Possibility of 123I-meta-iodobenzylguanidine (123I-MIBG) as companion diagnostic drug for therapeutic alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) in normal mice
AbstractObjectives: 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 Meetin
