Radiolabeled cetuximab: dose optimization for epidermal growth factor receptor imaging in a head-and-neck squamous cell carcinoma model.
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.
Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.hoeben@rther.umcn.nl
Bianca A W
BA
Hoeben
Janneke D M
JD
Molkenboer-Kuenen
Wim J G
WJ
Oyen
Wenny J M
WJ
Peeters
Johannes H A M
JH
Kaanders
Johan
J
Bussink
Otto C
OC
Boerman
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D004369:Pentetic Acid / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; D004369:Pentetic Acid; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab