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Mol Pharm. 2011 Apr 4;8(2):621-8. doi: 10.1021/mp100446t. Epub 2011 Feb 15.

Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment.

Author information

1
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.

Abstract

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.

PMID:
21280671
PMCID:
PMC3070817
DOI:
10.1021/mp100446t
[Indexed for MEDLINE]
Free PMC Article

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