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Abstract To overcome the problems of commercial magnetic resonance imaging (MRI) contrast agents (CAs) (i.e., small molecule Gd chelates), we have proposed a new concept of Gd macrochelates based on the coordination of Gd3+ and macromolecules, e.g., poly(acrylic acid) (PAA). To further decrease the r 2/r 1 ratio of the reported Gd macrochelates that is an important factor for T 1 imaging, in this study, a superior macromolecule hydrolyzed polymaleic anhydride (HPMA) was found to coordinate Gd3+. The synthesis conditions were optimized and the generated Gd-HPMA macrochelate was systematically characterized. The obtained Gd-HPMA29 synthesized in a 100 L of reactor has a r 1 value of 16.35 mM−1 s−1 and r 2/r 1 ratio of 2.05 at 7.0 T, a high Gd yield of 92.7% and a high product weight (1074 g), which demonstrates the feasibility of kilogram scale facile synthesis. After optimization of excipients and sterilization at a high temperature, the obtained Gd-HPMA30 formulation has a pH value of 7.97, osmolality of 691 mOsmol/kg water, density of 1.145 g/mL, and viscosity of 2.2 cP at 20 ℃ or 1.8 cP at 37 ℃, which meet all specifications and physicochemical criteria for clinical injections indicating the immense potential for clinical applications. Graphical Abstract

Cadmium tellurium quantum dots (CdTe QDs) as one of the most widely used QDs have been reported the toxicity and biosafety in recent years, little work has been done to reduce their toxicity however. Based on the mechanisms of toxicity of CdTe QDs on liver target organs such as oxidative stress and apoptosis previously reported by other researchers, we investigated the mechanism of action of trace element selenium (Se) to mitigate the hepatotoxicity of CdTe QDs. The experimental results showed that Se-Met at 40–140 μg L−1 could enhance the function of intracellular antioxidant defense system and the molecular structure of related antioxidant enzymes by reduce the production of ROS by 45%, protecting the activity of antioxidants and up-regulating the expression of selenoproteins with antioxidant functions, Gpx1 increase 225% and Gpx4 upregulated 47%. In addition, Se-Met could alleviate CdTe QDs-induced apoptosis by regulating two apoptosis-inducing factors, as intracellular caspase 3/9 expression levels were reduced by 70% and 87%, decreased Ca2+ concentration, and increased mitochondrial membrane potential measurements. Overall, this study indicates that Se-Met has a significant protective effect on the hepatotoxicity of CdTe QDs. Se-Met can be applied to the preparation of CdTe QDs to inhibit its toxicity and break the application limitation.

Abstract Magnetic resonance imaging (MRI) has been widely using in clinical diagnosis, and contrast agents (CAs) can improve the sensitivity MRI. To overcome the problems of commercial Gd chelates-based T 1 CAs, commercial magnetic iron oxide nanoparticles (MIONs)-based T 2 CAs, and reported exceedingly small MIONs (ES-MIONs)-based T 1 CAs, in this study, a facile co-precipitation method was developed to synthesize biodegradable and biocompatible ES-MIONs with excellent water-dispersibility using poly (aspartic acid) (PASP) as a stabilizer for T 1-weighted MRI of tumors. After optimization of the synthesis conditions, the final obtained ES-MION9 with 3.7 nm of diameter has a high r 1 value (7.0 ± 0.4 mM−1 s−1) and a low r 2/r 1 ratio (4.9 ± 0.6) at 3.0 T. The ES-MION9 has excellent water dispersibility because of the excessive –COOH from the stabilizer PASP. The pharmacokinetics and biodistribution of ES-MION9 in vivo demonstrate the better tumor targetability and MRI time window of ES-MION9 than commercial Gd chelates. T 1-weighted MR images of aqueous solutions, cells and tumor-bearing mice at 3.0 T or 7.0 T demonstrate that our ES-MION9 has a stronger capability of enhancing the MRI contrast comparing with the commercial Gd chelates. The MTT assay, live/dead staining of cells, and H&E-staining indicate the non-toxicity and biosafety of our ES-MION9. Consequently, the biodegradable and biocompatible ES-MION9 with excellent water-dispersibility is an ideal T 1-weighted CAs with promising translational possibility to compete with the commercial Gd chelates.

Abstract To surmount the major concerns of commercial small molecule Gd chelates and reported Gd‐based contrast agents (GBCAs) for magnetic resonance imaging (MRI), a new concept of organogadolinium macrochelates (OGMCs) constructed from the coordination between Gd3+ and macromolecules is proposed. A library of macromolecules were screened for Gd3+ coordination, and two candidates [i.e., poly(acrylic acid) (PAA), and poly(aspartic acid) (PASP)] succeeded in OGMC formation. Under optimized synthesis conditions, both Gd‐PAA12 and Gd‐PASP11 OGMCs are outstanding T1‐weighted CAs owing to their super high r1 values (> 50 mm−1 s−1, 3.0 T) and ultralow r2/r1 ratios (< 1.6, 3.0 T). The ferromagnetism of OGMCs is completely different from the paramagnetism of commercial and reported GBCAs. The ferromagnetism is very weak (Ms

Paraganglioma (PGL) is a neuroendocrine tumor that arises from the sympathetic or parasympathetic paraganglia. Primary thyroid PGL is extremely rare. PGL may be difficult to diagnose on frozen sections because its histopathological features, such as polygonal tumor cells with eosinophilic cytoplasm arranged irregularly, overlap with those of thyroid follicular adenoma. We present a case of thyroid PGL in a female patient and provide a detailed description of the patient’s clinicopathologic characteristics. Cervical computed tomography showed a left thyroid mass with uneven density. Intraoperative frozen section analysis showed an uneven fibrous septa and rich networks of delicate vessels surrounding tumor cell nests. The tumor cells were polygonal or epithelioid with eosinophilic cytoplasm, arranged in a nest, trabecular, or organoid pattern were and diagnosed as thyroid follicular adenoma. However, in postoperative immunohistochemistry, these were diagnosed as thyroid PGL. The postoperative recovery was uneventful. The patient showed no signs of tumor recurrence or metastasis until 16 months of follow-up. Herein, we summarize the characteristic features of thyroid PGL based on frozen section analysis. In the appropriate clinical context, its proper use as diagnostic and differential diagnostic management strategies is recommended.