Novel albumin-binding multifunctional probe for synergistic enhancement of FL/MR dual-modal imaging and photothermal therapy.

The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility. Albumin can protect GIAs from the recognition and clearance by the mononuclear phagocytic system (MPS). High plasma concentration and long half-life allow GIAs to accumulate continuously in the tumor area through EPR effect and specific uptake of tumor. Because of the prolonged rotational correlation time (τR) of Gd chelates, GIAs exhibited superior MR contrast performance over GIs with more than 3 times enhancement of longitudinal relaxation efficiency (r1). The fluorescence quantum yield and photothermal conversion efficiency of GIAs was also significantly improved due to the constrained geometry, disrupted aggregation and enhanced photothermal stability. This simple and feasible strategy successfully resulted in a synergistic effect for FL/MR dual-modal imaging and photothermal therapy, which can cast a new light for the clinical translation of multifunctional probes.

Inhibitory effects of Ganoderma lucidum triterpenoid on the growth and metastasis of hepatocellular carcinoma.

OBJECTIVE: To investigate the inhibitory effects and mechanisms of triterpenoids from Ganoderma lucidum (G. lucidum triterpenoids) on the growth and metastasis of hepatocellular carcinoma (HCC) both in vitro and in vivo. METHODS: In in-vitro experiments, the inhibitory effects of G. lucidum triterpenoids on human HCC SMMC-7721 cell lines were investigated by observing the proliferation, apoptosis, migration and invasion phenotypes of the cell line and assessing the cell cycles as well as the cell apoptosis and proliferation. In in-vivo experiments, nude mouse SMMC-7721 tumor models were established and divided into control group, treatment group A (low concentration group) and treatment group B (high concentration group) according to the treatment models received. Magnetic resonance imaging (MRI) was performed 3 times on each mouse model to calculate their tumor volumes. The liver and kidney functions of the models were evaluated. Tissues harvested from their solid organs were subjected to HE staining, and the tumor tissues were subjected to HE staining and immunohistochemical staining (E-cad, Ki-67, and Tunel), respectively. RESULTS: i. In in-vitro experiments, G. lucidum triterpenoids could inhibit the growth of human HCC SMMC-7721 cell lines via regulating their proliferation and apoptosis phenotype. ii. In in-vivo experiments, the comparison of tumor volumes of mouse models obtained from the second and third MIR scanning was found to be statistically significant between the control group and treatment group A (P<0.05); and statistically significant differences were also found in the tumor volumes from the second and third MRI scanning between the control group and treatment group B (P<0.05). iii. No significant acute injuries or adverse effects were observed in the liver or kidney of the nude mice. CONCLUSION: G. lucidum triterpenoids could inhibit the growth of tumor cells via blocking their proliferation, accelerating apoptosis, and inhibiting migration and invasion, without marked toxic effects on normal organs and tissues in the body.

Case Report: Treatment of Hypertrophic Cardiomyopathy With Stereotactic Body Radiotherapy.

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics.

