title: Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment.
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.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Xilin
authors.initials: X
authors.lastname: Sun
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Quan
authors.forename: Wendy
authors.initials: W
authors.lastname: Zhang
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Mohamedali
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenblum
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D054789:Ribosome Inactivating Proteins, Type 1 / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D054789:Ribosome Inactivating Proteins, Type 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; C025674:GEL protein, Gelonium multiflorum; D005947:Glucose