Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma

Abstract

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 ow cytometry. The hu3F8 was radiolabeled with Indium-111 and the biodistribution of [ 111 In]In-hu3F8 was assessed in tumor xenograft-bearing mice. The targeting ability of [ 111 In]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 a nity. Biodistribution studies revealed selective uptake of [ 111 In]In-hu3F8 in tumor tissue. SPECT/CT imaging of spontaneous OS canines demonstrated avid uptake of [ 111 In]In-hu3F8 in all metastatic lesions. Immunohistochemistry con rmed 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 suggests that labeling hu3F8 with a therapeutic radionuclide may yield a potent radiopharmaceutical agent against OS.

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic

“…These preclinical models serve as future study designs by combining targeted radionuclides with immune checkpoint inhibitors and external beam radiation therapy in human patients. In addition, the University of Missouri has started to test a humanized antibody against GD2 ganglioside coated with Ln111 using canine osteosarcoma cell lines with positive cross-linking [ 53 ].…”