Abma E, Peremans K, De Vos F, Bosmans T, Kitshoff A M, Daminet S, Ni Y, Dockx R, de Rooster H
Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
Vet Comp Oncol. 2018 Sep;16(3):318-323. doi: 10.1111/vco.12381. Epub 2018 Jan 4.
Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of I-Hyp. Three healthy dogs were included. I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients.
金丝桃素（Hyp）是一种对坏死组织具有亲和力的化合物，可通过放射性碘进行有效标记，用于诊断和治疗目的。在将碘代金丝桃素（I-Hyp）视为犬类癌症患者联合治疗中的一种临床有用药物之前，有必要评估其毒性。本研究的目的是调查单次给药I-Hyp的生物分布和耐受性。纳入了三只健康犬。静脉注射剂量为0.2mg/kg、活度为185MBq的I-Hyp。对身体、血液学和生化参数的影响进行了表征，并评估了生物分布和消除模式、有效半衰期和剂量率。与药物相关的不良事件仅限于轻度胃肠道症状，在48小时内消退。治疗前后血液学和血清生化指标未发现显著差异。给药后，注射剂量的最高百分比（%ID±SD）出现在肝脏（5.5±0.33）、肺（4.17±0.14）和心脏（3.11±0.78）。24小时后，结肠（4.25±1.45）和肝脏（3.45±0.60）中的%ID最高。所有器官在7天内有效清除。有效半衰期确定为80小时，1天内1米处的剂量率降至<20μSv/h以下。目前的研究表明健康犬对所述剂量的I-Hyp单次给药耐受性良好，并支持在犬类癌症患者联合治疗中使用放射性碘化金丝桃素。
