CC BY-NC-ND 4.0 · Laryngorhinootologie 2020; 99(S 02): S155
DOI: 10.1055/s-0040-1710998
Abstracts
Oncology

In-vitro targeted alpha-particle therapy (TAT) with 213Bi-Cetuximab outperforms X-Ray irradiation independent of HPV status of HNSCC cell lines

M Siegl
1   Technische Universität München, Department of Otolaryngology Head and Neck Surgery München
,
C Seidl
2   Technische Universität München, Department of Nuclear Medicine München
,
F Bruchertseifer
3   European Commission, JRC, Directorate for Nuclear Safety and Security Karlsruhe
,
A Morgenstern
3   European Commission, JRC, Directorate for Nuclear Safety and Security Karlsruhe
,
U Zissler
4   Technische Universität München und Helmholtz Zentrum München, Center of Allergy & Environment (ZAUM) München
,
G Multhoff
5   Technische Universität München, Center for Translational Cancer Research (TranslaTUM) München
,
B Wollenberg
1   Technische Universität München, Department of Otolaryngology Head and Neck Surgery München
,
A Pickhard
1   Technische Universität München, Department of Otolaryngology Head and Neck Surgery München
› Author Affiliations
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Introduction Radio resistance is a common issue in treatment of HNSCC. Infection with HPV increases radio sensitivity and survival, but for HPV negative tumors, alternative powerful treatment options are needed. Therefore, we compared the response of HNSCC cell lines for X-Ray and targeted alpha-particle therapy (TAT) with 213Bi-Cetuximab.

Materials & Methods We analyzed proliferation, cell cycle and yH2AX-intensity (flow cytometry) in six HNSCC cell lines (3 HPV(+)/3 HPV(-)) after treatment with 213Bi-Cetuximab and X-Rays. For two cell lines we quantified changes in overall gene expression (SurePrint G3 Human Gene Expression 8x60K Microarray).

Conclusions The impact of TAT on proliferation was more powerful than with X-Rays. In both treatments there were significant HPV-dependent differences in response, but with 213Bi-Cetuximab the radio resistance of HPV(-) group, that was seen with X-Rays, was diminished. With TAT all cell lines accumulated in the G2-Phase. With X-Ray this could be seen in the HPV(+) group only. TAT resulted in a delayed, stronger and more persistent peak level of yH2AX compared to X-Ray. Significant differences between the HPV-Groups were only true for X-Rays. Furthermore, in two analyzed cell lines, 213Bi-Cetuximab had a 3-4 fold stronger impact on changes in overall gene expression than X-Rays.

Conclusion Targeted alpha-particle therapy had a superior impact on the HNSCC cell lines, both in HPV positive and in more X-Ray resistant HPV negative cell lines. Our Results suggests the accumulation of cells in G2-phase to be responsible for this observation. The changes in gene expression remains to be examined in more detail, but treatment of HNSCC with 213Bi-Cetuximab seems like a promising approach and should be considered for clinical trials.

Poster-PDF A-1077.pdf



Publication History

Article published online:
10 June 2020

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