Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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用于骨肉瘤放射性药物显像的抗 GD2 抗体

目的

骨肉瘤 (OS) 是儿童中最常被诊断出的骨癌，在过去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有限表达使其成为抗 OS 放射性药物的理想靶点。由于人类和犬类 OS 具有许多生物学和分子特征，因此犬科动物中自发发生的 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，我们评估了一种人源化抗 GD2 抗体 hu3F8，作为人类和犬 OS 靶向放射性药物成像的潜在递送载体。

方法

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 进行放射性标记，并在荷瘤异种移植小鼠中评估[ ^{111 In]In-hu3F8 的生物分布。}在自发性 OS 犬中测试了 [ ¹¹¹ In]In-hu3F8 对转移性 OS的靶向能力。

结果

hu3F8 以高结合亲和力与人和犬 OS 细胞和犬 OS 肿瘤发生交叉反应。生物分布研究揭示了 [ ¹¹¹ In]In-hu3F8 在肿瘤组织中的选择性摄取。自发 OS 犬的 SPECT/CT 成像显示在所有转移性病灶中 [ ¹¹¹ In] In-hu3F8 的大量摄取。免疫组织化学证实了放射性标记的 hu3F8 在骨质和软质病变中的广泛结合。

结论

该研究证明了使用基于 hu3F8 的放射性药物成像将 GD2 靶向 OS 细胞和自发 OS 犬肿瘤的可行性。它以有针对性的方式提供成像有效载荷的能力支持 hu3F8 在 OS 精确成像和放射性药物治疗中的潜在未来用途。