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Assessing the effectiveness of nanomedicines involves evaluating the drug content at the target site. Currently, most research focuses on monitoring the signal responses from loaded drugs, neglecting the changes caused by the nanohosts. Here, we propose a strategy to quantitatively evaluate the content of loaded drugs by detecting the signal variations resulting from the alterations in the microenvironment of the nanohosts. Specifically, hyperpolarized (HP) 129 Xe atoms are employed as probes to sense the nanohosts' environment and generate a specific magnetic resonance (MR) signal that indicates their accessibility. The introduction of drugs reduces the available space in the nanohosts, leading to a crowded microenvironment that hinders the access of the 129 Xe atoms. By employing 129 Xe atoms as a signal source to detect the alterations in the microenvironment, we constructed a three-dimensional (3D) map that indicated the concentration of the nanohosts and established a linear relationship to quantitatively measure the drug content within the nanohosts based on the corresponding MR signals. Using the developed strategy, we successfully quantified the uptake of the nanohosts and drugs in living cells through HP 129 Xe MR imaging. Overall, the proposed HP 129 Xe atom-sensing approach can be used to monitor alterations in the microenvironment of nanohosts induced by loaded drugs and provides a new perspective for the quantitative evaluation of drug presence in various nanomedicines.

We report a dual-signal chemical exchange saturation transfer (Dusi-CEST) strategy for drug delivery and detection in living cells. The two signals can be detected by operators in complex environments. This strategy is demonstrated on a cucurbit[6]uril (CB[6]) nanoparticle probe, as an example. The CB[6] probe is equipped with two kinds of hydrophobic cavities: one is found inside CB[6] itself, whereas the other exists inside the nanoparticle. When the probe is dispersed in aqueous solution as part of a hyperpolarized 129 Xe NMR experiment, two signals appear at two different chemical shifts (100 and 200 ppm). These two resonances correspond to the NMR signals of 129 Xe in the two different cavities. Upon loading with hydrophobic drugs, such as paclitaxel, for intracellular drug delivery, the two resonances undergo significant changes upon drug loading and cargo release, giving rise to a metric enabling the assessment of drug delivery success. The simultaneous change of Dusi-CEST likes a mobile phone that can receive both LTE and Wi-Fi signals, which can help reduce the occurrence of false positives and false negatives in complex biological environments and help improve the accuracy and sensitivity of single-shot detection.

MRI with hyperpolarized 129 Xe can achieve low-concentration detection. Herein, nanoparticle-coated perfluorooctyl bromide (PFOB) was developed as a 129 Xe MRI contrast agent with a moderate exchange rate, sufficient stability and feasible surface modification. The α v β 3 integrin overexpressed by non-small-cell lung cancer A549 cells was successfully detected by 129 Xe MRI with high specificity through adequate surface modifications.

Purpose: CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free-base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection., Methods: To test these newly identified CEST agents, we acquired a series of Z-spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor-bearing mice, and MR images were acquired to assess detection feasibility in vivo., Results: Based on the Z-spectra, the inner nitrogen protons in free-base porphyrins and chlorin resonate from -8 to -13.5 ppm from water, far shifted from the majority of endogenous metabolites (0-4 ppm) and Nuclear Overhauser enhancements (-1 to -3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5-12 ppm). The exchange rates are sufficiently slow to intermediate (500-9000 s -1 ) to allow robust detection and were sensitive to substituents on the porphyrin ring., Conclusion: These results highlight the capabilities of free-base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications., (© 2019 International Society for Magnetic Resonance in Medicine.)

A fluorinated aza-BODIPY derivative BDPF was developed as a small molecule contrast agent, which displayed highly efficient near infrared fluorescence/photoacoustic/19F MR tri-modality tumor imaging.

Nano contrast agents (Nano CA) are nanomaterials used to increase contrast in the medical magnetic resonance imaging (MRI). However, the related relaxation mechanism of the Nano CA is not clear yet and little significant breakthrough in relaxivity enhancement has been achieved. Herein, a new hydrophilic Gd-DOTA complex functionalized with different chain length of PEG was synthesized and incorporated into graphene quantum dots (GQD) to obtain paramagnetic graphene quantum dots (PGQD). We performed a variable-temperature and variable-field intensity NMR study in aqueous solution on the water exchange and rotational dynamics of three different chain lengths of PGQD. The optimal GQD with paramagnetic chain length shows a great improvement in performance on 1 H NMR relaxometric studies. In vitro results demonstrated that the relaxivity of the designed PGQD could be controlled by regulating the PEG length, and its relaxivity was ∼16 times higher than that of current commercial MRI contrast agents (e.g., Gd-DTPA), on a "per Gd" basis. The relaxivity of the Nano CA can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the paramagnetic GQD with the enhanced T 1 relaxivity. The fabricated PGQDs with suitable PEG length got the best relaxivity at 1.5 T. After intravenous injection, its feeding process by solid tumor could even be monitored by clinically used 1.5 T MRI scanners. This research will also provide an excellent platform for the design and synthesis of highly effective MR contrast agents.

