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We assessed dose optimization of <jats:sup>111<\/jats:sup>Indium\u2010DTPA\u2010cetuximab (<jats:sup>111<\/jats:sup>In\u2010cetuximab) for EGFR imaging in a head\u2010and\u2010neck squamous cell carcinoma xenograft model. <jats:sup>111<\/jats:sup>In\u2010cetuximab slowly internalized into FaDu cells <jats:italic>in vitro<\/jats:italic>, amounting to 1.0 \u00d7 10<jats:sup>4<\/jats:sup> 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 <jats:sup>111<\/jats:sup>In\u2010cetuximab showed highest specific accumulation in tumors at protein doses between 1 and 30 \u03bcg per mouse (mean tumor uptake 33.1 \u00b1 3.1%ID\/g, 3 days postinjection (p.i.)). The biodistribution of <jats:sup>111<\/jats:sup>In\u2010cetuximab and <jats:sup>125<\/jats:sup>I\u2010cetuximab was determined at 1, 3 and 7 days p.i. at optimal protein dose. Tumor uptake was favorable for <jats:sup>111<\/jats:sup>In\u2010cetuximab compared to <jats:sup>125<\/jats:sup>I\u2010cetuximab. With pixel\u2010by\u2010pixel analysis, good correlations were found between intratumoral distribution of <jats:sup>111<\/jats:sup>In\u2010cetuximab as determined by autoradiography and EGFR expression in the same tumor sections as determined immunohistochemically (mean <jats:italic>r<\/jats:italic> = 0.74 \u00b1 0.14; all correlations <jats:italic>p<\/jats:italic> &lt; 0.0001). Micro Single Photon Emission Computed Tomography (MicroSPECT) scans clearly visualized FaDu tumors from 1 day p.i. onward and tumor\u2010to\u2010background contrast increased until 7 days p.i. (tumor\u2010to\u2010liver ratios 0.58 \u00b1 0.24, 3.42 \u00b1 0.66, 8.99 \u00b1 4.66 and 16.33 \u00b1 11.56, at day 0, day 1, day 3 and day 7 p.i., respectively). Our study suggests that, at optimal cetuximab imaging dose, <jats:sup>111<\/jats:sup>In\u2010cetuximab can be used for visualization of EGFR expression in head\u2010and\u2010neck squamous cell carcinoma using SPECT.<\/jats:p>","DOI":"10.1002\/ijc.25727","type":"journal-article","created":{"date-parts":[[2010,10,18]],"date-time":"2010-10-18T14:18:26Z","timestamp":1287411506000},"page":"870-878","source":"Crossref","is-referenced-by-count":51,"title":["Radiolabeled cetuximab: Dose optimization for epidermal growth factor receptor imaging in a head\u2010and\u2010neck squamous cell carcinoma model"],"prefix":"10.1002","volume":"129","author":[{"given":"Bianca A.W.","family":"Hoeben","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janneke D.M.","family":"Molkenboer\u2010Kuenen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim 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