Cellular and Molecular Imaging Using Chemical Exchange Saturation Transfer

McMahon, Michael T.; Gilad, Assaf A.

doi:10.1097/rmr.0000000000000105

Cited by 12 publications

(12 citation statements)

References 117 publications

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“…, magnetization transfer). 7 By this method, Oskolkov and coworkers observed MR contrast from 733 μM human protamine-1, an arginine-rich nuclear protein that was sensitive to pH, phosphorylation state, nucleotides, and heparin. 8 Notably, the low sensitivity of 1 H MRI has limited the development of GE T 1 , T 2 , and 1 H-CEST contrast agents for molecular imaging.…”

Section: Introductionmentioning

confidence: 99%

Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent

2017

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Section: Introductionmentioning

confidence: 99%

Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent

2017

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“…It has to be considered that Z ‐spectra of YbHPDO3A in vivo can be influenced by the magnetization transfer contrast (MTC) provided by immobilized proteins of tissues . This can affect the ST% of SAP and TSAP CEST peaks.…”

Section: Resultsmentioning

confidence: 99%

“…It has to be considered that Z-spectra of YbHPDO3A in vivo can be influenced by the magnetization transfer contrast (MTC) provided by immobilized proteins of tissues. [25][26][27][28] This can affect the ST% of SAP and TSAP CEST peaks. Therefore, in vitro pH-variable calibration curves of YbHPDO3A have been also recorded in the presence of serum albumin immobilized by heating ( Figure 1F).…”

Section: Discussionmentioning

confidence: 99%

“…An important step forward has been taken with the introduction of chemical exchange saturation transfer (CEST) agents [25][26][27][28] endowed with at least two NMR-distinguishable sets of exchangeable protons with different pH responsivenesses. The MRI contrast of these probes can be analyzed by using a ratiometric approach, thanks to which pHe can be assessed independently of knowing the actual probe concentration.…”

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confidence: 99%

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CEST‐MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry

et al. 2018

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In glioma, the acidification of the extracellular tumor microenvironment drives proliferation, angiogenesis, immunosuppression, invasion and chemoresistance. Therefore, quantification of glioma extracellular pH (pHe) is of crucial importance. This study is focused on the application of the YbHPDO3A (ytterbium 1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane) probe for in vivo glioma pHe quantification using chemical exchange saturation transfer (CEST)-MRI and its correlation with tumor metabolism assessed by immunohistochemistry. The U87 glioma mouse model was used (n = 18) and MRI performed at 4.7 T. CEST-MRI of YbHPDO3A solutions at different pH values showed two resolved CEST spectra at 71 ppm and 99 ppm, both sensitive to pH variations, allowing therefore calculation of the ratiometric curve for in vivo pH quantification. In vivo MRI sequences consisted of T for tumor localization, T * to assess YbHPDO3A biodistribution by exploiting its magnetic susceptibility effect and CEST for glioma pHe mapping. T * images show that YbHPDO3A extravasates in tumor in regions with damaged blood-brain barrier. The pHe is calculated only in these regions. Hematoxylin/eosin histology and Ki-67, CA-IX (carbonic anhydrase 9) and NHE-1 immunohistochemical staining were performed; their expression rates were compared with the in vivo pHe values. On the basis of the cell proliferation marker Ki-67, two groups were defined: one group with a lower mitotic index (MI% < 20% = mean value) and a mean pHe value of 7.00 (low-proliferation/high-pH group) and the other with MI% > 20% and an acidic pHe of 6.6 (high-proliferation/low-pH group). CA-IX and NHE-1 were over-expressed in the high-proliferation/low-pH group (CA-IX, 92 ± 7% versus 30 ± 13%; NHE-1, 84 ± 8% versus 35 ± 11%), indicating an acidic/hypoxic microenvironment. These immunohistochemical results are consistent with our pHe mapping (Pearson correlation coefficient > 0.70) and provide evidence for the feasibility of the CEST-MRI method with the YbHPDO3A probe for glioma pHe quantification at 4.7 T. Importantly, the YbHPDO3A probe has similar chemical and biological properties to the clinically approved MRI contrast agent GdHPDO3A. This makes the method promising for a clinical translation.

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“…It arises when an exchangeable proton of a macromolecule is magnetically saturated and transferred to water by chemical exchange causing water MRI signal reduction that reflects macromolecule concentrations. Continuous proton exchanges between the macromolecule and water leading to the buildup of the signal reduction, and the large number of molecules in tissue amplify detection [16][17][18][19][20]. Compared to traditional drug detection systems that tag medicines with an imaging agent or load drugs and imaging agents into a nanoparticle, CEST-based imaging does not require extrinsic drug detection agents.…”

Section: Introductionmentioning

confidence: 99%

Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue

Bade

Gendelman

McMillan

et al. 2021

Preprint

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Human immunodeficiency virus type-1 (HIV-1) antiretroviral drug (ARV) theranostics facilitates biodistribution and efficacy of therapies designed to target viral reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrast to detect ARV distribution within the central nervous system (CNS). Methods: CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses in solutions. CEST magnetic resonance imaging (MRI) was performed on 3TC-treated mice with analysis made by Lorentzian fitting. Results: CEST effects of 3TC and FTC hydroxyl and amino protons linearly correlated to drug concentrations. 3TC was successfully detected in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations. Conclusion: CEST contrasts can be used to detect ARVs using MRI. Such detection can be used to assess spatial-temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity.

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Cellular and Molecular Imaging Using Chemical Exchange Saturation Transfer

Cited by 12 publications

References 117 publications

Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent

Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent

CEST‐MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry

Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue

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Cellular and Molecular Imaging Using Chemical Exchange Saturation Transfer

Cited by 12 publications

References 117 publications

Nanomolar small-molecule detection using a genetically encoded129Xe NMR contrast agent

Nanomolar small-molecule detection using a genetically encoded129Xe NMR contrast agent

CEST‐MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry

Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue

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Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent

Nanomolar small-molecule detection using a genetically encoded¹²⁹Xe NMR contrast agent