Ten-Gram-Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis.

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T1 contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten-gram-scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd-salicylate nanoparticles, GdSalNPs-rBSA) with high r1 value of 19.51 mm-1 s-1 and very low r2 /r1 ratio of 1.21 (B0 = 1.5 T) for high-contrast T1 -weighted MRI of tumors. The GdSalNPs-rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t1/2 = 6.13 h), almost no Gd3+ release, and excellent biosafety. Moreover, the GdSalNPs-rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal-to-noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.

[Association of parameters in dynamic contrast-enhanced MRI using reference region model with prognostic factors and molecular subtypes of breast cancer].

OBJECTIVE: To investigate the association of parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using reference region model with prognostic factors and molecular subtypes of breast cancer. METHODS: MRI and pathological data of 50 patients with pathologically confirmed invasive ductal carcinoma of the breast were retrospectively analyzed. Reference region model was applied to analyze pharmacokinetic quantitative parameters including volume transfer constant (RR Ktrans), rate constant (Kep) and the ratio of Ktrans to extracellular space volume (Ktrans/Ve). The associations of the above parameters with prognostic factors and molecular subtypes of breast cancer were analyzed. RESULTS: RR Ktrans and Kep were significantly higher in patients of histological grade 3 compared with those of histological grade 1 & 2 (all P<0.05); and the patients with estrogen receptor (ER)-negative and/or progesterone receptor (PR)-negative also had higher RR Ktrans and Kep than those with ER-positive or PR-positive (all P<0.05). For immunohistochemistry, RR Ktrans and Kep were significantly higher in triple negative breast cancer compared with luminal type breast cancer (all P<0.05). CONCLUSIONS: High RR Ktrans and Kep are associated with poor prognosis of breast cancer, and which can also be used to distinguish molecular subtypes of breast cancer.

Application of MRI Image Based on Computer Semiautomatic Segmentation Algorithm in the Classification Prediction of Breast Cancer Histology.

Objective: The study aimed to investigate the predictive classification accuracy of computer semiautomatic segmentation algorithm for the histological grade of breast tumors through the magnetic resonance imaging (MRI) examination. Methods: Five dynamic contrast-enhanced (DCE) MRI regions of interest (ROIs) were captured using computer semiautomatic segmentation method, referring to the entire tumor area, tumor border area, proximal gland area, middle gland area, and distal gland area. According to the mutual information maximum protocol, the corresponding five ROIs were extracted from diffusion weighted imaging (DWI) combined with DCE-MRI images. To use the features in the nonoverlapping area of DWI image and DCE-MRI image as elements, a single-variable logistic regression model was established corresponding to element characteristics. After multiple training, the model was evaluated using the receiver operating characteristic (ROC) curve and area under curve (AUC). Results: This DCE-MRI combined with DWI was superior to DCE-MRI and DW in the prediction of tumor area features. To use DCE-MRI or DWI alone was less effective than DCE-MRI combined with DWI. The DWI combined DCE-MRI demonstrated good regional segmentation effects in the tumour area, with luminal A value being 0.767 and the area under curve (AUC) value being 0.758. After optimization, the AUC value of the tumor area was 0.929, indicating that classification effects can be enhanced by combining the two imaging methods, which complemented each other. Conclusions: The DWI combined DCE-MRI imaging has improved the early diagnosis effects of breast cancer by predicting the occurrence of breast cancer through the labeling of biomarkers.

pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time.

Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y1 receptor (Y1R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo. Herein, for the first time, we imparted antiphagocytosis capability to Y1R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y1R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.

[MRI diagnosis of osteochondral lesions in the talus and the dynamic follow up analysis after osteochondral transplantation].

OBJECTIVE: To investigate MRI findings of osteochondral lesions in the talus;to evaluate the value of MRI in diagnosing and determining the stage of osteochondral lesions;to analyze the follow up clinical value of MRI in osteochondral transplantation of autologous bone. METHODS: A total of 79 patients from February 2013 to March 2015 had been retrospectively analyzed. All the patients were treated in our hospital. The ankle arthroscopy results were used as the reference standard, and the accuracy of MRI in diagnosis and Hepple staging had been investigated. Fifteen patients with cartilage transplantation of autologous bone were followed up with MRI examination and evaluation of cartilage repair score(MOCART) after one year. The values of MRI in the postoperative follow up were analyzed. RESULTS: Hepple staging of 79 patients was shown as follows:7 cases of stage I, 12 cases of stage II, 24 cases of stage III, 16 cases of stage IV, and 20 cases of stage V. Ankle arthroscopy grading of 59 patients in this group(in addition of 20 cases of stage V):2 cases of grade A, 2 cases of grade B, 4 cases of grade C, 14 cases of grade D, 22 cases of grade E, and 15 cases of grade F. The accuracy rate of MRI in determining Hepple V was set at 100%, and Hepple stage I corresponds to the arthroscopic A, B, C stage, stage II corresponds to D stage, stage III corresponds to E stage, stage IV corresponds to F stage. The accuracy rate of MRI in determining Hepple stage I to IV was 87.5%, 85.7%, 95.4% and 93.3% respectively. After cartilage transplantation of autologous bone, MRI of 15 patients showed cartilage surface in transplanted area was smooth, bone healed well, and the surrounding edema disappeared. The MOCART was 30 to 80 scores with an average score 59.0±15.6;9 cases of these 15 patients were(9/15, 60%) higher than 60 score. CONCLUSIONS: MRI plays a significant role in clinical diagnosis and staging of the talus osteochondral injury. As a method of long term follow up after cartilage transplantation, MRI can well evaluate the rapair of the postoperative osteochondral injury.