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

Abstract

Abstract 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.

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