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Updated: Jun 2, 2026
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The Bioconjugation and Radiosynthesis of 89Zr-DFO-labeled Antibodies
Published on: February 12, 2015
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Exploring the 89Zr/177Lu Theranostic Pairing with an Extracellular Matrix-Targeted Radiopharmaceutical against
Justin Hachey1,2, Tara D Viray1, Sebastian E Carrasco3
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Summary
This study developed a theranostic approach using radiolabeled antibodies targeting extra domain A of fibronectin (EDA-FN) for triple negative breast cancer (TNBC). The treatment significantly improved survival in mouse models with manageable toxicity.
Area of Science:
- Oncology
- Radiochemistry
- Immunotherapy
Background:
- Triple negative breast cancer (TNBC) is an aggressive malignancy with poor prognoses.
- Extra domain A of fibronectin (EDA-FN) is highly expressed in TNBC stroma, making it a potential therapeutic target.
- Theranostic approaches offer personalized treatment by combining diagnostic imaging and targeted therapy.
Purpose of the Study:
- To synthesize and characterize novel theranostic radiopharmaceuticals targeting EDA-FN for TNBC.
- To evaluate the efficacy and toxicity of these agents in preclinical TNBC models.
- To establish optimal dosimetry for therapeutic benefit.
Main Methods:
- Synthesis and in vitro/in vivo characterization of [89Zr]Zr-DFO-F8 and [177Lu]Lu-CHX-A''-DTPA-F8.
- Biodistribution studies and dosimetry estimation in TNBC xenograft mouse models.
- Therapeutic efficacy and toxicity assessment of [177Lu]Lu-CHX-A''-DTPA-F8.
Main Results:
- Both radiolabeled antibodies demonstrated similar in vitro characteristics and tumor accumulation.
- [177Lu]Lu-CHX-A''-DTPA-F8 significantly prolonged survival in TNBC xenograft models.
- Transient myelosuppression was observed, with dose-dependent off-target myelotoxicity in specific mouse models.
Conclusions:
- The 89Zr/177Lu theranostic nuclide pairing successfully identified and treated TNBC xenografts.
- This approach shows promise for improving survival in triple negative breast cancer.
- Further investigation into targeted radiopharmaceuticals for TNBC is warranted.
