骨肉瘤(OS)是儿童中最常诊断的骨癌,在过去的几十年中总体生存率几乎没有改善。二唾液酸神经节苷脂GD2在OS肿瘤上的高表面表达和在正常组织中的限制性表达使其成为抗OS放射性药物的理想靶标。由于人类和犬OS具有许多生物学和分子特征,犬科动物自发发生的OS一直是测试人类翻译的新成像和治疗方式的理想模型。在这项研究中,我们评估了人源化抗GD2抗体,hu3F8,作为一种潜在的递送载体,用于人和犬OS的靶向放射性药物成像。
通过免疫组织化学和流式细胞术检查hu3F8与人和犬OS细胞和肿瘤的交叉反应性。hu3F8用铟-111放射性标记,并在荷瘤异种移植物小鼠中评估[111In]In-hu3F8的生物分布。在自发性OS犬科动物中测试了[111In]In-hu3F8对转移性OS的靶向能力。
hu3F8以高结合亲和力与人和犬OS细胞以及犬OS肿瘤交叉反应。生物分布研究揭示[111In]In-hu3F8在肿瘤组织中的选择性摄取。自发性OS犬的SPECT/CT成像显示所有转移性病变中[111In]In-hu3F8的强烈摄取。免疫组织化学证实了放射性标记的hu3F8在骨和软病变中的广泛结合。
这项研究证明了使用基于hu3F8的放射性药物成像在OS细胞和自发性OS犬肿瘤上靶向GD2的可行性。它以有针对性的方式提供成像有效载荷的能力支持hu3F8用于OS的精确成像和放射性药物治疗的潜在未来用途。
Osteosarcoma (OS) is the most frequently diagnosed bone cancer in children with little improvement in overall survival in the past decades. The high surface expression of disialoganglioside GD2 on OS tumors and restricted expression in normal tissues makes it an ideal target for anti-OS radiopharmaceuticals. Since human and canine OS share many biological and molecular features, spontaneously occurring OS in canines has been an ideal model for testing new imaging and treatment modalities for human translation. In this study, we evaluated a humanized anti-GD2 antibody,
hu3F8, as a potential delivery vector for targeted radiopharmaceutical imaging of human and canine OS.
The cross-reactivity of hu3F8 with human and canine OS cells and tumors was examined by immunohistochemistry and flow cytometry. The
hu3F8 was radiolabeled with indium-111, and the biodistribution of [111In]In-
hu3F8 was assessed in tumor xenograft-bearing mice. The targeting ability of [111In]In-
hu3F8 to metastatic OS was tested in spontaneous OS canines.
The hu3F8 cross reacts with human and canine OS cells and canine OS tumors with high binding affinity. Biodistribution studies revealed selective uptake of [111In]In-
hu3F8 in tumor tissue. SPECT/CT imaging of spontaneous OS canines demonstrated avid uptake of [111In]In-hu3F8 in all metastatic lesions. Immunohistochemistry confirmed the extensive binding of radiolabeled
hu3F8 within both osseous and soft lesions.
This study demonstrates the feasibility of targeting GD2 on OS cells and spontaneous OS canine tumors using hu3F8-based radiopharmaceutical imaging. Its ability to deliver an imaging payload in a targeted manner supports the utility of hu3F8 for precision imaging of OS and potential future use in radiopharmaceutical therapy.