科研之友
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摘要
We previously reported that microSPECT/CT imaging with In-111-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')(2) of pertuzumab modified with NOTA chelators for complexing Cu-64. The effect of the administered mass (5-200 mu g) of Cu-64-NOTA-pertuzumab F(ab')(2) was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts. Biodistribution studies were performed in non-tumor bearing Balb/c mice to predict radiation doses to normal organs in humans. Serial PET/CT imaging was conducted on mice engrafted with HER2-positive and trastuzumab-sensitive BT-474 or trastuzumab-insensitive SK-OV-3 xenografted mice treated with weekly doses of trastuzumab. There were no significant effects of the administered mass of Cu-64-NOTA-pertuzumab F(ab')(2) on tumor or normal tissue uptake. The predicted total body dose in humans was 0.015 mSv/MBq, a 3.3-fold reduction compared to In-111-labeled pertuzumab. MicroPET/CT images revealed specific tumor uptake of Cu-64-NOTA-pertuzumab F(ab')(2) at 24 or 48 h post-injection in mice with SK-OV-3 tumors. Image analysis of mice treated with trastuzumab showed 2-fold reduced uptake of Cu-64-NOTA-pertuzumab F(ab')(2) in BT-474 tumors after 1 week of trastuzumab normalized to baseline, and 1.9-fold increased uptake in SK-OV-3 tumors after 3 weeks of trastuzumab, consistent with tumor response and resistance, respectively. We conclude that PET/CT imaging with Cu-64-NOTA-pertuzumab F(ab')(2) detected changes in HER2 expression in response to trastuzumab while delivering a lower total body radiation dose compared to In-111-labeled pertuzumab.
- 出版日期2017
