In vitro and in vivo characterization of 177Lu-huA33: A radioimmunoconjugate against colorectal cancer

IntroductionThe humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of 177Lu-labeled huA33.MethodshuA33 was labeled with the β-emitting therapeutic nuclide 177Lu using the chelator CHX-Aʺ-DTPA, and the properties of the 177Lu-CHX-Aʺ-huA33 (177Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells.ResultsThe 177Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a KD value of 2.3±0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of 177Lu-huA33 was very high, peaking at 134±21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70±30, 10 days pi. Throughout the study, the uptake of 177Lu in bone (known to accumulate free 177Lu) was low, and the fraction of protein-bound 177Lu in plasma samples was high (95% to 99%). This indicates high stability of the 177Lu-huA33 conjugate in vivo.ConclusionThe 177Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.