Human dosimetry of free (211)At and meta-[(211)At]astatobenzylguanidine ((211)At-MABG) estimated using preclinical biodistribution from normal mice

BACKGROUND: (211)At is one of the ideal nuclides for targeted radionuclide therapies (TRTs). Meta-[(211)At]astatobenzylguanidine ((211)At-MABG) has been proposed for the treatment of pheochromocytoma. To effectively use these radiopharmaceuticals, dosimetry must be performed. It is important to determine the absorbed doses of free (211)At and (211)At-MABG to determine the organs that may be at risk when using TRTs. The aim of this study was to estimate human dosimetry from preclinical biodistribution of free (211)At and (211)At-MABG in various organs in normal mice. METHODS: Male C57BL/6 N mice were administered 0.13 MBq of free (211)At or 0.20 MBq of (211)At-MABG by tail-vein injection. The mice were sacrificed at 5 min, and at 1, 3, 6, and 24 h after the injection (n = 5 for each group). The percentage of injected activity per mass in organs and blood (%IA/g) was determined. The human absorbed doses of free (211)At and (211)At-MABG were calculated using the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) version 2.0 and IDAC-Dose 2.1. RESULTS: High uptake of free (211)At was observed in the lungs, spleen, salivary glands, stomach, and thyroid. The absorbed doses of free (211)At in the thyroid and several tissues were higher than those of (211)At-MABG. The absorbed doses of (211)At-MABG in the adrenal glands, heart wall, and liver were higher than those of free (211)At. CONCLUSIONS: The absorbed doses of (211)At-MABG in organs expressing the norepinephrine transporter were higher than those of free (211)At. In addition, the biodistribution of free (211)At was different from that of (211)At-MABG. The absorbed dose of free (211)At may help predict the organs potentially at risk during TRTs using (211)At-MABG due to deastatination.