Tumor-specific imaging with radiolabeled human anti-transferrin receptor antibody in pancreatic cancer mouse model

We radiolabeled the antibody with 125I by the chloramine-T method, and with 67Ga or 89Zr using deferoxamine. We conducted in vitro cell binding and competitive inhibition assays using a human pancreatic carcinoma cell line, MIAPaCa-2, which highly expressed TfR and a mouse fibroblast cell line A4, which highly expressed human HER2 but not human TfR. We inoculated MIAPaCa-2 and A4 cells subcutaneously into each side of hind limb and conducted PET imaging from one to six days postinjection of the 89Zr-labeled antibody. The cell binding assay showed that radiolabeled antibodies specifically bound to MIAPaCa-2 cells, but not to A4 cells. The Bmax of 125I-, 67Ga- and 89Zr-labeled antibodies was 69, 86 and 64 %, respectively. The competitive inhibition assay showed that Kd of 125I-labeled antibodies was 2 nM, respectively. Temporal PET imaging with the 89Zr -labeled antibody showed that the MIAPaca-2 tumor was readily visualized on day 1 postinjection and became clearer thereafter, and the uptake in the MIAPaca-2 tumor increased with time and reached 24.8% of injected dose per gram on day 6, whereas that in the A4 tumor was low and decreased with time. In conclusion, the radiolabeled anti-TfR antibody could be applicable for TfR-specific PET imaging and help in selecting appropriate patients for TfR-targeted treatments.14th International Congress of Radiation Research(ICRR’2011