BACKGROUND: In experimental animal models, implantation location might influence the heterogeneity and overall development of the tumor, leading to an interpretation bias. PURPOSE: To investigate the effects of implantation location in experimental tumor model using magnetic resonance imaging (MRI) and pathological findings. STUDY TYPE: Prospective. SUBJECTS: Forty-five breast cancer-bearing mice underwent orthotopic (N = 15) and heterotopic (intrahepatic [N = 15] and subcutaneous [N = 15]) implantation. FIELD STRENGTH/SEQUENCE: Sequences including: T1-weighted turbo spin echo sequence, T2-weighted blade sequence, diffusion-weighted imaging, pre- and post-contrast T1 mapping, multi-echo T2 mapping at 3.0 T. ASSESSMENT: MRI was performed at 7, 14, and 21 days after implantation. Native T1, post-contrast T1, T2, and apparent diffusion coefficient (ADC) of tumors, the tumor volume and necrosis volume within tumor were obtained. Lymphocyte cells from H&E staining, Ki67-positive, and CD31-positive cells from immunohistochemistry were determined. STATISTICAL TESTS: One-way analysis of variance and Spearman's rank correlation were performed. P value <0.05 was considered statistically significant. RESULTS: The tumor volume (intrahepatic vs. orthotopic vs. subcutaneous: 587.50 ± 77.62 mm3 vs. 814.00 ± 43.85 mm3 vs. 956.13 ± 119.22 mm3 ), necrosis volume within tumor (89.10 ± 26.60 mm3 vs. 292.41 ± 57.92 mm3 vs. 179.91 ± 31.73 mm3 , respectively), ADC at day 21 (543.41 ± 42.28 vs. 542.92 ± 99.67 vs. 369.83 ± 42.90, respectively), and post-contrast T1 at all timepoints (day 7: 442.00 ± 11.52 vs. 435.00 ± 22.90 vs. 394.33 ± 29.95; day 14: 459.00 ± 26.11 vs. 436.83 ± 26.01 vs. 377.00 ± 27.83; day 21: 463.50 ± 23.49 vs. 458.00 ± 34.28 vs. 375.00 ± 30.55) were significantly different between three groups. Necrosis volumes of subcutaneous and intrahepatic tumors were significantly lower than those of orthotopic tumors. The CD31-positive rate in the intrahepatic implantation was significantly higher than in orthotopic and subcutaneous groups. Necrosis volume (r = -0.71), ADC (r = -0.85), and post-contrast T1 (r = -0.75) were strongly correlated with vascular invasion index. DATA CONCLUSION: Orthotopic and heterotopic tumors have their unique growth kinetics, necrosis volume, and vascular invasion. Non-invasive MR quantitative parameters, including ADC and post-contrast T1, may reflect vascular invasion in mice. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Novel albumin-binding photothermal agent ICG-IBA-RGD for targeted fluorescent imaging and photothermal therapy of cancer.

In this work, we present a novel photothermal agent ICG-IBA-RGD based on albumin-binding strategy for enhanced tumor targeting imaging and photothermal therapy. In vitro and in vivo experiments demonstrated that ICG-IBA-RGD exhibits excellent photothermal conversion capability and high tumor ablation efficiency.

Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model.

BACKGROUND: Bile duct ligation (BDL) in animals is a classical method for mimicking cholestatic fibrosis. Although different surgical techniques have been described in rats and rabbits, mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis. Magnetic resonance imaging (MRI) has made great advances for noninvasive assessment of liver fibrosis. More comprehensive liver fibrotic features of BDL on MRI are important. However, the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed. AIM: To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model. METHODS: Twenty-eight healthy adult male balb/c mice were randomly divided into four groups: sham, week 2 BDL, week 4 BDL, and week 6 BDL. Multiparameter MRI sequences, included magnetic resonance cholangiopancreatography, T1-weighted, T2-weighted, T2 mapping, and pre- and post-enhanced T1 mapping, were performed after sham and BDL surgery. Peripheral blood and liver tissue were collected after MRI. For statistical analysis, Student's t-test and Pearson's correlation coefficient were used. RESULTS: Four mice died after BDL surgery; seven, six, five and six mice were included separately from the four groups. Signal intensities of liver parenchyma showed no difference on TI- and T2-weighted images. Bile duct volume, ΔT1 value, T2 value, and the rate of liver fibrosis increased steadily in week 2 BDL, week 4 BDL and week 6 BDL groups compared with those in the sham group (P < 0.01). Alanine aminotransferase and aspartate transaminase levels initially surged after surgery, followed by a gradual decline over time. Strong correlations were found between bile duct volume (r = 0.84), T2 value (r = 0.78), ΔT1 value (r = 0.62), and hepatic fibrosis rate (all P < 0.01) in the BDL groups. CONCLUSION: The BDL mouse model induces changes that can be observed on MRI. The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.