Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study.

BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

High-Quantum-Yield Ultrasmall Ln2O3 (Ln = Eu, Tb, or Dy) Nanoparticle Colloids in Aqueous Media Obtained via Photosensitization.

Fluorescent nanoparticles used in biomedical applications should be stable in their colloidal form in aqueous media and possess a high quantum yield (QY). We report ultrasmall Ln2O3 (Ln = Eu, Tb, or Dy) nanoparticle colloids with high QYs in aqueous media. The nanoparticles are grafted with hydrophilic and biocompatible poly(acrylic acid) (PAA) to ensure colloidal stability and biocompatibility and with organic photosensitizer 2,6-pyridinedicarboxylic acid (PDA) for achieving a high QY. The PAA/PDA-Ln2O3 nanoparticle colloids were nearly monodispersed and ultrasmall (particle diameter: ∼2 nm). They exhibited excellent colloidal stability with no precipitation after synthesis (>1.5 years) in aqueous media, very low cellular toxicity, and very high absolute QYs of 87.6, 73.6, and 2.8% for Ln = Eu, Tb, and Dy, respectively. These QYs are the highest reported so far for lanthanides in aqueous media. Therefore, the results suggest their high potential as sensitive optical or imaging probes in biomedical applications.

Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent.

Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M-1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1ß, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2.

Optimization of spectrally selective 180° radiofrequency pulse timings in J-difference editing (MEGA) of lactate.

PURPOSE: J-Difference editing (MEGA) provides an effective spectroscopic means of selectively measuring low-concentration metabolites having weakly coupled spins. The fractional inphase and antiphase coherences are determined by the radiofrequency (RF) pulses and inter-RF pulse intervals of the sequence. We examined the timings of the spectrally selective editing 180° pulses (E180) in MEGA-PRESS to maximize the edited signal amplitude in lactate at 3T. METHODS: The time evolution of the lactate spin coherences was analytically and numerically calculated for non-volume localized and single-voxel localized MEGA sequences. Single-voxel localized MEGA-PRESS simulations and phantom experiments were conducted for echo time (TE) 60-160 ms and for all possible integer-millisecond timings of the E180 pulses. Optimized E180 timings of 144, 103, and 109 ms TEs, tailored with simulation and phantom data, were tested in brain tumor patients in vivo. Lactate signals, broadened to singlet linewidths (~6 Hz), were compared between simulation, phantom, and in vivo data. RESULTS: Theoretical and experimental data indicated consistently that the MEGA-edited signal amplitude and width are sensitive to the E180 timings. In volume-localized MEGA, the lactate peak amplitudes in E180-on and difference spectra were maximized at specific E180 timings for individual TEs, largely due to the chemical-shift displacement effects. The E180 timings for maximum lactate peak amplitude were different from those of maximum inphase coherence in in vivo linewidth situations. CONCLUSION: In in vivo MEGA editing, the E180 pulse timings can be effectively used for manipulating the inphase and antiphase coherences and increasing the edited signal amplitude, following TE optimization.

Impact of fractional amplitude of low-frequency fluctuations in motor- and sensory-related brain networks on spinal cord injury severity.

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p < .05). Higher fALFF values were observed in the putamen and thalamus, and were negatively associated with motor and sensory function (p < .05). In conclusion, alterations in the neural activity of the motor- and sensory-related networks of the brain were observed in complete-SCI and incomplete-SCI patients. Moreover, plastic changes in these brain regions were associated with motor and sensory function.

Aberrant functional connectivity of neural circuits associated with thought-action fusion in patients with obsessive-compulsive disorder.

BACKGROUND: Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. METHODS: Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. RESULTS: The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. CONCLUSIONS: Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

Connectome-based predictive models using resting-state fMRI for studying brain aging.

Changes in the brain with age can provide useful information regarding an individual's chronological age. studies have suggested that functional connectomes identified via resting-state functional magnetic resonance imaging (fMRI) could be a powerful feature for predicting an individual's age. We applied connectome-based predictive modeling (CPM) to investigate individual chronological age predictions via resting-state fMRI using open-source datasets. The significant feature for age prediction was confirmed in 168 subjects from the Southwest University Adult Lifespan Dataset. The higher contributing nodes for age production included a positive connection from the left inferior parietal sulcus and a negative connection from the right middle temporal sulcus. On the network scale, the subcortical-cerebellum network was the dominant network for age prediction. The generalizability of CPM, which was constructed using the identified features, was verified by applying this model to independent datasets that were randomly selected from the Autism Brain Imaging Data Exchange I and the Open Access Series of Imaging Studies 3. CPM via resting-state fMRI is a potential robust predictor for determining an individual's chronological age from changes in the brain.

Clinical adaptation of synthetic MRI-based whole brain volume segmentation in children at 3 T: comparison with modified SPM segmentation methods.

