18F-labeled magnetic nanoparticles for monitoring anti-angiogenic therapeutic effects in breast cancer xenografts

Abstract

Purpose To develop a novel fluorine-18 (18F)-labeled arginine–glycine–aspartic acid (RGD)-coupled ultra-small iron oxide nanoparticle (USPIO) (hereafter, referred to as 18F-RGD@USPIO) and conduct an in-depth investigation to monitor the anti-angiogenic therapeutic effects by using a novel dual-modality PET/MRI probe. Methods The RGD peptide and 18F were coupled onto USPIO by click chemistry. In vitro experiments including determination of stability, cytotoxicity, cell binding of the obtained 18F-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 18F-RGD@USPIO before and after treatment. Imaging findings were validated by histological analysis with regard to β3-integrin expression (CD61 expression), microvascular density (CD31 expression), and proliferation (Ki-67 expression). Results Excellent stability, low toxicity, and good specificity to endothelial of 18F-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, 18F-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 β3 expression were noted in the bevacizumab therapy group than the placebo group, which were consistent with the imaging results. Conclusion PET/MRI with the dual-modality nanoprobe, 18F-RGD@USPIO, can be implemented as a noninvasive approach to monitor the therapeutic effects of anti-angiogenesis in breast cancer model in vivo.

Fibronectin-Targeting and Cathepsin B-Activatable Theranostic Nanoprobe for MR/Fluorescence Imaging and Enhanced Photodynamic Therapy for Triple Negative Breast Cancer

“…To investigate the fibronectin-targeting and CTSB-active capability of Pep-SQ@USPIO in vivo, we investigated MR/NIRF imaging of mice bearing MDA-MB-231 or MCF-7 tumors, respectively. Previously, we reported that the USPIO core of Pep-SQ@USPIO could display a remarkable T2 enhanced contrast effect . As illustrated in Figure A, after the Pep-SQ@USPIO injection, a significant MRI signal intensity decrease was observed in the tumor site of MDA-MB-231 tumor-bearing mice.…”

“…Previously, we reported that the USPIO core of Pep-SQ@USPIO could display a remarkable T2 enhanced contrast effect. 56 As illustrated in Figure 4A, after the Pep-SQ@USPIO injection, a significant MRI signal intensity decrease was observed in the tumor site of MDA-MB-231 tumor-bearing mice. According to the time activity curves of T2 relaxation time determined by the T2 mapping sequence (Figure 4B), the average T2 relaxation time in the MDA-MB-231 tumor site decreased continuously until 4 h postinjection, after which it increased slightly at 6 h. In contrast, at the same time after injection, the signal of MCF-7 tumor showed a weaker decrease (Figure 4A).…”

Nanotechnology as a Versatile Tool for 19F-MRI Agent’s Formulation: A Glimpse into the Use of Perfluorinated and Fluorinated Compounds in Nanoparticles

“…Since every imaging technique has its unique benefits and drawbacks, combining imaging modalities (multimodal imaging) can offer synergistic advantages over a single modality to compensate for each imaging method's inherent limitations, subsequently to obtain more accurate and informative images. In fact, in most studies, multimodal imaging has become a trend both in research and clinic applications for meticulous examinations [21][22][23]. Table 1 compares the different parameters of all the imaging modalities discussed including optical imaging, PAI, US, CT, PET, SPECT, X-ray, MRI.…”

Nanotechnology-Assisted Cell Tracking

“…As some exam-ples, the conjugation of 99mTc with silica [202], iron oxide [203] or gold [204] NPs was exploited for SPECT/MRI or SPECT/CT imaging of tumors in preclinical mouse models. Likewise, the conjugation of 18F with iron oxide NP was found effective for dual imaging with PET/MRI of stem cell biodistribution [205] as well as for monitoring anti-angiogenic therapeutic effects in breast cancer xenograft mouse models [206] and diagnosis of rectal cancer in clinics [207]. Importantly, since PET/MRI systems have become operational worldwide, several imaging protocols involving the use of 18F for whole body scanning in oncology are currently under standardization for patient management in clinics [208].…”