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用于肝癌放射性栓塞治疗的钬标记微球的制备及初步体内评估

Preparation and preliminary in vivo evaluation of Ho-labeled microspheres for possible use in radioembolic therapy of liver cancer.

作者信息

Subramanian Suresh, Vimalnath K V, Dash Ashutosh

机构信息

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.

出版信息

J Labelled Comp Radiopharm. 2018 May 30;61(6):509-514. doi: 10.1002/jlcr.3616. Epub 2018 Mar 12.

DOI:10.1002/jlcr.3616
PMID:29462501
Abstract

Hepatocellular carcinoma (HCC) or liver cancer is an increasingly prevalent and highly morbid disease with critical significance in the Asian and African subcontinents. Among the various therapies currently used in the clinic to combat the global menace of HCC, radioembolization with suitable therapeutic isotopes is an effective targeted approach. In the Indian context, the significant cost and logistical disadvantage of imported radioembolic formulations for HCC therapy make it essential to develop more feasible indigenous alternatives-using locally available radioisotopes and microspheric carriers-that can serve the nuclear medicine community. With this aim Ho-166 was produced with good specific activity (>13 GBq mg ) and purity (>99%) by reactor irradiation. Various commercially available microspheres were labeled with this therapeutic radioisotope, characterized for yield and stability of the radiolabeling, and tested for their in vivo retention and stability in Wistar rat model by viable surgery. Under the optimized reaction conditions, Ho-labeled microspheres were prepared with high yield (>94%-99%) and in vitro stability (>95%) in saline and serum. Retention studies in animal model showed that Ho-labeled microspheres remained stable in vivo and showed excellent retention in the site of interest (~95% at 72-hour p.i.). The study indicates good potential and warrants further investigation for application of these indigenous radiolabeled microspheres for HCC therapy. The successful application of this technology in the clinic would lead to logistically advantageous and cost-effective indigenous alternatives to expensive imported therapeutic solutions.

摘要

肝细胞癌(HCC)或肝癌是一种在亚洲和非洲次大陆日益普遍且具有高度致病性的疾病,具有至关重要的意义。在目前临床上用于对抗全球HCC威胁的各种疗法中,使用合适治疗性同位素的放射性栓塞是一种有效的靶向方法。在印度,用于HCC治疗的进口放射性栓塞制剂成本高昂且存在后勤方面的劣势,因此开发更可行的本土替代方案至关重要,即使用当地可得的放射性同位素和微球载体,以服务核医学界。出于这一目的,通过反应堆辐照制备出了具有良好比活度(>13 GBq/mg)和纯度(>99%)的Ho-166。用这种治疗性放射性同位素标记了各种市售微球,对放射性标记的产率和稳定性进行了表征,并通过活体手术在Wistar大鼠模型中测试了它们在体内的滞留情况和稳定性。在优化的反应条件下,制备出了Ho标记的微球,其在盐溶液和血清中的产率较高(>94%-99%)且体外稳定性良好(>95%)。动物模型中的滞留研究表明,Ho标记的微球在体内保持稳定,在感兴趣部位显示出优异的滞留情况(注射后72小时约为95%)。该研究表明这些本土放射性标记微球具有良好的应用潜力,值得进一步研究用于HCC治疗。这项技术在临床上的成功应用将带来后勤方面具有优势且成本效益高的本土替代方案,以替代昂贵的进口治疗方案。

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