Chul-Hee Lee1,2,3,4, Ilhan Lim5,6, Sang-Keun Woo7,8, Wook Kim9, Kwang Il Kim9, Kyo Chul Lee9, Kanghyon Song10, Sang Moo Lim1. 1. Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. 2. Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea. 3. Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. 4. Department of Radiology, Weill Cornell Medicine, New York, New York, USA. 5. Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. ilhan@kcch.re.kr. 6. Department of Radiological and Medico-Oncological Sciences, University of Science and Technology, Seoul, Korea. ilhan@kcch.re.kr. 7. Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. skwoo@kirams.re.kr. 8. Department of Radiological and Medico-Oncological Sciences, University of Science and Technology, Seoul, Korea. skwoo@kirams.re.kr. 9. Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. 10. Department of Urology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Abstract
OBJECTIVE: The aim of this study was to evaluate the radiation dosimetry of alpha-emitter 225Ac-DOTA-rituximab using Monte Carlo simulation of 64Cu-DOTA-rituximab. METHODS: CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by 64Cu. 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 64Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. 225Ac-DOTA-rituximab tumor dosimetry was performed using Monte Carlo simulation with 64Cu-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 64Cu-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 64Cu-DOTA-rituximab was measured as the effective dose (1.07E-02 mSv/MBq). In the tumor region, equivalent doses of 225Ac-DOTA-rituximab (14 SvRBE5/MBq) were much higher (74-fold) than those of 64Cu-DOTA-rituximab (0.19 SvRBE5/MBq) (p < 0.01). CONCLUSION: Tumor dosimetry of 225Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of 64Cu-DOTA-rituximab. 225Ac-DOTA-rituximab can be employed for lymphoma as targeted alpha therapy.
OBJECTIVE: The aim of this study was to evaluate the radiation dosimetry of alpha-emitter 225Ac-DOTA-rituximab using Monte Carlo simulation of 64Cu-DOTA-rituximab. METHODS:CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by 64Cu. 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 64Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. 225Ac-DOTA-rituximabtumor dosimetry was performed using Monte Carlo simulation with 64Cu-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 64Cu-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 64Cu-DOTA-rituximab was measured as the effective dose (1.07E-02 mSv/MBq). In the tumor region, equivalent doses of 225Ac-DOTA-rituximab (14 SvRBE5/MBq) were much higher (74-fold) than those of 64Cu-DOTA-rituximab (0.19 SvRBE5/MBq) (p < 0.01). CONCLUSION:Tumor dosimetry of 225Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of 64Cu-DOTA-rituximab. 225Ac-DOTA-rituximab can be employed for lymphoma as targeted alpha therapy.
Entities:
Keywords:
225Ac; 64Cu; CD20-positive B-cell lymphoma; Monte Carlo simulation; PET; Rituximab
Authors: Paul E Borchardt; Rui R Yuan; Matthias Miederer; Michael R McDevitt; David A Scheinberg Journal: Cancer Res Date: 2003-08-15 Impact factor: 12.701
Authors: Ross C Larue; Enming Xing; Adam D Kenney; Yuexiu Zhang; Jasmine A Tuazon; Jianrong Li; Jacob S Yount; Pui-Kai Li; Amit Sharma Journal: Bioconjug Chem Date: 2020-12-24 Impact factor: 4.774