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


ABSTRACT: 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 64Cu-/177Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model. The cellular uptake of 64Cu/177Lu-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. 177Lu-PCTA-cetuximab selectively killed cetuximab-resistant SNU-1066 cells in vitro. 64Cu-/177Lu-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 177Lu-PCTA-cetuximab exhibited significant tumor regression and markedly reduced 2-[18F]fluoro-2-deoxy-D-glucose (18F-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, 64Cu-/177Lu-PCTA-cetuximab has the potential of target selection using immuno-PET imaging and targeted therapy by RIT in EGFR expressing cetuximab-resistant HNSCC tumors.

SUBMITTER: Song IH 

PROVIDER: S-EPMC5696166 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Song In Ho IH   Noh Youn Y   Kwon Junhye J   Jung Jae Ho JH   Lee Byung Chul BC   Kim Kwang Il KI   Lee Yong Jin YJ   Kang Joo Hyun JH   Rhee Chae Seo CS   Lee Chul Hee CH   Lee Tae Sup TS   Choi Ik Joon IJ  

Oncotarget 20170908 54


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 <sup>64</sup>Cu-/<sup>177</sup>Lu-PCTA-cetuximab in cetuximab-resistant SNU-106  ...[more]

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