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Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma
Yingli Fu1, Jing Yu1, Ioanna Liatsou1
1Department of Radiology and Radiological Science, the Johns Hopkins University School of Medicine, MD, Baltimore, USA.
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.
Insights
A humanized anti-GD2 antibody, hu3F8, effectively targets osteosarcoma (OS) in canine models. This antibody shows promise for precision imaging and potential radiopharmaceutical therapy of OS in humans.
Area of Science:
- Oncology
- Immunology
- Radiopharmaceutical Science
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in children with stagnant survival rates.
- Disialoganglioside GD2 is highly expressed on OS tumors, making it a prime target for diagnostic and therapeutic agents.
- Canine OS models offer valuable insights for human OS treatment due to shared biological characteristics.
Purpose of the Study:
- To evaluate the humanized anti-GD2 antibody, hu3F8, as a delivery vector for targeted radiopharmaceutical imaging of human and canine OS.
- To assess the cross-reactivity and targeting capability of hu3F8 in both human and canine OS models.
Main Methods:
- Immunohistochemistry and flow cytometry were used to examine hu3F8 cross-reactivity with OS cells and tumors.
- hu3F8 was radiolabeled with indium-111 ([111In]In-hu3F8) for biodistribution studies in mice.
- Targeting of metastatic OS was evaluated in spontaneous canine OS models using SPECT/CT imaging.
Main Results:
- hu3F8 demonstrated high binding affinity to human and canine OS cells and tumors.
- [111In]In-hu3F8 exhibited selective uptake in tumor tissues.
- SPECT/CT imaging revealed significant uptake in all metastatic lesions in canines, confirmed by immunohistochemistry.
Conclusions:
- hu3F8-based radiopharmaceutical imaging is feasible for targeting GD2 on OS cells and spontaneous canine tumors.
- The study supports hu3F8's utility for precise OS imaging.
- Results suggest potential future applications of hu3F8 in OS radiopharmaceutical therapy.
