Abstract | UNLABELLED: METHODS: Mice with HNSCC xenografts, cetuximab-sensitive SCCNij202 and cetuximab-resistant SCCNij167, were imaged with SPECT/CT using (111)In-cetuximab-F(ab')2 as a tracer, directly followed by PET imaging with (18)F-FDG. Scans were acquired 7 d before radiotherapy (10 Gy) and 1, 7, and 14 d after treatment. Intratumoral localization of (111)In-cetuximab-F(ab')(2) was evaluated by autoradiography and histologic markers evaluated by immunofluorescence staining in the same tumor sections. RESULTS: Growth of irradiated SCCNij202 and SCCNij167 tumors was significantly delayed, compared with controls (P < 0.05). No changes in uptake of (18)F-FDG were observed in either of the xenografts after radiotherapy. SPECT images of tumor-bearing mice showed a significant increase in uptake of (111)In-cetuximab-F(ab')(2) in the SCCNij202 tumors after irradiation ( tumor-to-liver ratio, 4.3 ± 1.1 vs. 10.5 ± 3.3, 7 d before and 14 d after treatment, respectively, P < 0.01) but not in SCCNij167 tumors. Immunohistochemical EGFR staining showed a translocation of the EGFR from the cytoplasm to the cell membrane in irradiated SCCNij202 xenografts. Intratumoral distribution of (111)In-cetuximab-F(ab')(2) as determined by autoradiography correlated well with the distribution of EGFR as determined immunohistochemically (r = 0.85; range, 0.69-0.95). CONCLUSION: EGFR accessibility can be visualized with (111)In-cetuximab-F(ab')(2). (111)In-cetuximab-F(ab')(2) uptake increased after irradiation only in cetuximab-sensitive SCCNij202 xenografts, implying that the tracer can be used to measure irradiation-induced changes of EGFR expression and can monitor the compensatory response of tumors to radiotherapy.
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Authors | Laura K van Dijk, Otto C Boerman, Gerben M Franssen, Jasper Lok, Johannes H A M Kaanders, Johan Bussink |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 55
Issue 10
Pg. 1665-70
(Oct 2014)
ISSN: 1535-5667 [Electronic] United States |
PMID | 25236350
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Immunoglobulin Fragments
- Fluorodeoxyglucose F18
- ErbB Receptors
- Cetuximab
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(therapeutic use)
- Carcinoma, Squamous Cell
(diagnostic imaging)
- Cell Line, Tumor
- Cetuximab
- Disease Models, Animal
- ErbB Receptors
(metabolism)
- Fluorodeoxyglucose F18
- Head and Neck Neoplasms
(diagnostic imaging)
- Humans
- Image Processing, Computer-Assisted
- Immunoglobulin Fragments
(chemistry)
- Immunohistochemistry
- Mice
- Mice, Inbred BALB C
- Multimodal Imaging
(methods)
- Neoplasm Transplantation
- Positron-Emission Tomography
(methods)
- Radiotherapy
(methods)
- Tomography, Emission-Computed, Single-Photon
(methods)
- Tomography, X-Ray Computed
(methods)
|