111In-cetuximab-F(ab')2 SPECT and 18F-FDG PET for prediction and response monitoring of combined-modality treatment of human head and neck carcinomas in a mouse model

J Nucl Med. 2015 Feb;56(2):287-92. doi: 10.2967/jnumed.114.148296. Epub 2014 Dec 31.


Treatment of head and neck squamous cell carcinomas with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor cetuximab shows an improved response in a subgroup of patients. The aim of this study was to noninvasively monitor treatment response by visualizing systemically accessible EGFR with (111)In-cetuximab-F(ab')2 while simultaneously evaluating tumor metabolism with (18)F-FDG PET during combined-modality treatment.

Methods: Eighty mice with patient-derived head and neck squamous cell carcinomas xenografts, SCCNij202 or SCCNij185, were imaged with SPECT/CT using (111)In-cetuximab-F(ab')2 (5 μg, 28 ± 6.1 MBq, 24 h after injection), followed by PET imaging with (18)F-FDG (9.4 ± 2.9 MBq, 1 h after injection). Scans were acquired on mice 10 d before treatment with either single-dose irradiation (10 Gy), cetuximab alone, or cetuximab-plus-irradiation combined or on untreated control mice. Scans were repeated 18 d after treatment. Tumor growth was monitored up to 120 d after treatment. EGFR expression was evaluated immunohistochemically.

Results: SCCNij202 responded to combined treatment (P < 0.01) and cetuximab treatment alone (P < 0.05) but not to irradiation alone (P = 0.13). SCCNij185 responded to combined treatment (P < 0.05) and irradiation (P < 0.05) but not to cetuximab treatment alone (P = 0.34). (111)In-cetuximab-F(ab')2 uptake (tumor-to-liver ratio, scan 2 - scan 1) predicted response to therapy. A positive response to treatment significantly correlated with a reduced tracer uptake in the tumor in the second SPECT scan, compared with the first scan (P < 0.005 and <0.05 for SCCNij202 and SCCNij185, respectively). Resistance to therapy was characterized by a significantly increased (111)In-cetuximab-F(ab')2 tumor uptake; tumor-to-liver ratio was 2.2 ± 0.6 to 3.5 ± 1.2, P < 0.01, for (irradiated) SCCNij202 and 1.4 ± 0.4 to 2.0 ± 0.3, P < 0.05, for (cetuximab-treated) SCCNij185, respectively. (18)F-FDG PET tumor uptake (maximum standardized uptake value, scan 2 - scan 1) correlated with tumor response for SCCNij202 (P < 0.01) but not for SCCNij185 (P = 0.66). EGFR fractions were significantly different: 0.9 ± 0.1 (SCCNij202) and 0.5 ± 0.1 (SCCNij185) (P < 0.001). The EGFR fraction was significantly lower for irradiated SCCNij202 tumors than for controls (P < 0.005).

Conclusion: (111)In-cetuximab-F(ab')2 predicted and monitored the effects of EGFR inhibition or irradiation during treatment in both head and neck carcinoma models investigated, whereas (18)F-FDG PET only correlated with tumor response in the SCCNij202 model. Thus, the additional value of the (111)In-cetuximab-F(ab')2 tracer is emphasized and the tracer can aid in evaluating future treatments with EGFR-targeted therapies.

Keywords: HNSCC; PET; SPECT; cetuximab; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized*
  • Biomarkers, Tumor / metabolism
  • Cetuximab
  • Combined Modality Therapy
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Fluorodeoxyglucose F18
  • Humans
  • Image Processing, Computer-Assisted
  • Immunoglobulin Fragments / chemistry*
  • Immunohistochemistry
  • Indium Radioisotopes*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography*
  • Tomography, Emission-Computed, Single-Photon*
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Immunoglobulin Fragments
  • Indium Radioisotopes
  • Fluorodeoxyglucose F18
  • ErbB Receptors
  • Cetuximab