Related Experiment Video
Updated: Jul 4, 2026
Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging
K A Kurdziel1, E Mena1, Y McKinney1
1Molecular Imaging Program (MIP), Center for Cancer Research (CCR)/National Cancer Institute (NCI), National Institutes of Health (NIH), USA.
Introduction:
Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status.
Methods:
111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions.
Results:
No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h).
Conclusion:
111In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.
Insights
This study shows that 111In-CHX-A"-DTPA trastuzumab is safe for imaging human patients. The imaging agent accurately identified HER2 expression in most patients, offering a potential non-invasive method for HER2 status determination.
Area of Science:
- Oncology
- Radiopharmaceuticals
- Molecular Imaging
Background:
- HER2-overexpressing tumors are linked to poorer prognosis.
- Accurate HER2 identification is crucial for effective targeted therapy selection.
- Trastuzumab and other HER2-targeted therapies improve survival in HER2(+) patients.
Purpose of the Study:
- To evaluate the safety and biodistribution of 111In-CHX-A"-DTPA trastuzumab.
- To assess the agent's ability to non-invasively determine HER2 status.
- To obtain preliminary data from a Phase 0 study in patients with known HER2 status.
Main Methods:
- 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site.
- 11 patients with known HER2 status received slow infusions.
- Single or multiple SPECT and/or gamma-camera imaging sessions were performed.
Main Results:
- The imaging agent was found to be safe with no identified issues.
- Imaging results correlated with tissue HER2 expression in 10 out of 11 patients.
- Biodistribution showed peak liver activity followed by gastrointestinal tract activity; clearance was characterized.
Conclusions:
- 111In-CHX-A"-DTPA trastuzumab is safe for human imaging.
- SPECT imaging with this agent shows concordance with tissue HER2 profiling.
- On-site radiolabeling and readily available components suggest an economical, non-invasive method for detecting HER2 overexpression.
