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


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.


CONCLUSIONS
(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.
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.
Laura K
LK
van Dijk
Bianca A W
BA
Hoeben
Hanneke
H
Stegeman
Johannes H A M
JH
Kaanders
Gerben M
GM
Franssen
Otto C
OC
Boerman
Johan
J
Bussink
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism*; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000032:analysis* / Q000037:antagonists & inhibitors; D006258:Head and Neck Neoplasms / Q000737:chemistry*; D064593:Heterografts; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D000077195:Squamous Cell Carcinoma of Head and Neck; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D066246:ErbB Receptors; D000068818:Cetuximab
Cetuximab; EGFR imaging; Head and neck cancer; Preclinical; SPECT