Compared to traditional branched polymers with Gd(III) chelates conjugated on their surface, branched polymers with Gd(III) chelates as the internal skeleton are considered to be a reasonable strategy for preparing efficient magnetic resonance imaging contrast agents. Herein, the Gd(III) ligand DOTA was chosen as the internal skeleton; four different molecular weights (3.5, 5.3, 8.6, and 13.1 kDa) and degrees of branching poly-DOTA branched polymers (P1, P2, P3, and P4) were synthesized by a simple “A2 + B4”-type one-pot polymerization. The Gd(III) chelates of these poly-DOTA branched polymers (P1-Gd, P2-Gd, P3-Gd, and P4-Gd) display excellent kinetic stability, which is significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol and slightly lower than that of cyclic Gd-DOTA. The T 1 relaxivities of P1-Gd, P2-Gd, P3-Gd, and P4-Gd are 29.4, 38.7, 44.0, and 47.9 Gd mM–1 s–1, respectively, at 0.5 T, which are about 6–11 times higher than that of Gd-DOTA (4.4 Gd mM–1 s–1). P4-Gd was selected for in vivo magnetic resonance angiography (MRA) because of its high kinetic stability, T 1 relaxivity, and good biosafety. The results showed excellent MRA effect, sensitive detection of vascular stenosis, and prolonged observation window as compared to Gd-DOTA. Overall, Gd(III) chelates of poly-DOTA branched polymers are good candidates of MRI probes, providing a unique design strategy in which Gd chelation can occur at both the interior and surface of the poly-DOTA branched polymers, resulting in excellent relaxivity enhancement. In vivo animal MRA studies of the probe provide possibilities in discovering small vascular pathologies.
Background: About 20%-40% of patients diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) will develop invasive cancer at the time of excision. Improving the preoperative diagnosis of DCIS is important for surgical planning. Purpose: To establish an MRI-based radiomics nomogram for preoperatively evaluating the upstaging of DCIS patients and help with risk stratification. Study Type: Retrospective. Population: A total of 227 patients (50.5 AE 9.7 years; 67 upstaged DCIS) were divided into training (n = 109), internal (n = 47), and external (n = 71) validation cohort. Field Strength/Sequence: 1.5-T or 3-T, dynamic contrast-enhanced (DCE) imaging, and diffusion-weighted imaging (DWI). Assessment: DCIS lesions were manually segmented using ITK-SNAP software and 1304 radiomic features were extracted from DCE, DWI, and apparent diffusion coef-ficient (ADC) maps, respectively. A radscore was calculated by a random forest algo-rithm based on DCIS upstaging-related radiomic features, which selected by a coarse-to-fine method including interclass correlation coefficient, single-factor anal-ysis, and the least absolute shrinkage and selection operator (LASSO) method. Uni-variate and multivariate logistic regression was used to analyze the independent risk factors, including age, location, lesion size, estrogen receptor (ER) status, and other clinico-pathologic factors. Finally, Mann-Whitney U tests were performed to com-pare the differences in radscore between low/intermediate and high nuclear grade groups for pure DCIS patients. Statistical Tests: Student's t-tests or Mann-Whitney U tests, chi-square-tests, or Fisher's-tests, univariate and multivariate logistic regression analysis, calibration curve, Youden index, the area under the curve (AUC), Delong test, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. Results: Eight important radiomic features (two from ADC, three from DWI, and three from DCE) were selected for calculating radscore. Clinical model including age and ER was established with AUCs of 0.747 and 0.738 in the internal and external validation cohorts, respectively. A combined model integrating age, estrogen receptor (ER), and radscore were also constructed with AUCs of 0.887 and 0.881. Further subgroup analysis showed that pure DCIS patients with different nuclear grade have significant differences in radscore. Data Conclusion: Multisequence MRI radiomics may preoperatively evaluate the upstaging of DCIS and might provide personalized image-based clinical decision support. Evidence Level: 4. Technical Efficacy: Stage 2.
Nanophotothermal agents that provide efficient and precise treatment at tumor sites are attracting increasing attention in biomedicine. In particular, the method combination of nanophotothermal agents and magnetic resonance imaging (MRI) shows great promise for biomedical therapeutic applications. Herein, a simple nanophotothermal agent with dopamine multivalent-modified polyaspartic acid chelated superparamagnetic iron oxide (SPIO) and ferric ion (SPIO@PAsp-DAFe/PEG) was developed for MRI-guided near-infrared photothermal therapy (PTT). SPIO@PAsp-DAFe/PEG was random SPIO nanocluster with good water solubility, had a diameter of 57.8 ± 7.8 nm in DLS, negatively charged surface (zeta potential = −11 mV), exhibited good stability and outstanding photothermal conversion efficiency (35.4%), and produced superior magnetic resonance enhanced imaging. In the experiment with tumor-bearing mice, the MRI not only monitored the accumulation of SPIO@PAsp-DAFe/PEG nanocomposites enhanced by near-infrared irradiation after intravenous administration but also determined the appropriate time window for PTT. With the use of MRI-guided near-infrared therapy, the SPIO@PAsp-DAFe/PEG nanocomposites provided excellent therapeutic effects, confirming their great potential as effective MRI/PTT therapeutic agents.
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