Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models
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Updated: Oct 29, 2025
The Bioconjugation and Radiosynthesis of 89Zr-DFO-labeled Antibodies
Published on: February 12, 2015
Vasilios Liapis1, William Tieu2,3, Nicole L Wittwer4
1Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Level 9 University of South Australia Health Innovation Building, North Terrace, Adelaide, 5000, Australia. vasilios.liapis@sa.gov.au.
Purpose:
Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment. Therefore, chDAB4 is a unique diagnostic tool that detects dead cancer cells and thus could distinguish between treatment responsive and nonresponsive patients.
Procedures:
In clinically relevant tumor models, mice bearing subcutaneous xenografts of human ovarian or lung cancer cell lines or intraperitoneal ovarian cancer xenografts were untreated or given chemotherapy followed 24h later by chDAB4 radiolabeled with [89Zr]ZrIV. Tumor responses were monitored using bioluminescence imaging and caliper measurements. [89Zr]Zr-chDAB4 uptake in tumor and normal tissues was measured using an Albira SI Positron-Emission Tomography (PET) imager and its biodistribution was measured using a Hidex gamma-counter.
Results:
Tumor uptake of [89Zr]Zr-chDAB4 was detected in untreated mice, and uptake significantly increased in both human lung and ovarian tumors after chemotherapy, but not in normal tissues.
Conclusion:
Given that tumors, rather than normal tissues, were targeted after chemotherapy, these results support the clinical development of chDAB4 as a radiodiagnostic imaging agent and as a potential predictive marker of treatment response.
Insights
The novel antibody chDAB4 (APOMAB®) shows promise for early cancer treatment response detection. It selectively targets dying cancer cells, aiding in distinguishing responsive from nonresponsive tumors noninvasively.
Area of Science:
- Oncology
- Radiochemistry
- Immunology
Background:
- Early detection of tumor treatment response is crucial but lacks noninvasive methods.
- The Lupus-associated antigen (La/SSB) is over-expressed in malignancies.
- chDAB4 (APOMAB®) is an antibody targeting La/SSB, selectively binding to cancer cells undergoing DNA-damage-induced death.
Purpose of the Study:
- To evaluate chDAB4 as a diagnostic tool for detecting tumor treatment response.
- To assess the potential of chDAB4 as a noninvasive method for distinguishing treatment-responsive from nonresponsive patients.
- To explore chDAB4's role as a predictive marker for chemotherapy efficacy.
Main Methods:
- Radiolabeling chDAB4 with [89Zr]ZrIV for PET imaging.
- Administering [89Zr]Zr-chDAB4 to mice with human ovarian and lung cancer xenografts post-chemotherapy.
- Monitoring tumor response using bioluminescence imaging, caliper measurements, and PET imaging.
Main Results:
- [89Zr]Zr-chDAB4 demonstrated uptake in tumors of untreated mice.
- Significant increase in [89Zr]Zr-chDAB4 uptake was observed in both lung and ovarian tumors after chemotherapy.
- No significant uptake was detected in normal tissues, indicating tumor selectivity.
Conclusions:
- chDAB4 selectively targets tumors, especially after chemotherapy.
- These findings support the clinical development of chDAB4 as a radiodiagnostic imaging agent.
- chDAB4 shows potential as a predictive marker for cancer treatment response.
