Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts.
PURPOSE: The purpose of the study was to investigate the associations between uptake of (111)In-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 (111)In-DTPA-trastuzumab...
| Glavni autori: | , , , , , |
|---|---|
| Format: | Journal article |
| Jezik: | English |
| Izdano: |
2009
|
| _version_ | 1826306307615883264 |
|---|---|
| author | McLarty, K Cornelissen, B Scollard, D Done, S Chun, K Reilly, R |
| author_facet | McLarty, K Cornelissen, B Scollard, D Done, S Chun, K Reilly, R |
| author_sort | McLarty, K |
| collection | OXFORD |
| description | PURPOSE: The purpose of the study was to investigate the associations between uptake of (111)In-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 (111)In-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 (111)In-labeled mouse IgG ((111)In-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 (111)In-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 (111)In-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 (111)In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of (111)In-DTPA-trastuzumab was associated with tumour response to trastuzumab. |
| first_indexed | 2024-03-07T06:45:58Z |
| format | Journal article |
| id | oxford-uuid:fadd97fc-816e-4dd7-a181-4d56fdf2626d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:45:58Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:fadd97fc-816e-4dd7-a181-4d56fdf2626d2022-03-27T13:09:27ZAssociations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fadd97fc-816e-4dd7-a181-4d56fdf2626dEnglishSymplectic Elements at Oxford2009McLarty, KCornelissen, BScollard, DDone, SChun, KReilly, R PURPOSE: The purpose of the study was to investigate the associations between uptake of (111)In-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 (111)In-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 (111)In-labeled mouse IgG ((111)In-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 (111)In-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 (111)In-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 (111)In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of (111)In-DTPA-trastuzumab was associated with tumour response to trastuzumab. |
| spellingShingle | McLarty, K Cornelissen, B Scollard, D Done, S Chun, K Reilly, R Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title | Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title_full | Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title_fullStr | Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title_full_unstemmed | Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title_short | Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. |
| title_sort | associations between the uptake of 111in dtpa trastuzumab her2 density and response to trastuzumab herceptin in athymic mice bearing subcutaneous human tumour xenografts |
| work_keys_str_mv | AT mclartyk associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts AT cornelissenb associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts AT scollardd associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts AT dones associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts AT chunk associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts AT reillyr associationsbetweentheuptakeof111indtpatrastuzumabher2densityandresponsetotrastuzumabherceptininathymicmicebearingsubcutaneoushumantumourxenografts |