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18 F-labeled magnetic nanoparticles for monitoring anti-angiogenic therapeutic effects in breast cancer xenografts
Ist Teil von
Journal of nanobiotechnology, 2019-10, Vol.17 (1), p.105
Ort / Verlag
England
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
To develop a novel fluorine-18 (
F)-labeled arginine-glycine-aspartic acid (RGD)-coupled ultra-small iron oxide nanoparticle (USPIO) (hereafter, referred to as
F-RGD@USPIO) and conduct an in-depth investigation to monitor the anti-angiogenic therapeutic effects by using a novel dual-modality PET/MRI probe.
The RGD peptide and
F were coupled onto USPIO by click chemistry. In vitro experiments including determination of stability, cytotoxicity, cell binding of the obtained
F-RGD@USPIO were carried out, and the targeting kinetics and bio-distribution were tested on an MDA-MB-231 tumor model. A total of 20 (n = 10 per group) MDA-MB-231 xenograft-bearing mice were treated with bevacizumab or placebo (intraperitoneal injections of bevacizumab or a volume-equivalent placebo solution at the dose of 5 mg/kg for consecutive 7 days, respectively), and underwent PET/CT and MRI examinations with
F-RGD@USPIO before and after treatment. Imaging findings were validated by histological analysis with regard to β
-integrin expression (CD61 expression), microvascular density (CD31 expression), and proliferation (Ki-67 expression).
Excellent stability, low toxicity, and good specificity to endothelial of
F-RGD@USPIO were confirmed. The best time point for MRI scan was 6 h post-injection. No intergroup differences were observed in tumor volume development between baseline and day 7. However,
F-RGD@USPIO binding was significantly reduced after bevacizumab treatment compared with placebo, both on MRI (P < 0.001) and PET/CT (P = 0.002). Significantly lower microvascular density, tumor cell proliferation, and integrin β
expression were noted in the bevacizumab therapy group than the placebo group, which were consistent with the imaging results.
PET/MRI with the dual-modality nanoprobe,
F-RGD@USPIO, can be implemented as a noninvasive approach to monitor the therapeutic effects of anti-angiogenesis in breast cancer model in vivo.