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New Publication: “Molecular Imaging of Deoxycytidine Kinase Activity Using Deoxycytidine-Enhanced CEST MRI” by Zheng

gliu10 — Thu, 30 May 2019 15:25:24 +0000

Abstract:

Deoxycytidine kinase (DCK) is a key enzyme for the activation of a broad spectrum of nucleoside-based chemotherapy drugs (e.g., gemcitabine); low DCK activity is one of the most important causes of cancer drug-resistance. Noninvasive imaging methods that can quantify DCK activity are invaluable for assessing tumor resistance and predicting treatment efficacy. Here we developed a “natural” MRI approach to detect DCK activity using its natural substrate deoxycytidine (dC) as the imaging probe, which can be detected directly by chemical exchange saturation transfer (CEST) MRI without any synthetic labeling. CEST MRI contrast of dC and its phosphorylated form, dCTP, successfully discriminated DCK activity in two mouse leukemia cell lines with different DCK expression. This dC-enhanced CEST MRI in xenograft leukemic cancer mouse models demonstrated that DCK(+) tumors have a distinctive dynamic CEST contrast enhancement and a significantly higher CEST contrast than DCK(−) tumors (AUC^{0–60 min} = 0.47 ± 0.25 and 0.20 ± 0.13, respectively; P = 0.026, paired Student t test, n = 4) at 1 hour after the injection of dC. dC-enhanced CEST contrast also correlated well with tumor responses to gemcitabine treatment. This study demonstrates a novel MR molecular imaging approach for predicting cancer resistance using natural, nonradioactive, nonmetallic, and clinically available agents. This method has great potential for pursuing personalized chemotherapy by stratifying patients with different DCK activity.

Significance: A new molecular MRI method that detects deoxycytidine kinase activity using its natural substrate deoxycytidine has great translational potential for clinical assessment of tumor resistance and prediction of treatment efficacy.

The full text of the article can be found here: http://cancerres.aacrjournals.org/content/79/10/2775.short

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Congrats to Zheng for winning the OCSMRM YIA award!

gliu10 — Fri, 17 May 2019 15:37:59 +0000

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New publication: Extradomain‑B Fibronectin-Targeted Dextran-Based Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Probe for Detecting Pancreatic Cancer

gliu10 — Mon, 22 Apr 2019 17:12:08 +0000

Congrats to Zheng for the publication on Bioconjugate Chemistry!

The article can be found at the link: https://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.9b00161

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New publication: Sugar‐based biopolymers as novel imaging agents for molecular magnetic resonance imaging

gliu10 — Sun, 03 Feb 2019 16:54:08 +0000

Abstract

Sugar‐based biopolymers have been recognized as attractive materials to develop macromolecule‐ and nanoparticle‐based cancer imaging and therapy. However, traditional biopolymer‐based imaging approaches rely on the use of synthetic or isotopic labeling, and because of it, clinical translation often is hindered. Recently, a novel magnetic resonance imaging (MRI) technology, chemical exchange saturation transfer (CEST), has emerged, which allows the exploitation of sugar‐based biopolymers as MRI agents by their hydroxyl protons‐rich nature. In the study, we reviewed recent studies on the topic of CEST MRI detection of sugar‐based biopolymers. The CEST MRI property of each biopolymer was briefly introduced, followed by the pre‐clinical and clinical applications. The findings of these preliminary studies imply the enormous potential of CEST detectable sugar‐based biopolymers in developing highly sensitive and translatable molecular imaging agents and constructing image‐guided biopolymer‐based drug delivery systems.

Link: https://onlinelibrary.wiley.com/doi/abs/10.1002/wnan.1551

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New publication: CEST MRI of sepsis‐induced acute kidney injury

gliu10 — Wed, 13 Jun 2018 19:36:58 +0000

Abstract

Sepsis‐induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)‐induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i.p. injection of 10 mg/kg LPS. The resulting kidney injury was confirmed by the elevation of serum creatinine and histology. MRI assessments were performed 24 h after LPS injection, including CEST MRI at different B₁ strengths (1, 1.8 and 3 μT), T₁mapping, T₂ mapping and conventional magnetization transfer contrast (MTC) MRI. The CEST MRI results were analyzed using Z‐spectra, in which the normalized water signal saturation (S_sat/S₀) is measured as a function of saturation frequency. Substantial decreases in CEST contrast were observed at both 3.5 and − 3.5 ppm frequency offset from water at all B₁ powers, with the most significant difference obtained at a B₁ of 1.8 μT. The average S_sat/S₀ differences between injured and normal kidneys were 0.07 (0.55 ± 0.04 versus 0.62 ± 0.04, P = 0.0028) and 0.07 (0.50 ± 0.04 versus 0.57 ± 0.03, P = 0.0008) for 3.5 and − 3.5 ppm, respectively. In contrast, the T₁ and T₂ relaxation times and MTC contrast in the injured kidneys did not show a significant change compared with the normal control. Our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys than the changes in T₁, T₂ and MTC effect, indicating its potential clinical utility for molecular imaging of renal diseases.

