Targeted Imaging of Lung Cancer with Hyperpolarized 129Xe MRI Using Surface-Modified Iron Oxide Nanoparticles as Molecular Contrast Agents

Abstract

Hyperpolarized 129Xe (HP 129Xe) MRI enables functional imaging of various lung diseases but has been scarcely applied to lung cancer imaging. The aim of this study is to investigate the feasibility of targeted imaging of lung cancer with HP 129Xe MRI using surface-modified iron oxide nanoparticles (IONPs) as molecular targeting contrast agents. A mouse model of lung cancer (LC) was induced in nine mice by intra-peritoneal injection of urethane. Three months after the urethane administration, the mice underwent lung imaging with HP 129Xe MRI at baseline (0 h). Subsequently, the LC group was divided into two sub-groups: mice administered with polyethylene glycol-coated IONPs (PEG-IONPs, n = 4) and folate-conjugated dextran-coated IONPs (FA@Dex-IONPs, n = 5). The mice were imaged at 3, 6, and 24 h after the intravenous injection of IONPs. FA@Dex-IONPs mice showed a 25% reduction in average signal intensity at cancer sites at 3 h post injection, and a 24% reduction at 24 h post injection. On the other hand, in PEG-IONPs mice, while a signal reduction of approximately 28% was observed at cancer sites at 3 to 6 h post injection, the signal intensity was unchanged from that of the baseline at 24 h. Proton MRI of LC mice (n = 3) was able to detect cancer five months after urethane administration, i.e., later than HP 129Xe MRI (3 months). Furthermore, a significant decrease in averaged 1H T2 values at cancer sites was observed at only 6 h post injection of FA@Dex-IONPs (p < 0.05). As such, the targeted delivery of IONPs to cancer tissue was successfully imaged with HP 129Xe MRI, and their surface modification with folate likely has a high affinity with LC, which causes overexpression of folate receptors.

Advancing MRI with magnetic nanoparticles: a comprehensive review of translational research and clinical trials

“…The overexpression of folate receptor alpha in the majority of ovarian malignancies have led to the development of anti-folate receptor alpha SPIONs that can reliably detect ovarian tumors. 151 Lung tumors can also be visualised by taking advantage of the overexpressed folate receptor, as Kimura et al 152 showed by using polyethylene glycol-coated and dextran-coated SPIONs. Furthermore, using a hipoxia-sensitive metronidazole moiety, Yang et al 153 was able to accurately measure hipoxia in lung tumors using T 1 -weighted sequences, predicting tumor development.…”

MRI Application and Challenges of Hyperpolarized Carbon-13 Pyruvate in Translational and Clinical Cardiovascular Studies: A Literature Review

“…In SEOP, circularly polarized light is exploited to optically pump rubidium (Rb) electrons and generate a highly spin-polarized Rb gas; the spin polarization is then transferred to noble gas nuclei through spin-exchange collisions. 129 Xe proved to be a suitable gas for clinical studies where it can be used for functional MRI in the lungs [24][25][26] among other applications [27,28]. Techniques such as parahydrogen-induced polarization (PHIP) and dynamic nuclear polarization (DNP) showed great promise for the production of injectable hyperpolarized contrast agents in the liquid state.…”

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“…Additionally, aptamers and peptides functionalization of NPs is used for liver cancer [37,38] visualization. The PEG coated MIONPs, and dextran (DEX)-coated IONPs conjugating folate on their surface are perspective molecular contrast agents for lungs cancer detection [39].…”