Two-step targeting of xenografted colon carcinoma using a bispecific antibody and Re-188-labeled bivalent hapten: Biodistribution and dosimetry studies

Radioimmunotherapy (RIT) is currently being considered for the treatment of solid tumors. Although results have been encouraging for pretargeted(131)l RIT with the affinity enhancement system (AES), the radionuclide used is n ot optimal because of its long half-life, strong gamma emission, poor speci fic activity, end low beta particle energy. Re-188, though unsuitable for d irect antibody labeling, could be used with the AES two-step targeting tech nique. The purpose of this study was to compare the distribution and dosime try of a bivalent hapten labeled with Re-188 or (125)l. For dosimetry calcu lations and biodistribution data, (125)l was substituted far (131)l. Method s: After preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody (Bs-mAb F6-679), AG 8.1 or AG 8.0 hapten radi olabeled with Re-188 or (125)l was injected into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressin g CEA. A dosimetry study was performed for each animal from the concentrati on of radioactivity in tumor and different tissues. Results: Radiolabeling of AG 8.1 with (125)l afforded a 40% yield with a specific activity of 11.1 MBq/nmol after purification. Radiolabeling of AG 8.0 with Re-188 afforded a 72% yield with a specific activity of 31.82 MBq/nmol. In all experiments, the percentage of tumor uptake of (125)l-AG 8.1 was always significantly g reater than that of Re-188-AG 8.0. The corresponding tumor-to-tissue ratios reflected uptake values. The least favorable tumor-to-normal tissue ratios in the dosimetry study were 8.1 and 8.5 for (131)l (tumor-to-blood ratio a nd tumor-to-kidney ratio, respectively) and 2.3 for Re-188 (tumor-to-intest ine ratio). Conclusion: This study indicates that 188Re can be used for rad iolabeling of hapten in two-step radioimmunotherapy protocols with the AES technique. Re-188 has a greater range than (131)l, which should allow the t reatment of solid tumors around 1 cm in diameter. Although the method used for hapten radiolabeling did not provide optimal tumor uptake, the use of a bifunctional chelating agent associated with AG 8.1 should solve this prob lem.