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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2009

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

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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 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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Metadata
Title
Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts
Authors
Kristin McLarty
Bart Cornelissen
Deborah A. Scollard
Susan J. Done
Kathy Chun
Raymond M. Reilly
Publication date
01-01-2009
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0923-x

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