Abstract
Purpose: To evaluate the radiation dosimetry of 225 Ac-DOTA-rituximab using Monte Carlo simulation of 64 Cu-DOTA-rituximab.Methods: CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by 64 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 64 Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. 225 Ac-DOTA-rituximab dosimetry analysis was performed using Monte Carlo simulation.Results: CD20 protein was highly expressed in Raji cells. Specific binding of Raji cells was 90 times that of Jurkat cells (p<0.0001). Immunoreactivity was more than 75%. PET/CT imaging with 64 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 64 Cu-DOTA-rituximab was measured as the effective dose (3.20E-02 mSv/MBq). In the tumor region, equivalent doses of 225 Ac-DOTA-rituximab (14 Sv RBE5 /MBq) were much higher (74-fold) than those of 64 Cu-DOTA-rituximab (0.19 Sv RBE5 /MBq) ( p<0.01 ).Conclusion: Tumor dosimetry of 225 Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of 64 Cu-DOTA-rituximab. 225 Ac-DOTA-rituximab can be used as targeted alpha therapy for patients with refractory lymphoma.
Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with15O-Gas Inhalation