We aimed to estimate in vivo 211At-labeled meta-benzylguanidine (211At-MABG) absorbed doses by the two dose conversion methods, using 131I-MIBG biodistribution data from a previously reported neuroblastoma xenograft model. In addition, we examined the effects of different cell lines and time limitations using data from two other works.
We used the framework of the Monte Carlo method to create 3200 virtual experimental data sets of activity concentrations (kBq/g) to get the statistical information. Time activity concentration curves were produced using the fitting method of a genetic algorithm. The basic method was that absorbed doses of 211At-MABG were calculated based on the medical internal radiation dose formalism with the conversion of the physical half-life time of 131I to that of 211At. We have further improved the basic method; that is, a novel dose conversion method, RAP (Ratio of Pharmacokinetics), using percent injected dose/g.
Virtual experiments showed that 211At-MABG and 131I-MIBG had similar properties of initial activity concentrations and biological components, but the basic method did not simulate the 211At-MABG dose. Simulated 211At-MABG doses from 131I-MIBG using the RAP method were in agreement with those from 211At-MABG, so that their boxes overlapped in the box plots. The RAP method showed applicability to the different cell lines, but it was difficult to predict long-term doses from short-term experimental data.
The present RAP dose conversion method could estimate 211At-MABG absorbed doses from the pharmacokinetics of 131I-MIBG with some limitations. The RAP method would be applicable to a large number of subjects for targeted nuclide therapy.
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The authors thank the project members of the medical radioisotope application for their kind assistance and wish to thank Dr. T. Sato (JAEA, Japan) for his early involvement in the conceptualization of MIRD formalism. This study was supported in part by KAKENHI (JP19H04296) from the Japan Society for the Promotion of Science to Dr. N. Suzui.
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Sakashita, T., Watanabe, S., Hanaoka, H. et al. Absorbed dose simulation of meta-211At-astato-benzylguanidine using pharmacokinetics of 131I-MIBG and a novel dose conversion method, RAP. Ann Nucl Med 35, 121–131 (2021). https://doi.org/10.1007/s12149-020-01548-6
- Targeted alpha therapy
- Dose conversion
- MIRD calculation
- Monte Carlo simulation