homogenously expressed in >95% of all cancers, both primary tumors metastases. aim this study was to determine biodistribution tumor-targeting ability (177)Lu-labeled huA33. METHODS: huA33 labeled with beta-emitting therapeutic nuclide (177)Lu using chelator CHX-A"-DTPA, properties (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate determined vitro vivo nude mice xenografted SW1222 tumor cells. RESULTS: (177)Lu-huA33 bound specifically cancer cells (with K(D) value 2.3+/-0.3 nM, by saturation assay) vivo. uptake very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue low; radioactivity concentration blood (which had second highest concentration) lower than time points studied (8 10 days). tumor-to-blood ratio increased time, reaching 70+/-30, days pi. Throughout study, bone (known accumulate free (177)Lu) low, fraction protein-bound plasma samples high (95% 99%). This indicates stability CONCLUSION: shows favorable biodistribution, an impressively tumor-to-organ ratios, indicating that may be suitable for radioimmunotherapy cancer.