Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts
Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts
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DOI：
10.1007/s00259-008-0923-x
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发表时间：
2009-01-01
影响因子：
9.1
通讯作者：
Reilly, Raymond M.
中科院分区：
文献类型：
--
作者：
McLarty, Kristin;Cornelissen, Bart;Reilly, Raymond M.
目的-本研究的目的是调查在-111-DTPA-曲妥珠单抗的摄取，肿瘤HER 2密度和对曲妥珠单抗（赫赛汀）的人乳腺癌（BC）异种移植物在athymic mice.Materials和方法在-111-DTPA-曲妥珠单抗的肿瘤摄取在荷瘤裸鼠的BC异种移植物与增加HER 2密度（0至3+）之间的关联进行了评价。使用In-111标记的小鼠IgG（In-111-DTPA-mIgG）在生物分布（SUR）和成像研究（ROI-SUR）中确定了特异性摄取率。分别使用定义为定位指数（LI）和感兴趣区域定位指数（ROI-LI）的肿瘤-血液比值对循环放射性进行进一步校正。用曲妥珠单抗（赫赛汀）处理小鼠。计算肿瘤生长抑制指数（TGI），并通过将对照小鼠的TGI除以曲妥珠单抗治疗小鼠的TGI来计算相对TGI。SUR; r（2）=0.99）和循环放射性（即，LI; r（2）=0.87），但在没有这些校正的情况下，HER 2密度与肿瘤摄取之间的关联性较差（r（2）=0.22）。ROI-SUR和ROI-LI值与HER 2表达之间存在强相关性（分别为r（2）=0.90和r（2）=0.95）。对所有肿瘤进行成像。相对TGI值与In-111-DTPA-曲妥珠单抗的未校正肿瘤摄取增加相关，但不总是与HER 2密度相关（即，结论使用In-111-DTPA-曲妥珠单抗可以区分HER 2表达（0至3+），但需要校正肿瘤摄取的非特异性IgG定位和循环放射性。In-111-DTPA-曲妥珠单抗的未校正摄取与肿瘤对曲妥珠单抗的应答相关。
Purpose The purpose of the study was to investigate the associations between uptake of In-111-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 In-111-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 In-111-labeled mouse IgG (In-111-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 In-111-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 In-111-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 In-111-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of In-111-DTPA-trastuzumab was associated with tumour response to trastuzumab.