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Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous
Bianca A W Hoeben1, Janneke D M Molkenboer-Kuenen, Wim J G Oyen
1Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.hoeben@rther.umcn.nl
Abstract:
Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous cell carcinoma could be of value to select patients for EGFR-targeted therapy. We assessed dose optimization of (111) Indium-DTPA-cetuximab ((111) In-cetuximab) for EGFR imaging in a head-and-neck squamous cell carcinoma xenograft model. (111) In-cetuximab slowly internalized into FaDu cells in vitro, amounting to 1.0 × 10(4) molecules cetuximab per cell after 24 hr (15.8% of added activity). In nude mice with subcutaneous FaDu xenograft tumors, a protein dose escalation study with (111) In-cetuximab showed highest specific accumulation in tumors at protein doses between 1 and 30 μg per mouse (mean tumor uptake 33.1 ± 3.1%ID/g, 3 days postinjection (p.i.)). The biodistribution of (111) In-cetuximab and (125) I-cetuximab was determined at 1, 3 and 7 days p.i. at optimal protein dose. Tumor uptake was favorable for (111) In-cetuximab compared to (125) I-cetuximab. With pixel-by-pixel analysis, good correlations were found between intratumoral distribution of (111) In-cetuximab as determined by autoradiography and EGFR expression in the same tumor sections as determined immunohistochemically (mean r = 0.74 ± 0.14; all correlations p < 0.0001). Micro Single Photon Emission Computed Tomography (MicroSPECT) scans clearly visualized FaDu tumors from 1 day p.i. onward and tumor-to-background contrast increased until 7 days p.i. (tumor-to-liver ratios 0.58 ± 0.24, 3.42 ± 0.66, 8.99 ± 4.66 and 16.33 ± 11.56, at day 0, day 1, day 3 and day 7 p.i., respectively). Our study suggests that, at optimal cetuximab imaging dose, (111) In-cetuximab can be used for visualization of EGFR expression in head-and-neck squamous cell carcinoma using SPECT.
Insights
This study optimized Indium-111-labeled cetuximab for imaging epidermal growth factor receptor (EGFR) in head-and-neck cancer. The optimized imaging agent successfully visualized EGFR expression in xenograft models using SPECT, aiding patient selection for targeted therapies.
Area of Science:
- Nuclear medicine
- Oncology
- Radiopharmaceutical development
Background:
- Noninvasive imaging of epidermal growth factor receptor (EGFR) is crucial for selecting patients for EGFR-targeted therapy in head-and-neck squamous cell carcinoma.
- Cetuximab is a monoclonal antibody targeting EGFR, but its utility in diagnostic imaging requires optimization.
Purpose of the Study:
- To optimize the protein dose of Indium-111-DTPA-cetuximab ((111) In-cetuximab) for noninvasive imaging of EGFR in a head-and-neck squamous cell carcinoma xenograft model.
- To evaluate the biodistribution and tumor uptake of (111) In-cetuximab using microSPECT imaging.
- To correlate the imaging results with EGFR expression levels determined by immunohistochemistry.
Main Methods:
- Dose escalation study of (111) In-cetuximab in nude mice bearing FaDu xenograft tumors.
- Biodistribution studies comparing (111) In-cetuximab and Iodine-125-cetuximab at various time points postinjection.
- Autoradiography and immunohistochemistry for correlating intratumoral tracer distribution with EGFR expression.
- Micro Single Photon Emission Computed Tomography (MicroSPECT) imaging to assess tumor visualization and contrast.
Main Results:
- Optimal tumor accumulation of (111) In-cetuximab was observed at protein doses between 1 and 30 μg per mouse, with high specific uptake.
- (111) In-cetuximab demonstrated favorable tumor uptake compared to (125) I-cetuximab.
- Strong correlation (mean r = 0.74) was found between intratumoral (111) In-cetuximab distribution and EGFR expression.
- MicroSPECT imaging clearly visualized tumors from 1 day postinjection, with increasing tumor-to-background contrast up to 7 days postinjection.
Conclusions:
- The optimized dose of (111) In-cetuximab allows for effective noninvasive visualization of EGFR expression in head-and-neck squamous cell carcinoma using SPECT.
- This imaging approach holds potential for patient selection for EGFR-targeted therapies.
