Targeted alpha immunotherapy of CD20-positive B-cell lymphoma model: dosimetry estimate of Ac-DOTA-rituximab using Cu-DOTA-rituximab.

OBJECTIVE

The aim of this study was to evaluate the radiation dosimetry of alpha-emitter Ac-DOTA-rituximab using Monte Carlo simulation of Cu-DOTA-rituximab.

METHODS

CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by Cu. Tumor xenograft models were established in BALB/c-nu mice. Animal PET/CT imaging was obtained after tail vein injection with and without a pre-dose of 2 mg of cold rituximab. Specific binding of tumors was evaluated by an organ distribution assay and autoradiography. CD20 expression in tumor tissues was evaluated by immunohistochemistry. The residence time was calculated using Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. Ac-DOTA-rituximab tumor dosimetry was performed using Monte Carlo simulation with Cu-DOTA-rituximab PET/CT images.

RESULTS

Specific binding of Raji cells (CD20 positive) was 90 times that of Jurkat cells (CD20 negative) (p < 0.0001). Immunoreactivity was more than 75%. PET/CT imaging with Cu-DOTA-rituximab was specifically observed in tumors. The radioactivity of the tumor was much higher than that of other organs, and tumor uptake was related to CD20 expression. The predicted human dose for the administration of Cu-DOTA-rituximab was measured as the effective dose (1.07E-02 mSv/MBq). In the tumor region, equivalent doses of Ac-DOTA-rituximab (14 Sv/MBq) were much higher (74-fold) than those of Cu-DOTA-rituximab (0.19 Sv/MBq) (p < 0.01).

CONCLUSION

Tumor dosimetry of Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of Cu-DOTA-rituximab. Ac-DOTA-rituximab can be employed for lymphoma as targeted alpha therapy.