Extended single-dose toxicity study of [211At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer

• DOI: 10.1007/s12149-021-01612-9
• Publication Date: 2021-04-19T15:04:38Z
• Authors: Tadashi Watabe; Kazuko Kaneda-Nak...; Kazuhiro Ooe; Yuwei Liu; Kenta Kurimoto; Takashi Murai; Yuka Shidahara; Kenji Okuma; Masanori Takeuchi; Masayuki Nishide; Atsushi Toyoshima; Atsushi Shinohara; Yoshifumi Shirakami
• Keywords: Radioiodine therapy

Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed extended single-dose toxicity examination under reliability standard, preclinical safety assessment [211At]NaAt determine FIH dose. solution was injected into normal 6-week-old mice (male (n = 50) female 50), body weight: male 33.2 ± 1.7 g, 27.3 1.5 g), which were then divided four groups: 5 MBq/kg 20), 20 50 30), saline control 30). The followed up days (primary evaluation point acute toxicity: n 80) or 14 20: recovery) monitor general condition weight change. At end observation period, necropsy, blood test, organ measurement, histopathological performed. For weight, statistical analyses compare data between groups. No abnormal findings observed mice. In group, males (days 3 5) showed significant decrease compared control. However, necropsy did not differ significantly beyond range spontaneous lesions. (50 MBq/kg) females white cell platelet counts on day 5, recovery 14. testis, considerable MBq/kg), multinucleated giant cells all mice, indicating change related administration [211At]NaAt. study [211At]NaAt, high doses resulted loss, transient bone marrow suppression, pathological changes require consideration trial.