Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model
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In Ho Song1,*, Youn Noh2,*, Junhye Kwon2, Jae Ho Jung3, Byung Chul Lee3, Kwang Il Kim1, Yong Jin Lee1, Joo Hyun Kang1, Chae Seo Rhee4, Chul Hee Lee4, Tae Sup Lee1 and Ik Joon Choi2,5
1Division of RI Convergence Research, Research Institute of Radiological and Medical Sciences (RIRAMS), Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea
2Division of Radiological and Clinical Research, Korea Cancer Center Hospital (KCCH), Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea
3Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
4Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
5Department of Otorhinolaryngology-Head and Neck Surgery, Korea Cancer Center Hospital (KCCH), Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, Republic of Korea
*These authors have contributed equally to this work
Tae Sup Lee, email: [email protected]
Ik Joon Choi, email: [email protected]
Keywords: immuno-PET, radioimmunotherapy, cetuximab, EGFR, head and neck squamous cell carcinoma
Received: June 16, 2017 Accepted: August 04, 2017 Published: September 08, 2017
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.
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