Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model

The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this st...

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Published in:Oncotarget 2017-11, Vol.8 (54), p.92090-92105
Main Authors: Song, In Ho, Noh, Youn, Kwon, Junhye, Jung, Jae Ho, Lee, Byung Chul, Kim, Kwang Il, Lee, Yong Jin, Kang, Joo Hyun, Rhee, Chae Seo, Lee, Chul Hee, Lee, Tae Sup, Choi, Ik Joon
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Language:English
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Research Paper
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Summary:The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this study, we evaluated the feasibility of immuno-positron emission tomography (PET) imaging and radioimmunotherapy (RIT) with Cu-/ Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model. The cellular uptake of Cu/ Lu-3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA)-cetuximab showed good correlation with western blot and flow cytometry analysis in EGFR expression level of various HNSCC cells. Lu-PCTA-cetuximab selectively killed cetuximab-resistant SNU-1066 cells . Cu-/ Lu-PCTA-cetuximab specifically accumulated in SNU-1066 tumor and those uptakes were peaked at 48 h and 7 day, respectively in biodistribution, PET and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. RIT with single dose of Lu-PCTA-cetuximab exhibited significant tumor regression and markedly reduced 2-[ F]fluoro-2-deoxy-D-glucose ( F-FDG) uptake, compared to other groups. Proliferation index were dramatically decreased and apoptotic index increased in RIT group. These results suggest that a diagnostic and therapeutic convergence radiopharmaceutical, Cu-/ Lu-PCTA-cetuximab has the potential of target selection using immuno-PET imaging and targeted therapy by RIT in EGFR expressing cetuximab-resistant HNSCC tumors.
ISSN:1949-2553
DOI:10.18632/oncotarget.20760