Concurrent Dual-Contrast Enhancement Using Fe3O4 Nanoparticles to Achieve a CEST Signal Controllability

Traditional T (2) magnetic resonanceimaging(MRI) contrast agents have defects inherent to negative contrast agents,while chemical exchange saturation transfer (CEST) contrast agentscan quantify substances at trace concentrations. After reaching acertain concentration, iron-based contrast agents can "shutdown" CEST signals. The application range of T (2) contrast agents can be widened through a combinationof CEST and T (2) contrast agents, whichhas promising application prospects. The purpose of this study isto develop a T (2) MRI negative contrastagent with a controllable size and to explore the feasibility of dualcontrast enhancement by combining T (2) withCEST contrast agents. The study was carried out in vitro with HCT-116 human colon cancer cells. A GE SIGNA Pioneer 3.0 Tmedical MRI scanner was used to acquire CEST images with differentsaturation radio-frequency powers (1.25/2.5/3.75/5 & mu;T) by 2Dspin echo-echo planar imaging (SE-EPI). Magnetic resonanceimage compilation (MAGiC) was acquired by a multidynamic multiecho2D fast spin-echo sequence. The feasibility of this dual-contrastenhancement method was assessed by scanning electron microscopy, transmissionelectron microscopy, Fourier transform infrared spectroscopy, dynamiclight scattering, & zeta; potential analysis, inductively coupledplasma, X-ray photoelectron spectroscopy, X-ray powder diffraction,vibrating-sample magnetometry, MRI, and a Cell Counting Kit-8 assay.The association between the transverse relaxation rate r (2) and the pH of the iron-based contrast agents was analyzedby linear fitting, and the linear relationship between the CEST effectin different B-1 fields and pH was analyzed by the ratiomethod. Fe3O4 nanoparticles (NPs) with a meanparticle size of 82.6 & PLUSMN; 22.4 nm were prepared by a classicalprocess, and their surface was successfully modified with -OHactive functional groups. They exhibited self-aggregation in an acidicenvironment. The CEST effect was enhanced as the B-1 fieldincreased, and an in vitro pH map was successfullyplotted using the ratio method. Fe3O4 NPs couldstably serve as reference agents at different pH values. At a concentrationof 30 & mu;g/mL, Fe3O4 NPs "shut down"the CEST signals, but when the concentration of Fe3O4 NPs was less than 10 & mu;g/mL, the two contrast agentscoexisted. The prepared Fe3O4 NPs had almostno toxicity, and when their concentration rose to 200 & mu;g/mLat pH 6.5 or 7.4, they did not reach the half-maximum inhibitory concentration(IC50). Fe3O4 magnetic NPs with acontrollable size and no toxicity were successfully synthesized. Bycombining Fe3O4 NPs with a CEST contrast agent,the two contrast agents could be imaged simultaneously; at higherconcentrations, the iron-based contrast agent "shut down"the CEST signal. An in vitro pH map was successfullyplotted by the ratio method. CEST signal inhibition can be used torealize the pH mapping of solid tumors and the identification of tumoractive components, thus providing a new imaging method for tumor efficacyevaluation.