Ultrashort Echo Time (UTE) imaging of receptor targeted magnetic iron oxide nanoparticles in mouse tumor models

Abstract

Purpose: The purpose of this study was to investigate an ultrashort echo time (UTE) imaging approach for improving the detection of receptor targeted magnetic nanoparticles in cancer xenograft models using positive contrast. Materials and Methods: Iron oxide nanoparticle (IONP) conjugated with tumor targeting ligands were prepared. A 3D UTE gradient echo sequence with the shortest TE of 0.07 msec was evaluated on a 3T magnetic resonance imaging (MRI) scanner using IONP solution, cancer cells bound with targeted IONPs and orthotopic human pancreatic, and breast cancer mouse models administered tumor targeting IONPs. A simulation was performed to analyze contrast-to-noise ratios (CNR) of UTE images and subtraction of the images obtained UTE and longer TE (SubUTE). T2-weighted imaging and T2 relaxometry mapping were applied for comparison and validation. Results: UTE and SubUTE images showed positive contrast in pancreatic tumors accumulated with EGFR targeted ScFvEGFR-IONPs and mammary tumors accumulated with uPAR targeted ATF-IONPs. The positive contrast observed in UTE images was consistent with the negative contrast observed in the T2-weighted images. A flip angle of 10° and a maximal possible TE for the second echo are suitable for SubUTE imaging. Conclusion: UTE imaging is capable of detecting tumor targeted IONPs in vivo with positive contrast in molecular MRI applications.

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…Thus, T 1 signal is dominated and gives rise to bright T 1 MRI contrast as demonstrated in vitro and in vivo by sub-5-nm core size ultrafine IONPs reported by Huang et al [18]. Understanding the interplay between T 1 and T 2 contrast at different core sizes, one can use ultrashort echo time MRI sequence to obtain bright T 1 contrasts with larger sized IONPs as demonstrated in the study in which the accumulation of 10-nm core size IONPs can be observed with ultrashort TE MRI with bright T 1 contrast in orthotopic pancreatic tumors following systemic delivery [55]. To obtain the highest magnetism under size of 100 nm, a recent report showed that 65-nm Fe 3 O 4 nanospheres presented the strongest saturation magnetization (89.24 emu/g) and microwave reflection loss (-30.37 dB at 9.68 GHz), compared with other IONPs at different sizes [56].…”

Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T 1 contrast for heating

“…As a result, positive T 1 contrast for imaging and quantifying IONPs in tissues has not been widely used. However, sequences like sweep imaging with Fourier transformation (SWIFT) and ultrashort echo‐time (UTE) have recently demonstrated utility for detecting and quantifying high IONP concentrations with positive contrast at relatively high iron concentrations. These sequences have a negligible T 2 or weighting because they acquire signal immediately during or after the excitation pulse.…”

Targeted nanoparticles for image‐guided treatment of triple‐negative breast cancer: clinical significance and technological advances

“…41,127 Systemic delivery of uPAR-targeted IONPs led to an accumulation of IONPs in tumors of Balb/c mice bearing 4T1 mouse mammary tumor or nude mice bearing MDA-MB-231 tumor xenografts and generated strong MRI T 2 contrast for tumor MRI. 41 We further demonstrated targeted delivery of NIR dye-labeled IONPs into mice bearing breast tumor xenografts enabling noninvasive multimodal tumor imaging by NIR optical, T 2 -weighted or ultra-short TE MRI, 3D fluorescence tomography, and photoacoustic tomography [128][129][130] (Figure 5). uPAR-targeted nanoprobes significantly enhanced photoacoustic contrast of the tumor margins compared with nontargeted groups, with imaging to depths up to 31 mm.…”

“…Prussian blue staining of the tumor tissue section showed the presence of blue nanoparticle positive cells in the tumor (h). Reproduced and modified with the permission of John Wiley and Sons Inc [126]. B.…”