Niu Gang, Cai Weibo, Chen Kai, Chen Xiaoyuan
The Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA.
Mol Imaging Biol. 2008 Mar-Apr;10(2):99-106. doi: 10.1007/s11307-007-0123-2. Epub 2007 Dec 22.
The aim of this study is to non-invasively monitor the epidermal growth factor receptor (EGFR) response to a Hsp90 inhibitor-17-AAG treatment in a PC-3 prostate cancer model.
Nude mice bearing PC-3 tumor were injected intraperitoneally with 17-AAG and then imaged with micro positron emission tomography (microPET) using (64)Cu-DOTA-cetuximab. Biodistribution studies, immunofluorescence staining, and Western blot were performed to validate the microPET results.
PC-3 cells are sensitive to 17-AAG treatment in a dose-dependent manner. Quantitative microPET showed that (64)Cu-DOTA-cetuximab has prominent tumor activity accumulation in untreated tumors (14.6 +/- 2.6%ID/g) but significantly lower uptake in 17-AAG-treated tumors (8.9 +/- 1.6% ID/g) at 24 h post-injection. Both immunofluorescence staining and Western blot confirmed the significantly lower EGFR expression level in the tumor tissue upon 17-AAG treatment.
The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using (64)Cu-DOTA-cetuximab, which indicates that this approach may be valuable in monitoring the therapeutic response to Hsp90 inhibitor 17-AAG in EGFR-positive cancer patients.
本研究的目的是在PC-3前列腺癌模型中，以非侵入性方式监测表皮生长因子受体（EGFR）对热休克蛋白90抑制剂17-AAG治疗的反应。
给携带PC-3肿瘤的裸鼠腹腔注射17-AAG，然后使用（64）Cu-DOTA-西妥昔单抗通过微型正电子发射断层扫描（microPET）进行成像。进行生物分布研究、免疫荧光染色和蛋白质印迹以验证microPET结果。
PC-3细胞对17-AAG治疗呈剂量依赖性敏感。定量microPET显示，（64）Cu-DOTA-西妥昔单抗在未治疗的肿瘤中具有显著的肿瘤活性积聚（14.6±2.6%ID/g），但在注射后24小时，17-AAG治疗的肿瘤中的摄取显著降低（8.9±1.6%ID/g）。免疫荧光染色和蛋白质印迹均证实17-AAG治疗后肿瘤组织中EGFR表达水平显著降低。
使用（64）Cu-DOTA-西妥昔单抗通过定量PET成功监测了对抗Hsp90治疗的早期反应，这表明该方法在监测EGFR阳性癌症患者对Hsp90抑制剂17-AAG的治疗反应方面可能具有价值。