PURPOSE: To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. METHODS: In total, 106 children aged 4.7-18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. RESULTS: Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87-0.98; r = 0.78-0.96; relative volume difference other than CSFV = 6.8-18.5% [SyMRI vs. SPM T1] and 11.3-22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78-0.91. The Bland-Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject's age (p < 0.05). CONCLUSION: SyMRI and SPM segmentation results were consistent except for CSFV, which supports routine clinical use of SyMRI-based volumetry in pediatric neuroimaging. However, caution should be taken in the interpretation of the CSF segmentation results.

Time-saving synthetic magnetic resonance imaging protocols for pediatric neuroimaging: impact of echo train length and bandwidth on image quality.

BACKGROUND: Synthetic MRI is a time-efficient imaging technique that provides both quantitative MRI and contrast-weighted images simultaneously. However, a rather long single scan time can be challenging for children. OBJECTIVE: To evaluate the clinical feasibility of time-saving synthetic MRI protocols adjusted for echo train length and receiver bandwidth in pediatric neuroimaging based on image quality assessment and quantitative data analysis. MATERIALS AND METHODS: In total, we included 33 children ages 1.6-17.4 years who underwent synthetic MRI using three sets of echo train length and receiver bandwidth combinations (echo train length [E]12-bandwidth [B in KHz]22, E16-B22 and E16-B83) at 3 T. The image quality and lesion conspicuity of synthetic contrast-weighted images were compared between the suggested protocol (E12-B22) and adjusted protocols (E16-B22 and E16-B83). We also compared tissue values (T1, T2, proton-density values) and brain volumetry. RESULTS: For the E16-B83 combination, image quality was sufficient except for 15.2% of T1-W and 3% of T2-W fluid-attenuated inversion recovery (FLAIR) images, with remarkable scan time reduction (up to 35%). The E16-B22 combination demonstrated a comparable image quality to E12-B22 (P>0.05) with a scan time reduction of up to 8%. There were no significant differences in lesion conspicuity among the three protocols (P>0.05). Tissue value measurements and brain tissue volumes obtained with the E12-B22 protocol and adjusted protocols showed excellent agreement and strong correlations except for gray matter volume and non-white matter/gray matter/cerebrospinal fluid volume in E12-B22 vs. E16-B83. CONCLUSION: The adjusted synthetic protocols produced image quality sufficient or comparable to that of the suggested protocol while maintaining lesion conspicuity with reduced scan time. The quantitative values were generally consistent with the suggested MRI-protocol-derived values, which supports the clinical application of adjusted protocols in pediatric neuroimaging.

Enhanced Tumor Imaging Using Glucosamine-Conjugated Polyacrylic Acid-Coated Ultrasmall Gadolinium Oxide Nanoparticles in Magnetic Resonance Imaging.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (davg = 1.76 nm). Higher positive (brighter or T1) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T1 MRI contrast agents in tumor imaging via GlcN effects.

In vivo evaluation of PEGylated-liposome encapsulating gadolinium complexes for gadolinium neutron capture therapy.

Gadolinium neutron capture therapy (GdNCT) is a form of binary radiotherapy. It utilizes nuclear reactions that occur when gadolinium-157 is irradiated with thermal neutrons, producing high-energy γ-rays and Auger electrons. Herein, we evaluate the potential of GdNCT for cancer treatment using PEGylated liposome incorporated with an FDA-approved MRI contrast agent. The clinical gadolinium complex (Gadovist®) was successfully encapsulated inside the aqueous core of PEGylated liposomes by repeated freeze and thaw cycling. At a concentration of 152 µM Gd, the Gd-liposome showed high cytotoxicity upon thermal-neutron irradiation. In animal experiments, when a CT26 tumor model was administered with Gd-liposomes (19 mg 157Gd per kg) followed by 20-min irradiation of thermal neutron at a flux of 1.94 × 104 cm-2 s-1, tumor growth was suppressed by 43%, compared to that in the control group, on the 23rd day of post-irradiation. After two-cycle GdNCT treatment at a 10-day interval, tumor growth was more efficiently retarded. On the 31st day after irradiation, the weight of the excised tumor in the GdNCT group (38 mg 157Gd per kg per injection) was only 30% of that of the control group. These results demonstrate the potential of GdNCT using PEGylated liposomes containing MRI contrast agents in cancer treatment.

Development of a Stereotactic Radiosurgery Frame Adapter for a Multichannel MRI Coil.

