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

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.