Targeted alpha immunotherapy of CD20-positive B-cell lymphoma model: dosimetry estimate of 225Ac-DOTA-rituximab using 64Cu-DOTA-rituximab

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.

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Acknowledgements

This study was supported by a Grant from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT, Republic of Korea (No. 50547-2020) and the National Research Foundation of Korea (NRF) Grant funded by the Korea government (Ministry of Science and ICT) (No. 2019M2D2A1A02057204, 2020R1A2C2102492).

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This study was designed by C-HL, IL, S-KW, WK, KIK, KCL, KS, and SML. Data acquisition and analysis was performed by C-HL, WK, and S-KW. C-HL and IL wrote the manuscript draft. All authors reviewed and edited this final version of the manuscript.

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Correspondence to Ilhan Lim or Sang-Keun Woo.

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Lee, CH., Lim, I., Woo, SK. et al. Targeted alpha immunotherapy of CD20-positive B-cell lymphoma model: dosimetry estimate of 225Ac-DOTA-rituximab using 64Cu-DOTA-rituximab. Ann Nucl Med (2021). https://doi.org/10.1007/s12149-021-01607-6

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Keywords

  • CD20-positive B-cell lymphoma
  • Rituximab
  • 64Cu
  • PET
  • Monte Carlo simulation
  • 225Ac