Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
Mol Pharm. 2011 Apr 4;8(2):621-8. doi: 10.1021/mp100446t. Epub 2011 Feb 15.
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/V(0), 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 days 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 antitumor effects of VEGF₁₂₁/rGel at the early stage of treatment. This preclinical study should be helpful in accelerating anticancer drug development and promoting the clinical translation of molecular imaging.
在这项研究中，我们应用了多重正电子发射断层扫描（PET）探针来监测乳腺癌 VEGF₁₂₁/rGel 治疗过程中的葡萄糖代谢、细胞增殖、肿瘤缺氧和血管生成。两次腹腔注射 12mg/kg 的 VEGF₁₂₁/rGel，导致肿瘤生长初期延迟，但在肿瘤治疗停止后 4 天肿瘤又开始生长。肿瘤生长速度的平均比值（V/V(0)）分别为治疗后第 1、3、7 和 14 天的 1.11 ± 0.07、1.21 ± 0.10、1.58 ± 0.36 和 2.64 ± 0.72。同时，VEGF₁₂₁/rGel 治疗组的 V/V₀比值分别为治疗后第 1、3、7 和 14 天的 1.04 ± 0.06、1.05 ± 0.11、1.09 ± 0.17 和 1.86 ± 0.36。VEGF₁₂₁/rGel 治疗导致 ¹⁸F-FPPRGD2 的摄取在第 1 天（24.0 ± 8.8%，p < 0.05）和第 3 天（36.3 ± 9.2%，p < 0.01）显著降低，与基线相比，第 14 天缓慢恢复至基线水平。¹⁸F-FMISO 的摄取在治疗肿瘤中于第 1 天（23.9 ± 15.7%，p < 0.05）和第 3 天（51.4 ± 29.4%，p < 0.01）增加，与对照组相比。在第 7 和 14 天，¹⁸F-FMISO 的摄取恢复到基线水平。在治疗肿瘤中，¹⁸F-FLT 的摄取减少约 13.0 ± 4.5%，在第 3 天减少 25.0 ± 4.4%（p < 0.01）。与对照组相比，VEGF₁₂₁/rGel 治疗的肿瘤中¹⁸F-FDG 的摄取没有明显变化。体外分析相关生物标志物的结果支持了影像学研究。总之，用 4 种 PET 示踪剂进行的纵向影像学研究表明，多探针在治疗早期定量测量 VEGF₁₂₁/rGel 抗肿瘤作用方面具有可行性和实用性。这项临床前研究将有助于加速抗癌药物的开发，并促进分子影像学的临床转化。