link: https://onlinelibrary.wiley.com/doi/full/10.1002/nbm.3942

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New publication: MRI detection of bacterial brain abscesses and monitoring of antibiotic treatment using bacCEST

gliu10 — Mon, 19 Mar 2018 14:16:56 +0000

Purpose—To develop a new MRI method to detect and characterize brain abscesses using the CEST contrast inherently carried by bacterial cells, namely bacCEST.

Methods—Bacteria S. aureus (ATCC #49775) and F98 glioma cells were injected stereotactically in the brains of F344 rats to form abscesses and tumors. The CEST signals of brain abscesses (n=4) and tumors (n=4) were acquired using two B1 values (i.e., 1 and 3 μT) and compared. The bacCEST signal of the brain abscesses in the rats (n=3) receiving ampicillin (i.p. 40 mg/kg twice daily) was acquired before, 4 and 10 days after the treatment.

Results—The bacCEST signal of S. aureus was characterized in vitro as a strong and broad signal in the range of 1 to 4 ppm, with the maximum contrast occurring at 2.6 ppm. The CEST signal in S. aureus-induced brain abscesses was significantly higher than that of contralateral parenchyma (P=0.003). Moreover, thanks to their different B1-independece, brain abscesses and tumors could be effectively differentiated (P=0.005) using ΔCEST(2.6ppm,3μT-1μT), defined by the difference between the CEST signal (offset=2.6ppm) acquired using B1 = 3 μT and that of 1 μT. In treated rats, bacCEST MRI could detect the response of bacteria as early as 4 days after the antibiotic treatment (P=0.035).

Conclusion—BacCEST MRI provides a new imaging method to detect, discriminate and monitor bacterial infection in deep-seated organs. Because no contrast agent is needed, such an approach has a great translational potential for detecting and monitoring bacterial infection in deep-seated organs.

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Group Chinese New Year Celebration at Chopsticks!

gliu10 — Mon, 19 Feb 2018 14:21:41 +0000

Let’s keep up the good work for a prolific new year!

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New publication: Phenols as Diamagnetic T2-Exchange Magnetic Resonance Imaging Contrast Agents

gliu10 — Thu, 21 Dec 2017 02:07:52 +0000

Abstract:

While T2-exchange (T2ex) NMR phenomena have been known for decades, only recently there has been a resurgence of interest to develop T2ex MRI contrast agents. One indispensable advantage of T2ex MR agents is the possibility of using non-toxic and/or bio-important diamagnetic compounds with intermediate exchangeable protons. In this study, we screened a library of phenol-based compounds and determined their T2ex contrast (exchange relaxivity, r2ex) at 9.4 T. Our results showed that the T2ex contrast of phenol protons allows them to be detected directly by MRI at a mM concentration level. We also studied the effect of chemical modification of the phenol on the T2ex MRI contrast through modulation of exchange rate and chemical shift. This study provides a guideline for using endogenous and exogenous phenols for T2ex MRI contrast. As a proof-of-principle application, we demonstrated phenol T2ex contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.

Congrats to Jia for the new publication!

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New publication: A dextran-based probe for the targeted magnetic resonance imaging of tumours expressing prostate-specific membrane antigen

gliu10 — Fri, 15 Dec 2017 15:51:50 +0000

Abstract

Safe imaging agents that are able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles that are coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran–ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI. The dextran-based probe could be detected via the contrast that originated from dextran hydroxyl protons, thereby avoiding the need of chemical substitution for radioactive or metallic labeling. Because dextrans are currently used clinically, dextran-based contrast agents may help to extend receptor-targeted imaging to clinical MRI.

Congratulations to Guanshu for the new publication!

Full text of the publication can be found at:

https://www.nature.com/articles/s41551-017-0168-8

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New publication: Characterization of Tumor Vascular Permeability Using Natural Dextrans and CEST MRI

gliu10 — Sun, 03 Dec 2017 21:15:03 +0000

Abstract

Purpose

To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability.

Methods

Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N = 5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40 min after each injection using a dynamic CEST imaging scheme.

Results

All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9 ppm. The detectability and effects of pH and saturation conditions (B₁ and T_sat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant “dexCEST” enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry.

Conclusions

As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

For the full text, please use the following link: http://onlinelibrary.wiley.com/doi/10.1002/mrm.27014/full

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