APRINOIA Therapeutics Inc., Tokyo, Japan.
Shiga Medical Center Research Institute, Moriyama, Japan.
Ann Nucl Med. 2023 May;37(5):300-309. doi: 10.1007/s12149-023-01828-x. Epub 2023 Mar 9.
Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. Florzolotau (18F) (florzolotau, APN-1607, PM-PBB3) has been shown to be a probe for tau fibrils in an animal model and patients with Alzheimer's disease and those with non-Alzheimer's disease tauopathies. The objective of this study is to evaluate the safety, pharmacokinetics, and radiation dose following a single intravenous administration of florzolotau in healthy Japanese subjects.
Three healthy male Japanese subjects aged between 20 and 64 were enrolled in this study. Subjects were determined to be eligible based on the screening assessments at the study site. Subjects received a single intravenous dose of 195.0 ± 0.5 MBq of florzolotau and underwent the whole-body PET scan 10 times in total to calculate absorbed doses to major organs/tissues and effective dose. Radioactivities in whole blood and urine were also measured for pharmacokinetic evaluation. Absorbed doses to major organs/tissues and effective dose were estimated using the medical internal radiation dose (MIRD) method. Vital signs, electrocardiography (ECG), and blood tests were done for safety evaluation.
The intravenous injection of florzolotau was well tolerated. There were no adverse events or clinically detectable pharmacologic effects related to the tracer in any subjects. No significant changes in vital signs and ECG were observed. The highest mean initial uptake at 15 min after injection was in the liver (29.0 ± 4.0%ID), intestine (4.69 ± 1.65%ID), and brain (2.13 ± 0.18%ID). The highest absorbed dose was 508 μGy/MBq of the gallbladder wall, followed by the liver of 79.4 μGy/MBq, the pancreas of 42.5 μGy/MBq, and the upper large intestine of 34.2 μGy/MBq. The effective dose was calculated as 19.7 μSv/MBq according to the tissue weighting factor reported by ICRP-103.
Florzolotau intravenous injection was well tolerated in healthy male Japanese subjects. The effective dose was determined as 3.61 mSv when 185 MBq florzolotau was given.
在各种神经退行性疾病中，tau 的异常聚集是一个主要的致病因素。在动物模型和阿尔茨海默病患者以及非阿尔茨海默病 tau 病患者中，氟唑拉赞（18F）（氟唑拉赞、APN-1607、PM-PBB3）已被证明是 tau 原纤维的探针。本研究的目的是评估单次静脉注射氟唑拉赞在健康日本受试者中的安全性、药代动力学和辐射剂量。
本研究纳入了 3 名年龄在 20 至 64 岁之间的健康日本男性受试者。根据研究现场的筛查评估，确定受试者符合入选标准。受试者接受了单次静脉注射 195.0±0.5MBq 的氟唑拉赞，并进行了总共 10 次全身 PET 扫描，以计算主要器官/组织的吸收剂量和有效剂量。还测量了全血和尿液中的放射性以进行药代动力学评估。使用医学内部辐射剂量（MIRD）方法估算主要器官/组织的吸收剂量和有效剂量。使用生命体征、心电图（ECG）和血液检查进行安全性评估。
静脉注射氟唑拉赞的耐受性良好。在任何受试者中，均未观察到与示踪剂相关的不良事件或临床可检测的药理作用。生命体征和心电图无明显变化。注射后 15 分钟时初始摄取最高的平均值为肝脏（29.0±4.0%ID）、肠道（4.69±1.65%ID）和大脑（2.13±0.18%ID）。胆囊壁的最高吸收剂量为 508μGy/MBq，其次是肝脏的 79.4μGy/MBq、胰腺的 42.5μGy/MBq 和大肠上部的 34.2μGy/MBq。根据 ICRP-103 报告的组织权重因子，有效剂量计算为 19.7μSv/MBq。
在健康的日本男性受试者中，静脉注射氟唑拉赞具有良好的耐受性。当给予 185MBq 的氟唑拉赞时，有效剂量确定为 3.61mSv。
