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

✍ Scribed by Bianca A.W. Hoeben; Janneke D.M. Molkenboer-Kuenen; Wim J.G. Oyen; Wenny J.M. Peeters; Johannes H.A.M. Kaanders; Johan Bussink; Otto C. Boerman

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 563 KB
• Volume: 129
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.25727

✦ Synopsis

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.