Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model

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 x 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 mug 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.