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

Liu, Guanshu; Banerjee, Sangeeta Ray; Yang, Xing; Yadav, Nirbhay N.; Lisok, Ala; Jabłońska, Anna; Xu, Jiadi; Li, Yuguo; Pomper, Martin G.; Zijl, Peter van

doi:10.1038/s41551-017-0168-8

Cited by 61 publications

(79 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, several variations of CEST, such as amide proton transfer (APT), glutamate CEST, creatine CEST, CEST imaging of glucose and its derivatives, paramagnetic agent CEST, and acidoCEST, have been developed to detect endogenous and exogenous agents. To further quantify the exchange rate, which is relevant to the intracellular or extracellular pH, a ratiometric approach, using the ratio of two CEST signals that have different dependences on the exchange rate but the same dependences on other non‐specific factors (e.g., solute pool concentration), was also developed .…”

Section: Introductionmentioning

confidence: 99%

Ratiometric NOE(−1.6) contrast in brain tumors

2018

NMR in Biomedicine

View full text Add to dashboard Cite

Recently, a new nuclear Overhauser enhancement (NOE)‐mediated saturation transfer effect at around −1.6 ppm from water, termed NOE(−1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(−1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(−1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(−1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non‐specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi‐solid MT effects, and provides a more specific NOE coupling rate‐ and solute transverse relaxation rate‐weighted signal. Animal studies show that the ratiometric NOE(−1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(−1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(−1.6) signal in tumors.

show abstract

Section: Introductionmentioning

confidence: 99%

Ratiometric NOE(−1.6) contrast in brain tumors

2018

NMR in Biomedicine

View full text Add to dashboard Cite

show abstract

“…[9] To enhance the sensitivity of such agents for receptor-based molecular imaging in vivo, we planned to use an established polymeric platform to increase the concentration of salicylic acid moieties within a single molecular entity (Figure 1A). For this purpose, a commercially available polymeric material, poly(maleic anhydride), and its derivatives were used to graft salicylic acid units onto the multimeric backbone.…”

Section: Resultsmentioning

confidence: 99%

Salicylic Acid‐Based Polymeric Contrast Agents for Molecular Magnetic Resonance Imaging of Prostate Cancer

Banerjee

Song

Yang

et al. 2018

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an innovative molecular imaging technique in which contrast agents are labeled by saturating their exchangeable proton spins by radio-frequency irradiation. Salicylic acid and its analogues are a promising class of highly sensitive, diamagnetic CEST agents. Herein, polymeric agents grafted with salicylic acid moieties and a known high-affinity ligand targeting prostate-specific membrane antigen in approximately 10:1 molar ratio were synthesized to provide sufficient MRI sensitivity and receptor specificity. The proton-exchange properties of the contrast agent in solution and in an experimental murine model are reported to demonstrate the feasibility of receptor-targeted CEST MRI of prostate cancer. Furthermore, the CEST imaging data were validated with an In-labeled analogue of the agent by in vivo single photon emission computed tomographic imaging and tissue biodistribution studies.

show abstract

“…Full Z spectra were acquired by sweeping the saturation offsets from ‐3 ppm to +3 ppm (step size 0.2 ppm) using a fat‐suppressed RARE sequence with a continuous wave presaturation pulse of B 1 = 1.8 µT and 3 s with acquisition parameters: T R /T E = 5000/5 ms, RARE factor = 10, number of averages = 2, slice number = 1, slice thickness = 1 mm, matrix size = 64 × 64 with partial FT acceleration to 64 × 40, field of view = 25 mm × 25 mm 2 , total acquisition time = 20.7 min. It should be noted that a weaker B 1 (i.e., 1.8 µT) was used for in vivo studies than that used for in vitro studies (i.e., 3.6 µT) to reduce the unwanted saturation caused by the MT effect . To correct B 0 inhomogeneity, WASSR‐based B 0 maps (acquisition time = 2.1 min) were acquired before and after CEST acquisition as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Dextran is a family of natural polysaccharides that have CEST MRI contrast originating from hydroxyl protons, enabling detection without the need for chemical modification with radioactive or metallic labels. Moreover, dextrans are polymers composed of tens to thousands of glucose units, providing a greatly boosted sensitivity for in vivo applications, such as imaging of prostate‐specific membrane antigen . Because dextrans are available in a variety of different molecular sizes, dexCEST MRI has the potential to characterize differential vascular permeability of tumors to particles in different size ranges .…”

Section: Introductionmentioning

confidence: 99%

CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans

Chen

Liu

et al. 2019

Magnetic Resonance in Med

Self Cite

View full text Add to dashboard Cite

Purpose Vascular disrupting therapy of cancer has become a promising approach not only to regress tumor growth directly but also to boost the delivery of chemotherapeutics in the tumor. An imaging approach to monitor the changes in tumor vascular permeability, therefore, has important applications for monitoring of vascular disrupting therapies. Methods Mice bearing CT26 subcutaneous colon tumors were injected intravenously with 150 kD dextran (Dex150, diameter, d~ 20 nm, 375 mg/kg), tumor necrosis factor‐alpha (TNF‐α; 1 µg per mouse), or both (n = 3 in each group). The Z‐spectra were acquired before and 2 h after the injection, and the chemical exchange saturation transfer (CEST) signals in the tumors as quantified by asymmetric magnetization transfer ratio (MTRasym) at 1 ppm were compared. Results The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTRasym = 0.042 ± 0.002) in the TNF‐α‐treated tumors than those by Dex150 alone (∆MTRasym = 0.000 ± 0.005, P = 0.0229) or TNF‐α alone (∆MTRasym = 0.002 ± 0.004, P = 0.0264), indicating that the TNF‐α treatment strongly augmented the tumor uptake of 150 kD dextran. The MRI findings were verified by fluorescence imaging and immunofluorescence microscopy. Conclusions High molecular weight dextrans can be used as safe and sensitive CEST MRI contrast agents for monitoring tumor response to vascular disrupting therapy and, potentially, for developing dextran‐based theranostic drug delivery systems.

show abstract

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

Cited by 61 publications

References 38 publications

Ratiometric NOE(−1.6) contrast in brain tumors

Ratiometric NOE(−1.6) contrast in brain tumors

Salicylic Acid‐Based Polymeric Contrast Agents for Molecular Magnetic Resonance Imaging of Prostate Cancer

CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans

Contact Info

Product

Resources

About