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

Objective: We aimed to estimate in vivo At-labeled meta-benzylguanidine (At-MABG) absorbed doses by the two dose conversion methods, using I-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 At-MABG were calculated based on the medical internal radiation dose formalism with the conversion of the physical half-life time of I to that of At. 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 At-MABG and I-MIBG had similar properties of initial activity concentrations and biological components, but the basic method did not simulate the At-MABG dose. Simulated At-MABG doses from I-MIBG using the RAP method were in agreement with those from At-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 At-MABG absorbed doses from the pharmacokinetics of I-MIBG with some limitations. The RAP method would be applicable to a large number of subjects for targeted nuclide therapy.