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Published on: January 22, 2018
Pilot study of HER2 targeted 64 Cu-DOTA-tagged PET imaging in gastric cancer patients
Matthew C Hernandez1, Paul Yazaki2, Joanne E Mortimer3
1Division of Surgical Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center, .
Objective:
Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64 Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64 Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients.
Methods:
We conducted a single-arm phase II pilot study exploring the feasibility of 64 Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45 mg of cold trastuzumab followed by 5 mg of 64 Cu-DOTA-trastuzumab. PET-CT scans were performed 24-48 h post radiotracer injection and compared to standard staging CT scans.
Results:
We observed limited toxicity following 64 Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis.
Conclusion:
Despite the potential of 64 Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5 mg dose of this radiotracer injected 24-48 h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.
Insights
This study found that 64 Cu-DOTA-trastuzumab PET-CT imaging was insufficient for detecting HER2+ gastric cancer (GC) at the tested dosage. Future research should optimize radiotracer dosage and timing for effective HER2-targeted GC imaging.
Area of Science:
- Oncology
- Radiochemistry
- Medical Imaging
Background:
- Human epidermal growth factor receptor 2 (HER2) is a key biomarker for targeted gastric cancer (GC) immunotherapy.
- Heterogeneous HER2 expression and loss of expression during therapy present challenges for effective treatment.
- Non-invasive imaging methods are needed to identify HER2-positive tumors for targeted therapies.
Purpose of the Study:
- To develop and assess 64 Cu-DOTA-trastuzumab PET-CT for detecting and characterizing HER2 expression in GC patients.
- To evaluate the feasibility of using this radiotracer for imaging HER2-overexpressing GC compared to HER2-negative tumors.
Main Methods:
- A single-arm phase II pilot study involving eight patients with biopsy-confirmed gastric adenocarcinoma.
- Immunohistochemistry to assess HER2 overexpression in primary tumor biopsies.
- Administration of cold trastuzumab followed by 64 Cu-DOTA-trastuzumab, with PET-CT scans performed 24-48 hours post-injection.
Main Results:
- Limited toxicity was observed with 64 Cu-DOTA-trastuzumab injections.
- While some uptake in HER2-positive lesions was noted, standardized uptake value analysis did not show a statistically significant distinction between tumor and background.
- The tested 5 mg dose of 64 Cu-DOTA-trastuzumab was insufficient for identifying HER2+ GC.
Conclusions:
- Despite its utility in breast cancer, 64 Cu-DOTA-trastuzumab PET imaging at the tested dose and timing was inadequate for HER2+ GC detection.
- Findings suggest the need to optimize radiotracer dosage and imaging timing for future GC imaging studies.
- This research informs the development of more effective biomarker-targeted therapies for gastric cancer.
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