BACKGROUND: The usage of multichannel brain MRI coils, which have several advantages over single-channel brain coils used for stereotactic radiosurgery (SRS), requires a frame adapter device to fit the frames inside the multichannel brain coils. However, such a frame adapter has not been developed until now. OBJECTIVE: to develop an SRS frame adapter for multichannel MRI coils and verify the geometrical accuracy and signal-to-noise ratio (SNR) of the MR images obtained using multichannel MRI coils. METHODS: We fabricated an SRS frame adapter for a 48-channel MRI coil using a three-dimensional (3D) printer. Furthermore, we obtained phantom and human-brain MR images with a 3.0 Tesla MRI scanner using multi- and single-channel coils. Computed tomography (CT) phantom images were also obtained as reference. We compared the coordinate errors of the multi- and single-channel coils to evaluate the geometrical accuracy. Two neurosurgeons measured the coordinates. In addition, we compared the SNR differences between multi- and single-channel coils using the T1- and T2-weighted brain images. RESULTS: For the CT coordinate measurements, the correlation coefficient r = 1 and p < 0.001 with respect to the 3 axes (Δx, Δy, and Δz) and 3D errors (Δr) showed no interpersonal differences between the 2 neurosurgeons. The results obtained using the T1-weighted images showed that a multichannel coil had smaller coordinate errors in Δx, Δy, Δz, and Δr than that observed in case of a single-channel coil (p < 0.001). In case of the SNR measurements, most of the brain areas showed higher SNRs when using a multichannel coil compared with that observed when using a single-channel coil in the T1- and T2-weighted images. CONCLUSION: Compared with single-channel coils, the use of multichannel MRI coils with a newly developed frame adapter is expected to ensure successful SRS treatments with improved geometrical accuracy and SNR.

PEGylated liposome encapsulating nido-carborane showed significant tumor suppression in boron neutron capture therapy (BNCT).

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on nuclear reactions that occur when boron-10 is irradiated with neutrons, which result in the ejection of high-energy alpha particles. Successful BNCT requires the efficient delivery of a boron-containing compound to effect high concentrations in tumor cells while minimizing uptake in normal tissues. In this study, PEGylated liposomes were employed as boron carriers to maximize delivery to tumors and minimize uptake in the reticuloendothelial system (RES). The water-soluble potassium salt of nido-7,8-carborane, nido-carborane, was chosen as the boron source due to its high boron content per molecule. Nido-carborane was encapsulated in the aqueous cores of PEGylated liposomes by hydrating thin lipid films. Repeated freezing and thawing increased nido-carborane loading by up to 47.5 ± 3.1%. The average hydrodynamic diameter of the prepared boronated liposomes was determined to be 114.5 ± 28 nm through dynamic light scattering (DLS) measurement. Globular liposomes approximately 100 nm in diameter were clearly visible in transmission electron microscope (TEM) images. The viability of tumor cells following BNCT with 70 µM nido-carborane was reduced to 17.1% compared to irradiated control cells, which did not contain boronated liposomes. Confocal microscopy revealed that fluorescently labeled liposomes injected into the tail veins of mice were deeply and evenly distributed in tumor tissues and localized in the cytoplasm of tumor cells. When mice were properly shielded with a 12 mm-thick polyethylene board during in-vivo irradiation at a thermal neutron flux of 1.94 × 104/cm2·sec, almost complete tumor suppression was achieved in tumor models injected with boronated liposomes (21.0 mg 10B/kg). Two BNCT cycles spaced 10 days apart further enhanced the therapeutic anti-tumor effect, even when the dose was lowered to 10.5 mg 10B/kg. No notable weight loss was observed in the tumor models during the BNCT study.

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles.

The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s-1mM-1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

The neural correlates of thought-action fusion in healthy adults: A functional magnetic resonance imaging study.

BACKGROUND: Thought-action fusion (TAF) represents an individual's belief that a thought is like action. Inflated TAF has been considered a central mechanism for developing obsessive thoughts. However, the neural mechanisms underlying TAF are yet unknown. METHODS: We recruited 32 healthy men to participate in a functional magnetic resonance imaging (fMRI) study. Whereas inside the 3T MRI scanner, participants were asked to read negative statements describing the expectation of bad events associated with close persons (CPs condition) or neutral persons (NPs condition). They also completed the assessment of TAF and obsessive-compulsive (OC) symptoms. RESULTS: Both CP and NP conditions commonly activated the lingual gyrus, caudate nucleus, precuneus, and several areas of the frontal cortex. Importantly, many of these regions were positively correlated with measures of OC symptoms, especially for the CP condition. The CP condition showed higher activation in the insula and temporal gyrus than the NP condition. In contrast, the NP condition evoked higher activation in regions associated with mentalizing, such as the medial prefrontal cortex and dorsal anterior cingulate cortex than the CP condition. CONCLUSIONS: We introduced and validated a TAF-induction paradigm suitable for fMRI studies and characterized the neural circuits engaged during this paradigm. Further studies using this task may help us to better understand how dysfunctions in TAF neural processing may contribute to psychiatric conditions such as obsessive-compulsive disorder.

