Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment.
Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment.
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DOI：
10.1021/mp100446t
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发表时间：
2011-04-04
影响因子：
4.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Yang M;Gao H;Sun X;Yan Y;Quan Q;Zhang W;Mohamedali KA;Rosenblum MG;Niu G;Chen X
在这项研究中，我们应用多重正电子发射断层扫描（PET）探针监测葡萄糖代谢，细胞增殖，肿瘤缺氧和血管生成的VEGF 121/rGel治疗乳腺癌。腹腔内给予两个剂量的12 mg/kg VEGF 121/rGel，导致肿瘤生长的初始延迟，但在肿瘤治疗停止后4天恢复生长。平均肿瘤生长率表示为V/V0，在第1、3、7和14天分别为1.11 ± 0.07、1.21 ± 0.10、1.58 ± 0.36和2.64 ± 0.72。同时，VEGF 121/rGel治疗组在第1、3、7和14天的V/V0比值分别为1.04 ± 0.06、1.05 ± 0.11、1.09 ± 0.17和1.86 ± 0.36。VEGF 121/rGel治疗导致在第1天（24.0 ± 8.8%，p < 0.05）和第3天（36.3 ± 9.2%，p < 0.01）相对于基线显著降低的18F-FPPRGD 2摄取，其在第14天缓慢恢复至基线。与对照组相比，在第1天（23.9 ± 15.7%，p < 0.05）和第3天（51.4 ± 29.4%，p < 0.01），经处理的肿瘤中18F-FMISO摄取增加。在第7天和第14天，18F-FMISO摄取恢复到基线水平。治疗肿瘤中FLT摄取的相对减少在第1天和第3天分别约为13.0 ± 4.5%和25.0 ± 4.4%（p < 0.01）。与对照组相比，VEGF 121/rGel处理的肿瘤的18F-FDG摄取没有显著变化。相关生物标志物的离体分析支持成像结果。总体而言，使用4种PET示踪剂的纵向成像研究证明了多重探针在治疗早期定量测量VEGF 121/rGel抗肿瘤作用的可行性和有用性。该研究有助于加快抗肿瘤药物的研发，促进分子影像学的临床转化。
In this study, we applied multiplexed positron emission tomography (PET) probes to monitor glucose metabolism, cellular proliferation, tumor hypoxia and angiogenesis during VEGF121/rGel therapy of breast cancer. Two doses of 12 mg/kg VEGF121/rGel, administered intraperitoneally, resulted in initial delay of tumor growth, but the growth resumed 4 days after tumor treatment was stopped. The average tumor growth rate expressed as V/V0, were 1.11 ± 0.07, 1.21 ± 0.10, 1.58 ± 0.36 and 2.64 ± 0.72 at days 1, 3, 7 and 14, respectively. Meanwhile, the VEGF121/rGel treatment group showed V/V0 ratios of 1.04 ± 0.06, 1.05 ± 0.11, 1.09 ± 0.17 and 1.86 ± 0.36 at days 1, 3, 7 and 14, respectively. VEGF121/rGel treatment led to significantly decreased uptake of 18F-FPPRGD2 at day 1 (24.0 ± 8.8%, p < 0.05) and day 3 (36.3 ± 9.2%, p < 0.01), relative to the baseline, which slowly recovered to the baseline at day 14. 18F-FMISO uptake was increased in the treated tumors at day 1 (23.9 ± 15.7%, p < 0.05) and day 3 (51.4 ± 29.4%, p < 0.01), as compared to the control group. At day 7 and 14, 18F-FMISO uptake restored to the baseline level. The relative reductions in FLT uptake in treated tumors were approximately 13.0 ± 4.5% at day 1 and 25.0 ± 4.4% (p < 0.01) at day 3. No significant change of 18F-FDG uptake was observed in VEGF121/rGel treated tumors, compared with the control group. The imaging findings were supported by ex vivo analysis of related biomarkers. Overall, longitudinal imaging studies with 4 PET tracers demonstrated the feasibility and usefulness of multiplexed probes for quantitative measurement of anti-tumor effects of VEGF121/rGel at the early stage of treatment. This pre-clinical study should be helpful in accelerating anti-cancer drug development and promoting the clinical translation of molecular imaging.
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影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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