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European Journal of Nuclear Medicine and Molecular Imaging

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01.01.2009 | Original Article

Associations between the uptake of ¹¹¹In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts

verfasst von: Kristin McLarty, Bart Cornelissen, Deborah A. Scollard, Susan J. Done, Kathy Chun, Raymond M. Reilly

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 1/2009

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Abstract

Purpose

The purpose of the study was to investigate the associations between uptake of ¹¹¹In-DTPA-trastuzumab, tumour HER2 density and response to trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice.

Materials and methods

The tumour uptake of ¹¹¹In-DTPA-trastuzumab in athymic mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated. Specific uptake ratios were established in biodistribution (SUR) and imaging studies (ROI-SUR) using ¹¹¹In-labeled mouse IgG (¹¹¹In-DTPA-mIgG). Further corrections were made for circulating radioactivity using tumour-to-blood ratios defined as a localization index (LI) and region-of-interest localization index (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour growth inhibition index (TGI) was calculated and relative TGIs calculated by dividing the TGI of control by that of trastuzumab-treated mice.

Results

Strong, nonlinear associations with HER2 density were obtained if the uptake of ¹¹¹In-DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r ² = 0.99) and circulating radioactivity (i.e., LI; r ² = 0.87), but without these corrections, the association between HER2 density and tumour uptake was poor (r ² = 0.22). There was a strong association between ROI-SUR and ROI-LI values and HER2 expression (r ² = 0.90 and r ² = 0.95, respectively. All tumours were imaged. Relative TGI values were associated with increasing uncorrected tumour uptake of ¹¹¹In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF-HER2-18 cells with trastuzumab-resistance).

Conclusion

HER2 expression (0 to 3+) can be differentiated using ¹¹¹In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of ¹¹¹In-DTPA-trastuzumab was associated with tumour response to trastuzumab.

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Titel: Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts
verfasst von: Kristin McLarty
Bart Cornelissen
Deborah A. Scollard
Susan J. Done
Kathy Chun
Raymond M. Reilly
Publikationsdatum: 01.01.2009
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 1/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-0923-x

Springer Medizin

Abstract

Purpose

Materials and methods

Results

Conclusion

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