111In-cetuximab-F(ab')2 SPECT imaging for quantification of accessible epidermal growth factor receptors (EGFR) in HNSCC xenografts.

Autor: van Dijk LK; Department of Radiation Oncology, Radboud University Nijmegen Medical Center, The Netherlands; Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, The Netherlands. Electronic address: l.vandijk@rther.umcn.nl., Hoeben BA, Stegeman H, Kaanders JH, Franssen GM, Boerman OC, Bussink J
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2013 Sep; Vol. 108 (3), pp. 484-8. Date of Electronic Publication: 2013 Aug 07.
DOI: 10.1016/j.radonc.2013.06.034
Abstrakt: Background and Purpose: Immunohistochemical epidermal growth factor receptor (EGFR) expression does not correlate with treatment response in head and neck squamous cell carcinomas (HNSCC). Aim was to apply the tracer (111)In-cetuximab-F(ab')2 for EGFR microSPECT imaging and to investigate if tracer uptake correlated with response to EGFR-inhibition by cetuximab in HNSCC xenografts. Usage of F(ab)2 fragments allows for shorter interval between tracer injection and imaging.
Materials and Methods: Mice with HNSCC xenografts, SCCNij202, 153, 185 and 167 were imaged with microSPECT using (111)In-cetuximab-F(ab')2. Subsequently, tumors were analyzed by autoradiography and immunohistochemistry and tracer concentration was determined. Tumor uptake was correlated with previously assessed response to cetuximab treatment.
Results: MicroSPECT imaging showed preferential uptake in HNSCC xenografts. Tumor-to-liver ratios were 3.1 ± 0.2 (SCCNij202), 2.8 ± 0.4 (SCCNij153), 2.0 ± 0.8 (SCCNij185), 2.0 ± 0.4 (SCCNij167). Immunohistochemical EGFR fractions (fEGFR) differed significantly between xenografts; 0.77 ± 0.07 (SCCNij202), 0.66 ± 0.11 (SCCNij153), 0.57 ± 0.19 (SCCNij185), 0.16 ± 0.10 (SCCNij167) (p < 0.001). Tumor fEGFR correlated with (111)In-cetuximab-F(ab')2 tumor uptake (r = 0.6, p < 0.01) and tracer autoradiography (r = 0.7, p < 0.0001). Tumor uptake of (111)In-cetuximab-F(ab')2 was proportionally associated with cetuximab treatment response in three out of four xenograft models.
Conclusion: (111)In-cetuximab-F(ab')2 showed good tumor-to-background contrast on microSPECT imaging, allowing noninvasive assessment of EGFR expression in vivo, and possibly evaluation of treatment response to EGFR-inhibition.
(Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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