Abstract
Magnetic resonance imaging (MRI) could be the ideal diagnostic modality for early rheumatoid arthritis (RA). Vascular cell adhesion molecule-1 (VCAM-1) is highly expressed in synovial locations in patients with RA, which could be a potential target protein for RA diagnosis. The peptide VHPKQHR (VHP) has a high affinity to VCAM-1. To make the contrast agent to target RA at an early stage, we used VHP and ultrasmall paramagnetic iron oxide (USPIO) to synthesize UVHP (U stands for USPIO) through a chemical reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The size of UVHP was 6.7 nm; the potential was −27.7 mV, and the r 2/r 1 value was 1.73. Cytotoxicity assay exhibited that the cell survival rate was higher than 80% at even high concentrations of UVHP (Fe concentration 200 µg/mL), which showed the UVHP has low toxicity. Compared with no TNF-α stimulation, VCAM-1 expression was increased nearly 3-fold when mouse aortic endothelial cells (MAECs) were stimulated with 50 ng/mL TNF-α; cellular Fe uptake was increased very significantly with increasing UVHP concentration under TNF-α treatment; cellular Fe content was 17 times higher under UVHP with Fe concentration 200 µg/mL treating MAECs. These results indicate that UVHP can target overexpression of VCAM-1 at the cellular level. RA mice models were constructed with adjuvant-induced arthritis. In vivo MRI and biodistribution results show that the signal intensity of knee joints was increased significantly and Fe accumulation in RA model mice compared with normal wild-type mice after injecting UVHP 24 h. These results suggest that we have synthesized a simple, low-cost, and less toxic contrast agent UVHP, which targeted VCAM-1 for early-stage RA diagnosis and generates high contrast in T1-weighted MRI.
Highlights
Rheumatoid arthritis (RA), a chronic systemic immune disease (Firestein, 2003), has a global prevalence of 0.5% to 1% (AbdelNasser et al, 1997; Kvien, 2004)
Compared with ultrasmall paramagnetic iron oxide (USPIO), the particle size of the UVHP increased to 6.69 ± 2.78 nm (Figure 2D), and the zeta potential changed to −27.7 mV (Figure 2F), which should be attributed to the VHP connecting to the USPIO surface
dynamic light scattering (DLS) analysis showed that the hydrodynamic sizes of USPIO and UVHP were approximately 4 and 60 nm, respectively (Figure 2E)
Summary
Rheumatoid arthritis (RA), a chronic systemic immune disease (Firestein, 2003), has a global prevalence of 0.5% to 1% (AbdelNasser et al, 1997; Kvien, 2004). Because of the high resolution of the tissue, MRI may be one of the most ideal methods used clinically for the early diagnosis of RA (Østergaard et al, 2008; Hou et al, 2020). MRI contrast agents are divided into longitudinal relaxation contrast agents (T1-weighted contrast agents) and transverse relaxation contrast agents (T2-weighted contrast agents) according to their principle of action (Zhao et al, 2021). T1weighted contrast agent shortens the longitudinal relaxation time of the tissue and enhances the signal; T2-weighted contrast agent shortens the transverse relaxation time of the tissue and weakens the signal. As the T2 signal is dark, and T1 is a bright signal, and the high magnetic moment of the T2 contrast agent may cause magnetic-susceptibility artifacts (Na et al, 2009; Zhou et al, 2020), and human vision prefers bright signals; T1 contrast agent is more prevalently used than T2 in a clinical setting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
