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Radiolabeled cetuximab: Dose optimization for epidermal growth factor receptor imaging in a head‐and‐neck squamous cell carcinoma model
Author(s) -
Hoeben Bianca A.W.,
MolkenboerKuenen Janneke D.M.,
Oyen Wim J.G.,
Peeters Wenny J.M.,
Kaanders Johannes H.A.M.,
Bussink Johan,
Boerman Otto C.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25727
Subject(s) - cetuximab , epidermal growth factor receptor , head and neck squamous cell carcinoma , medicine , pathology , cancer research , head and neck cancer , nuclear medicine , radiation therapy , cancer , colorectal cancer
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.