@misc{oai:repo.qst.go.jp:00076187,
 author = {Yoshinaga, Keiichiro and Zhao, Songji and Washino, Komei and Aoki, Miho and Ken-ichi, Nishijima and Shimoyama, Saki and Ukon, Naoyuki and Tan, Chengbo and Washiyama, Kohshin and Takahashi, Kazuhiro and Ito, Hiroshi and Higashi, Tatsuya and Yoshinaga, Keiichiro and Washino, Komei and Higashi, Tatsuya},
 month = {Jun},
 note = {Abstract
Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma, new effective approaches are being sought. The alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) has potential as a metastatic pheochromocytoma treatment. We previously reported the tumor volume reduction effects of 211At-MABG in a PC12 pheochromocytoma mouse model. As 211At-MABG does not emit gamma-rays suitable for dosimetry and imaging, 211At-MABG needs a companion diagnostic imaging agent such as 123I-meta-iodobenzylguanidine (123I-MIBG) to be used in making treatment decisions. However, the pharmacokinetics of 123I-MIBG as a companion drug for 211At-MABG radiotherapy have not been evaluated. The purpose of this study was to evaluate the similarities and differences between 123I-MIBG and 211At-MABG in biodistribution in normal mice under clinical conditions.
Methods: In this biodistribution study, male normal mice (BALB/cCrSlc, 9 weeks old) received intravenously either 997kBq of the carrier-added commercial 123I-MIBG or 483kBq of the non-carrier-added 211At-MABG. 123I-MIBG dosage was calculated based on the human clinical dose for diagnostic imaging (111MBq/60kg) on a body surface area basis, and 211At-MABG dosage was the complete remission dose identified in a PC12-xenografted mouse model. The mice were sacrificed at 1 min, 30 min, 1 h, 3 h, 6 h, 12 h and 24 h after two tracer injections (n = 5 in each group). Blood, brain, thyroid, heart, lung, liver, spleen, stomach, small intestine, pancreas, kidney, adrenal gland, muscle, bone, urine and feces were collected, weighed and measured for radioactivity using a gamma counter. The biodistribution of two drugs was statistically compared at 6 hours post intravenous tracer injection which is the expected time to acquire images in clinical settings.
Results: 211At-MABG and 123I-MIBG showed very similar biodistribution profiles in normal mice at every time point (see figure). Both drugs showed higher uptake in heart and adrenal glands. Specifically, at 6h, 123I-MIBG and 211At-MABG accumulation were similar in heart (15.5±1.5 vs. 18.1±2.8%ID/g, P=0.109) and adrenal gland (14.2±1.9 vs. 19.7±5.5%ID/g, P=0.067), respectively. 123I-MIBG showed lower uptake in lung (2.9±0.2 vs. 4.9±0.5%ID/g, P<0.0001) and liver (2.5±0.4 vs. 4.9±0.6%ID/g, P<0.0001) compared to 211At-MABG. In contrast, 123I-MIBG showed higher uptake in thyroid (0.53±0.21 vs. 0.20±0.07%ID, P=0.0090) than did 211At-MABG, suggesting that dehalogenation may occur more easily in 123I-MIBG than in 211At-MIBG. Total body excretion of 123I-MIBG at 24 h was higher than that of 211At-MABG (60.8±8.86% vs. 49.3±4.79%ID) (P=0.0328).
Conclusions: At each time point, the trends for biodistribution of 123I-MIBG and 211At-MABG were almost similar in normal mice. A certain level of difference was observed in heart and adrenal gland, which have higher density of noradrenalin transporter compared to other organs. 123I-MIBG may be used for dosimetry and imaging for decisions regarding treatment with 211At-MABG radiotherapy as a companion drug. Where organs showed a difference in the estimated absorbed dose uptake of the two tracers, 123I-MIBG biodistribution data needs certain adjustments to compensate for possible under- or over-estimation of 211At-MABG absorbed dose., SNMMI 2019 Annual Meeting},
 title = {Possibility of 123I-meta-iodobenzylguanidine (123I-MIBG) as companion diagnostic drug for therapeutic alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) in normal mice},
 year = {2019}
}