Non-invasive in-vivo tracking of T-cells by magnetic resonance imaging (MRI) can lead to a better understanding of many pathophysiological situations, including AIDS, cancer, diabetes, graft rejection, etc. However, an efficient MRI contrast agent and a reliable technique to track non-phagocytic T-cells are needed. We report a novel superparamagnetic nano-sized iron-oxide particle, IOPC-NH2 series particles, coated with polyethylene glycol (PEG), with high transverse relaxivity (250 s−1mM−1), thus useful for MRI studies. IOPC-NH2 particles are the first reported magnetic particles that can label rat and human T-cells with over 90% efficiency, without using transfection agents, HIV-1 transactivator peptide, or electroporation. IOPC-NH2 particles do not cause any measurable effects on T-cell properties. Infiltration of IOPC-NH2-labeled-T-cells can be detected in a rat model of heart-lung transplantation by in-vivo MRI. IOPC-NH2 is potentially valuable contrast agents for labeling a variety of cells for basic and clinical cellular MRI studies, e.g., cellular therapy.

Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.

Purpose-In this study, we investigated the labeling efficiency and magnetic resonance imaging (MRI) signal sensitivity of a newly synthesized, nano-sized iron oxide particle (IOP) coated with polyethylene glycol (PEG), designed by Industrial Technology Research Institute (ITRI).Procedures-Macrophages, bone-marrow-derived dendritic cells, and mesenchymal stem cells (MSCs) were isolated from rats and labeled by incubating with ITRI-IOP, along with three other iron oxide particles in different sizes and coatings as reference. These labeled cells were characterized with transmission electron microscopy (TEM), light and fluorescence microscopy, phantom MRI, and finally in vivo MRI and ex vivo magnetic resonance microscopy (MRM) of transplanted hearts in rats infused with labeled macrophages.Results-The longitudinal (r 1 ) and transverse (r 2 ) relaxivities of ITRI-IOP are 22.71 and 319.2 s −1 mM −1 , respectively. TEM and microscopic images indicate the uptake of multiple ITRI-IOP particles per cell for all cell types. ITRI-IOP provides sensitivity comparable or higher than the other three particles shown in phantom MRI. In vivo MRI and ex vivo MRM detect punctate spots of hypointensity in rejecting hearts, most likely caused by the accumulation of macrophages labeled by ITRI-IOP.Conclusion-ITRI-IOP, the nano-sized iron oxide particle, shows high efficiency in cell labeling, including both phagocytic and non-phagocytic cells. Furthermore, it provides excellent sensitivity in T 2 *-weighted MRI, and thus can serve as a promising contrast agent for in vivo cellular MRI.

Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.

BackgroundMRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver‐specific contrast agents which enhance lesions in T2‐weighted images. Iron oxide nano‐particle m‐PEG‐silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial.PurposeTo evaluate the safety and clinical validity of IOP Injection as MRI contrast agent in diagnosing HCC.Study typeProspective.SubjectsA total of 52 subjects (61.6 ± 11.05 years, 45 males/7 females) with suspected HCC.Field Strength/Sequence1.5 T, T1‐weighted in/opposed phase, T2*‐weighted gradient echo, T2‐weighted fast spin echo, true fast imaging with steady‐state free precession.AssessmentAdverse effects and clinical monitoring were recorded throughout the 5‐day study. Two independent readers (M.G.H. with 30 years of experience, S.P.K. with 26 years of experience) made the diagnosis. The diagnostic performance of IOP‐enhanced MRI was evaluated with sensitivity and positive predictive value by comparing to the pathology reports from subsequent hepatic resection. The number of lesions with various sizes and degrees of differentiation detected by IOP‐enhanced MRI was assessed. The relative change in signal intensities over time was indirectly measured from acquired images.Statistical TestsSensitivity and positive predictive value were used to evaluate the diagnostic performance of IOP‐enhanced MRI. Prevalence‐adjusted and bias‐adjusted 𝜅 coefficient was used to assess the interreader variability.ResultsNo serious adverse event related to IOP Injection was found. IOP Injection enhanced the lesion‐to‐liver contrast ratio in T2*‐weighted images by 50.1% ± 4.8%. IOP‐enhanced MRI detected HCC with 100% sensitivity by subject and 96% sensitivity by lesion. IOP Injection visualized subtle vascular invasion as filling defect within vessels in true fast imaging with steady‐state free precession (TrueFISP) images.Data ConclusionIOP Injection was safe and efficacious as MRI contrast agent in diagnosing HCC in a limited group of subjects.Evidence Level2.Technical EfficacyStage 2.