PT  - JOURNAL ARTICLE
AU  - Komei Washino
AU  - Songji Zhao
AU  - Keiichiro Yoshinaga
AU  - Yoichi Ito
AU  - Miho Aoki
AU  - Naoyuki Ukon
AU  - Saki Shimoyama
AU  - Ken-ichi Nishijima
AU  - Kohshin Washiyama
AU  - Natsue Ito
AU  - Naho Yoshioka
AU  - Naomi Tamura
AU  - Kazuhiro Takahashi
AU  - Hiroshi Ito
AU  - Tatsuya Higashi
TI  - <strong>Differences and similarities in biodistribution, pharmacokinetics and metabolites of <sup>211</sup>At-MABG versus <sup>123</sup>I-MIBG in normal mice</strong>
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 1312--1312
VI  - 61
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/61/supplement_1/1312.short
4100  - http://jnm.snmjournals.org/content/61/supplement_1/1312.full
SO  - J Nucl Med2020 May 01; 61
AB  - 1312Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. A radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL. The alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) has strong cell-injury effects but may be a potential therapy for metastatic PPGL. Before radiopharmaceutical development of 211At-MABG for clinical application can take place, its pharmacokinetic profile and metabolites must be established. Therefore, the purpose of the study was to evaluate the differences and similarities in biodistribution, pharmacokinetics and metabolites of 211At-MABG versus 123I-MIBG in normal mice. Methods: Male normal mice (BALB/c, 9 weeks) received either 0.997 MBq of 123I-MIBG (equivalent to a human clinical imaging dose) or 0.483 MBq of 211At-MABG (a therapeutic dose in xenografted mouse model) intravenously. Mice were sacrificed by whole blood collection from the heart under anesthesia and dissected at 7 time points from 1 minute to 24 hours after radiotracer administration (n=5/group). We collected feces and urine to evaluate whole-body excretion of 211At-MABG and 123I-MIBG during the 24 hours after administration and counted the radioactivity therein using a γ-counter. Organs were weighed and their radioactivity was measured as the percentage of injected dose per gram of tissue (%ID/g). The removed whole blood was separated into blood cells and plasma fractions. Plasma was further separated into protein and non-protein fractions by adding cold ethanol. Radioactivity of these fractions was also measured with the γ-counter. Results: 211At-MABG and 123I-MIBG showed similar biodistribution until 24 hours. %ID in feces and urine representing whole body excretion was 49.25±4.79% for 211At-MABG and 60.86±8.86% for 123I-MIBG, respectively (P=0.033). The blood clearance was very similar in the two drugs until 6 hours after intravenous administration. The early-phase half-life (T(α)1/2) of the blood time-activity curve was 10.77 minutes for 211At-MABG and 11.76 minutes for 123I-MIBG (P= 0.231). On the other hand, the late-phase half-life (T(β)1/2) was 13.63 hours for 211At-MABG and 7.29 hours for 123I-MIBG (P=0.017). The area under curve (AUC) of the blood time-activity curve from 1 minute to 24 hours was 581 %ID/g･min for 211At-MABG and 483 %ID/g･min for 123I-MIBG. At 30 min, 29.3±3.4% of radioactivity was present in plasma fractions for 211At-MABG, versus 46.5±8.1% in plasma fractions for 123I-MIBG (P=0.002). Conclusions: At each time point, the trends for biodistribution of 211At-MABG and 123I-MIBG were similar in normal mice. Excretion of 211At-MABG was slower than that of 123I-MIBG, suggesting that 211At-MABG may be less susceptible to metabolism in normal mice. Based on the biodistribution, pharmacokinetic and metabolic profile of 211At-MABG, 211At-MABG may be suitable as a treatment option for metastatic pheochromocytoma and paraganglioma similar to 131I-MIBG.