Effects of a Mixed Reality-based Cognitive Training System Compared to a Conventional Computer-assisted Cognitive Training System on Mild Cognitive Impairment: A Pilot Study.

BACKGROUND: Mixed reality (MR) technology, which combines the best features of augmented reality and virtual reality, has recently emerged as a promising tool in cognitive rehabilitation therapy. OBJECTIVE: To investigate the effectiveness of an MR-based cognitive training system for individuals with mild cognitive impairment (MCI). METHODS: Twenty-one individuals aged 65 years and older who had been diagnosed with MCI were recruited for this study and were divided into two groups. Participants in the MR group (n=10, aged 70.5±4.2 years) received 30 minutes of training 3 times a week for 6 weeks using a newly developed MR-based cognitive training system. Participants in the control group (n=11, aged 72.6±5.3 years) received the same amount of training using a conventional computer-assisted cognitive training system. Both groups took the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) both before and after intervention. To determine the effect of the intervention on cognitive function, we compared the difference in each group's CERAD-K scores. RESULTS: There was a statistically significant interaction between intervention (MR group vs control group) and time (before vs after intervention) as assessed by the Constructional Recall Test. The individuals with MCI who participated in the MR training showed significantly improved performance in visuospatial working memory compared with the individuals with MCI who participated in the conventional training. CONCLUSION: An MR-based cognitive training system can be used as a cognitive training tool to improve visuospatial working memory in individuals with MCI.

Synthesis and Evaluation of Manganese(II)-Based Ethylenediaminetetraacetic Acid-Ethoxybenzyl Conjugate as a Highly Stable Hepatobiliary Magnetic Resonance Imaging Contrast Agent.

In this study, we designed and synthesized a highly stable manganese (Mn2+)-based hepatobiliary complex by tethering an ethoxybenzyl (EOB) moiety with an ethylenediaminetetraacetic acid (EDTA) coordination cage as an alternative to the well-established hepatobiliary gadolinium (Gd3+) chelates and evaluated its usage as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent (CA). This new complex exhibits higher r1 relaxivity (2.3 mM-1 s-1) than clinically approved Mn2+-based hepatobiliary complex Mn-DPDP (1.6 mM-1 s-1) at 1.5 T. Mn-EDTA-EOB shows much higher kinetic inertness than that of clinically approved Gd3+-based hepatobiliary MRI CAs, such as Gd-DTPA-EOB and Gd-BOPTA. In addition, in vivo biodistribution and MRI enhancement patterns of this new Mn2+ chelate are comparable to those of Gd3+-based hepatobiliary MRI CAs. The diagnostic efficacy of the new complex was demonstrated by its enhanced tumor detection sensitivity in a liver cancer model using in vivo MRI.

Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics.

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

Relaxometric, Optical and Cell Viability Properties of D-Glucuronic Acid Coated Cr2O3 Nanoparticles.

D-glucuronic acid-coated ultrasmall chromium oxide (Cr2O3) nanoparticles were synthesized by a one-pot polyol method and their relaxometric and optical properties were investigated. The as-synthesized D-glucuronic acid-coated nanoparticles were amorphous owing to ultrasmall particle diameters (davg = 2.0 nm), whereas orthorhombic Cr2O3 nanoparticles with two size groups (davg = 3.6 and 5.7 nm) were observed after thermogravimetric analysis (900 °C) as a result of particle growth. The nanoparticles exhibited size-dependent UV-visible absorption maxima at 238, 274, and 372 nm with increasing particle diameter, corresponding to band gaps of 5.13, 4.45, and 3.28 eV, respectively. D-glucuronic acid-coated ultrasmall Cr2O3 nanoparticles revealed low water proton relaxivities of r1 = 0.05 s-1mM-1 and r2 = 0.20 s-1mM-1, consistent with the antiferromagnetic property of Cr2O3. They showed good biocompatibility up to 500 µM of Cr.

Longitudinal Water Proton Relaxivity and In Vivo T1 MR Images of Mixed Zn(II)/Gd(III) Oxide Nanoparticles.

Mixed Zn(II)/Gd(III) oxide nanoparticles (~8 mole%Zn) with d(avg) of 2.1 nm were synthesized. The D-glucuronic acid coated Zn(II)/Gd(III) oxide nanoparticles showed a longitudinal water proton relaxivity (r1) of 12.3 s⁻¹mM⁻¹ with r2/r1 = 1.1, corresponding to an ideal condition for T1 MRI contrast agent. We attribute this to reduced magnetization of the mixed nanoparticles owing to non-magnetic Zn in the nanoparticles. Their effectiveness as a T1 MRI contrast agent was confirmed by acquiring In Vivo T1 MR images of a mouse after intravenous injection.