Absorbed dose simulation of meta-211At-astato-benzylguanidine using pharmacokinetics of 131I-MIBG and a novel dose conversion method, RAP

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

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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References

  1. 1.

    Higashi T, Kudo T, Kinuya S. Radioactive iodine (131I) therapy for differentiated thyroid cancer in Japan: current issues with historical review and future perspective. Ann Nucl Med. 2012;26:99–112.

    CAS  Article  Google Scholar 

  2. 2.

    Shinohara A, Hanaoka H, Sakashita T, Sato T, Yamaguchi A, Ishioka NS, Tsushima Y. Rational evaluation of the therapeutic effect and dosimetry of auger electrons for radionuclide therapy in a cell culture model. Ann Nucl Med. 2018;32:114–22.

    CAS  Article  Google Scholar 

  3. 3.

    Conti M, Eriksson L. Physics of pure and non-pure positron emitters for PET: a review and a discussion. EJNMMI Phys. 2016;3:8.

    Article  Google Scholar 

  4. 4.

    Elgqvist J, Frost S, Pouget JP, Albertsson P. The potential and hurdles of targeted alpha therapy—clinical trials and beyond. Front Oncol. 2014;3:324.

    Article  Google Scholar 

  5. 5.

    Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, Kopka K, Apostolidis C, Haberkorn U, Morgenstern A. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer. J Nucl Med. 2016;57:1941–4.

    CAS  Article  Google Scholar 

  6. 6.

    Ohshima Y, Sudo H, Watanabe S, Nagatsu K, Tsuji AB, Sakashita T, Ito YM, Yoshinaga K, Higashi T, Ishioka NS. Antitumor effects of radionuclide treatment using α-emitting meta-211At-astato-benzylguanidine in a PC12 pheochromocytoma model. Eur J Nucl Med Mol Imaging. 2018;45:999–1010.

    CAS  Article  Google Scholar 

  7. 7.

    Ohshima Y, Kono N, Yokota Y, Watanabe S, Sasaki I, Ishioka NS, Sakashita T, Arakawa K. Anti-tumor effects and potential therapeutic response biomarkers in α-emitting meta-211At-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing. Theranostics. 2019;9:1538–49.

    CAS  Article  Google Scholar 

  8. 8.

    Vaidyanathan G, Friedman HS, Keir ST, Zalutsky MR. Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model. Nucl Med Biol. 1996;23:851–6.

    CAS  Article  Google Scholar 

  9. 9.

    Johnson EL, Turkington TG, Jaszczak RJ, Gilland DR, Vaidyanathan G, Greer KL, Coleman RE, Zalutsky MR. Quantitation of 211At in small volumes for evaluation of targeted radiotherapy in animal models. Nucl Med Biol. 1995;22:45–54.

    CAS  Article  Google Scholar 

  10. 10.

    Cederkrantz E, Andersson H, Bernhardt P, Bäck T, Hultborn R, Jacobsson L, Jensen H, Lindegren S, Ljungberg M, Magnander T, Palm S, Albertsson P. Absorbed doses and risk estimates of 211At-MX35 F(ab’)2 in intraperitoneal therapy of ovarian cancer patients. Int J Radiat Oncol Biol Phys. 2015;93:569–76.

    CAS  Article  Google Scholar 

  11. 11.

    Turkington TG, Zalutsky MR, Jaszczak RJ, Garg PK, Vaidyanathan G, Coleman RE. Measuring astatine-211 distributions with SPECT. Phys Med Biol. 1993;38:1121–30.

    CAS  Article  Google Scholar 

  12. 12.

    Nagao Y, Yamaguchi M, Watanabe S, Ishioka NS, Kawachi N, Watabe H. Astatine-211 imaging by a Compton camera for targeted radiotherapy. Appl Radiat Isot. 2018;139:238–43.

    CAS  Article  Google Scholar 

  13. 13.

    van Hulsteijn LT, Niemeijer ND, Dekkers OM, Corssmit EP. 131I-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta-analysis. Clin Endocrinol. 2014;80:487–501.

    Article  Google Scholar 

  14. 14.

    Hjornevik T, Martinsen AC, Hagve SE, Andersen MW, Mørk AC, Fjeld JG, Ruud E. Experiences from introducing standardized high dose 131I-mIBG treatment of children with refractory neuroblastoma: differences in effective dose to patients and exposure to caregivers. J Nucl Med Radiat Ther. 2015;6:6.

    Article  Google Scholar 

  15. 15.

    Carrasquillo JA, Pandit-Taskar N, Chen CC. I-131 metaiodobenzylguanidine therapy of pheochromocytoma and paraganglioma. Semin Nucl Med. 2016;46:203–14.

    Article  Google Scholar 

  16. 16.

    Watanabe S, Hanaoka H, Liang JX, Iida Y, Endo K, Ishioka NS. PET imaging of norepinephrine transporter-expressing tumors using 76Br-meta-bromobenzylguanidine. J Nucl Med. 2010;51:1472–9.

    CAS  Article  Google Scholar 

  17. 17.

    Hassanat A, Almohammadi KA, Alkafaween E, Abunawas E, Hammouri A, Prasath VB. Choosing mutation and crossover ratios for genetic algorithms—a review with a new dynamic approach. Information. 2019;10:390.

    Article  Google Scholar 

  18. 18.

    Erwin WD, Groch MW, Macey DJ, DeNardo GL, DeNardo SJ, Shen S. A radioimmunoimaging and MIRD dosimetry treatment planning program for radioimmunotherapy. Nucl Med Biol. 1996;23:525–32.

    CAS  Article  Google Scholar 

  19. 19.

    Spetz J, Rudqvist N, Forssell-Aronsson E. Biodistribution and dosimetry of free 211At, 125I- and 131I- in rats. Cancer Biother Radiopharm. 2013;28:657–64.

    CAS  Article  Google Scholar 

  20. 20.

    Sato T, Iwamoto Y, Hashimoto S, Ogawa T, Furuta T, Abe S, Kai T, Tsai PE, Matsuda N, Iwase H, Shigyo N, Sihver L, Niita K. Features of particle and heavy ion transport code system (PHITS) version 3.02. J Nucl Sci Technol. 2018;55:684–90.

  21. 21.

    Garg PK, Garg S, Zalutsky MR. Synthesis and preliminary evaluation of para- and meta-[18F]fluorobenzylguanidine. Nucl Med Biol. 1994;21:97–103.

    CAS  Article  Google Scholar 

  22. 22.

    Meyer GJ. Astatine. J Labelled Compd Radiopharm. 2018;61:154–64.

    CAS  Article  Google Scholar 

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Acknowledgments

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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Correspondence to Tetsuya Sakashita.

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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

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Keywords

  • Targeted alpha therapy
  • Dose conversion
  • Biodistribution
  • MIRD calculation
  • Monte Carlo simulation