期刊
RADIOTHERAPY AND ONCOLOGY
卷 110, 期 2, 页码 362-369出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2013.12.001
关键词
Radioimmunotherapy; Radiotherapy; Epidermal growth factor receptor (EGFR) inhibition; Combined treatment; Cetuximab
资金
- Kompetenzverbund Strahlenforschung [02NUK006A+B]
Purpose: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined. Methods: Growth delay was evaluated in three human squamous cell carcinoma models after RIT with [Y-90]-(CHX-A-DTPA)(4)-cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD50) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([Y-86]Y-(CHX-A-DTPA)(4)-cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab. Results: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD50 after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT. Conclusion: EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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