生物 300：急性辐射综合征的预防性辐射对策。

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

机构信息

Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

出版信息

Mil Med. 2024 Aug 19;189(Suppl 3):390-398. doi: 10.1093/milmed/usae156.

DOI:10.1093/milmed/usae156

PMID:39160790

Abstract

INTRODUCTION

Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation.

MATERIALS AND METHODS

Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder.

RESULTS

In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls.

CONCLUSIONS

BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

摘要

简介

暴露于高剂量电离辐射会导致造血急性辐射综合征。目前，美国食品和药物管理局尚未批准任何可在辐射暴露前用于保护暴露个体的辐射医学对策。在这里，我们旨在评估合成金雀异黄素纳米颗粒（BIO 300）水混悬剂作为一种放射防护剂的治疗潜力，在使用非人类灵长类动物全身照射模型的初步功效研究中。

材料和方法

将 8 只恒河猴分为两组；四组接受载体，四组接受 BIO 300 注射混悬液，在 5.8Gy 全身照射前 24 小时。在研究的 60 天内监测生存、血细胞计数、血液化学和临床参数。在 60 天辐照后或根据未计划的安乐死标准死亡的动物采集组织，并进行组织病理学分析。分析的组织包括十二指肠、空肠、回肠、胸骨、肺、心脏、肝脏、肾脏、脾脏、肠道相关淋巴组织和膀胱。

结果

在这项初步研究中，所有接受 BIO 300 注射混悬液治疗的动物均存活至第 60 天，而仅 50%接受载体治疗的动物存活。我们发现，BIO 300 注射混悬液并没有改善血细胞计数（如中性粒细胞、血小板、白细胞）。然而，BIO 300 注射混悬液治疗的动物发热和发热性中性粒细胞减少症的发生率较低，辐射暴露后能够更好地保持体重，贫血程度较低，从贫血中恢复较快。组织病理学分析显示，与载体对照组相比，BIO 300 治疗的动物胸骨和其他组织的辐射损伤较小。