In vitro cytotoxicity of 211At-labeled trastuzumab in human breast cancer cell lines: effect of specific activity and HER2 receptor heterogeneity on survival fraction

Nuclear Medicine and Biology
G AkabaniM R Zalutsky

Abstract

Radioimmunotherapy with anti-HER2 monoclonal antibodies (mAbs) such as trastuzumab is a promising strategy for treating HER2-positive breast and ovarian carcinoma patients. The objective of this study was to determine the cytotoxic effectiveness of trastuzumab labeled with the 7.2-h half-life alpha-particle emitter 211At. Experiments were performed on SKBr-3, BT-474 and the transfected MCF7/HER2-18 human breast carcinoma cell lines. Intrinsic radiosensitivity was determined after exposure to external beam irradiation. The cytotoxicity of 211At-labeled trastuzumab was measured by clonogenic assays. The distribution of HER2 receptor expression on the cell lines was measured using fluorescence-activated cell sorting. A pharmacokinetic (PK)/microdosimetric model was established to assess the effects of specific activity (SA), HER2 receptor expression and absorbed dose on survival fraction (SF). With external beam irradiation, the 2-Gy SF for BT-474, SKBr-3 and MCF7/HER2-18 cells was 0.78, 0.53 and 0.64 Gy, respectively. Heterogeneous HER2 expression was observed, with a subpopulation of cells lacking measurable receptor (14.5%, SKBr-3; 0.34%, MCF-7/HER2; 1.73%, BT-474). When plotted as a function of activity concentration, SF curve...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Sep 1, 1993·Cancer Immunology, Immunotherapy : CII·G D LewisH M Shepard
Feb 13, 1999·International Journal of Cancer. Journal International Du Cancer·S BraunK Pantel
Jan 12, 2000·Archives of Disease in Childhood·D Hall
May 16, 2001·Radiation Research·C Mothersill, C Seymour
Feb 28, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N NormannoS Menard
Apr 30, 2002·Gan to kagaku ryoho. Cancer & chemotherapy·Yutaka TokudaTomoo Tajima
Sep 5, 2003·Cancer Biotherapy & Radiopharmaceuticals·Michael J BlendMartin W Brechbiel
Sep 26, 2003·Biophysical Journal·Bart S HendriksDouglas Lauffenburger
Jul 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ase M BallangrudGeorge Sgouros

Citations

Oct 20, 2009·Targeted Oncology·Gairin DanceyTim Meyer
Sep 6, 2008·Cancer Biotherapy & Radiopharmaceuticals·Jacques BarbetJean-François Chatal
Oct 19, 2012·Cancer Biotherapy & Radiopharmaceuticals·François GuérardMartin W Brechbiel
May 13, 2014·Immunotherapy·Christof Seidl
Aug 30, 2008·International Journal of Radiation Oncology, Biology, Physics·Andrey A RosenkranzAlexander S Sobolev
Sep 18, 2007·International Journal of Radiation Oncology, Biology, Physics·Stig PalmLars Jacobsson
Oct 9, 2007·Nuclear Medicine and Biology·M R ZalutskyDarell D Bigner
Dec 7, 2006·Neuroimaging Clinics of North America·Dawid Schellingerhout, Juri Gelovani
Sep 9, 2016·Biomacromolecules·Flonja LikoEduardo Fernandez-Megia
Mar 22, 2018·International Journal of Molecular Sciences·Benjamin B KastenDonald J Buchsbaum
Jan 19, 2018·Annual Review of Biomedical Engineering·Michael R McDevittStavroula Sofou
May 14, 2014·Physics in Medicine and Biology·Gyehong KimByungil Kim
Jan 11, 2013·Cancer Control : Journal of the Moffitt Cancer Center·Michael B TomblynPaul E Wallner
Nov 22, 2020·Nature Chemistry·Hua Wang, David J Mooney
Jul 29, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthias D'HuyvetterNick Devoogdt

Related Concepts

Herceptin
Monoclonal Antibodies
Astatine
Mammary Neoplasms, Human
Cell Survival
Colony-Forming Units Assay
Tumor Cells, Cultured
ErbB-2 Receptor
Radioimmunoconjugates
Antibodies, Monoclonal, Humanized