Background: The rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. We aimed to afford a potential strategy to pose both T 1 - and T 2 -weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy., Results: Theranostic nanocomposites Mn-porphyrin&Fe 3 O 4 @SiO 2 @PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T 1 - and T 2 -weighted MRI and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposites specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r 2 /r 1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH 5.0, suggesting the NCs could act as an ideal T 1 /T 2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T 1 and T 2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites., Conclusion: The synthesized nanocomposites exhibited highly sensitive MRI contrast function no matter in solution, cells or in vivo by synergistically enhancing positive and negative magnetic resonance imaging signals. The nanocomposites showed great potential for integrating imaging diagnosis and drug controlled release into one composition and providing real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy.

Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play an important role in regulating the vital functions of living organisms. Knowledge of their biodistribution in real-time could help diagnose a variety of conditions. However, existing methods of biothiol detection are invasive and require assays. Herein we report a molecular biosensor for biothiol detection using the nuclear spin resonance of (129)Xe. The (129)Xe biosensor consists of a cryptophane cage encapsulating a xenon atom and an acrylate group. The latter serves as a reactive site to covalently bond biothiols through a thiol-addition reaction. The biosensor enables discrimination of Cys from Hcy and GSH through the chemical shift and average reaction rate. This biosensor can be detected at a concentration of 10 μM in a single scan and it has been applied to detect biothiols in bovine serum solution. Our results indicate that this biosensor is a promising tool for the real-time imaging of biothiol distributions.

Objectives To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. Methods We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. Results AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P  <  .05). Conclusion The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. Advances in knowledge This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE. [ABSTRACT FROM AUTHOR]

As a promising cell tracking technology, 19F MRI suffers from low sensitivity. Here, fluorinated nanoemulsions with a unified 19F signal and paramagnetic relaxation enhancement were developed as 19F MRI cellular tracers with high stability, size controllability, biocompatibility, cellular uptake, and dual-modality for sensitive in vivo RAW264.7 cell tracking. [ABSTRACT FROM AUTHOR]

Tracking drugs with 19F MRI would be beneficial for developing theranostics and optimizing drug therapy. To this end, a fluorinated dendritic amphiphile with high 19F MRI sensitivity and biocompatibility has been developed for 19F MRI tracking of doxorubicin (DOX)-loaded liposomes in mice, which may provide an effective platform to in vivo trace various drugs with 19F MRI. [ABSTRACT FROM AUTHOR]

A new magnetic resonance imaging (MRI) molecular sensor for hydrogen sulfide detection and imaging using the nuclear spin resonance of hyperpolarized 129Xe is developed. The designed MRI sensor employs cryptophane for NMR sensing, together with an azide group serving as a reaction site. It demonstrates a 'proof-of-concept' that a fluorescent H2S probe can be linked to a xenon-binding cryptophane and thereby converted into an MRI probe, which could provide a very generalizable template. [ABSTRACT FROM AUTHOR]

Keywords: 19F MRI; Biosensors; Fluorescence Imaging; Hypoxia; Nitroreductase EN 19F MRI Biosensors Fluorescence Imaging Hypoxia Nitroreductase 1 1 1 12/07/22 20221212 NES 221212 B Eine bimodale Bildgebungssonde b FCy7-NO SB 2 sb wurde eingesetzt, um die bei Lungenkrebs überexprimierte Nitroreduktase in vivo abzubilden, wie Xin Zhou et al. in ihrem Forschungsartikel berichten (e202213495). 19F MRI, Biosensors, Fluorescence Imaging, Hypoxia, Nitroreductase Die Integration zweier komplementärer Bildgebungstechnologien in FCy7-NO SB 2 sb ermöglicht einen empfindlichen Nachweis von Nitroreduktase in einem breiten Konzentrationsbereich ohne Gewebetiefenbegrenzung. [Extracted from the article]

Hyperpolarization is one of the methods for NMR signal enhancement. NMR sensitivity can be further enhanced by combining hyperpolarization with chemical exchange saturation transfer (CEST), which termed “Hyper‐CEST”. A H2S sensor is reported that contains a cryptophane group for NMR sensing and a naphthalimide group for fluorescence sensing, together with an azide group as the reaction site. Upon reacting with H2S, the fluorescence and 129Xe NMR signal changes, which may provide a universal template for converting a fluorescence sensor into an 129Xe Hyper‐CEST MRI sensor. More information can be found in the Communication by X. Zhou, M. Liu, et al. on page 7648. [ABSTRACT FROM AUTHOR]

Riboflavin and its derivatives are the most important coenzymes in vivo metabolism, and are closely related to life activities. In this paper, the first photolysis 129Xe biosensor was developed by combining cryptophane-A with riboflavin moiety, which showed photosensitivity recorded by hyperpolarized 129Xe NMR/MRI technology with an obvious chemical shift change of 5.3 ppm in aqueous solution. Cellular fluorescence imaging confirmed that the biosensor could be enriched in MCF-7 cells, and MTT assays confirmed that the cytotoxicity was enhanced after irradiation. Findings suggested that the biosensor has a potential application in tumor targeting and the inhibition of tumor cell proliferation after photodegradation. [Display omitted] • We proposed a novel biosensor for tumor cells targeting and inhibition based on 129Xe NMR/MRI and fluorescence imaging. • A 129Xe NMR/MRI biosensor is constructed by introducing the riboflavin moiety for monitoring by photolysis. • A photosensitive 129Xe NMR/MRI biosensor for BCRP-targeted uptake and light-induced inhibition of tumor cells is developped. [ABSTRACT FROM AUTHOR]