scholarly journals NIMG-70. A LABEL-FREE APPROACH TO ASSESS CHEMOTHERAPY DRUG CONCENTRATION USING CHEMICAL EXCHANGE SATURATION TRANSFER MRI – A FEASIBILITY STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi177-vi177
Author(s):  
David Kamson ◽  
Stuart Grossman ◽  
Zheng Han ◽  
Xiang Xu ◽  
Peter van Zijl ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Chemical Exchange ◽  
Detection Threshold ◽  
Chemical Exchange Saturation Transfer ◽  
High Dose ◽  
Label Free ◽  
Saturation Transfer ◽  
Synthetic Urine ◽  
Drug Concentrations ◽  
The Brain

Abstract BACKGROUND Drug delivery is one of the most pressing problems in neuro-oncology as the blood-brain barrier (BBB) uniquely limits penetration of substances into the brain parenchyma. Plasma and CSF drug concentrations are relatively easy to measure, but do not necessarily reflect concentrations in the brain. Furthermore, invasive measurements may be inaccurate in regions of heterogeneous BBB integrity. Advanced non-invasive imaging approaches may help bridge this information gap without the added risk. Chemical exchange saturation transfer (CEST) is an MRI technique that allows in vivo detection of molecules with a suitable hydrogen exchange rate, such as methotrexate (MTX). High-dose MTX is commonly used in oncology and its concentrations in urine (>2000µM), plasma (>1000µM) and enhancing brain tumors (>350µM) are well above the theoretical threshold of CEST. AIM: We aimed to confirm the CEST detectability of MTX in vitro, and to estimate the currently lowest measurable concentrations in solutions mimicking bodily fluids. METHODS We used a 9.4T MRI to assess the spectra of MTX at 37°C at various concentrations (0.1–10.0 mM) in a phosphate-buffered saline (PBS) solution at various pH (6.0–8.0), as well as in synthetic urine at pH 6.2. RESULTS CEST signals attributable to MTX at 1.5 and 2.7ppm were successfully detected in PBS at concentrations as low as 500µM. The optimal field strength was 3.6µT. While increasing pH increased the detection threshold of the 2.7ppm signal, the 1.5ppm signal was minimally affected by pH within physiologic ranges. In synthetic urine, the MTX CEST signal was well-detectable even at concentrations as low as 200µM. CONCLUSIONS These preliminary results suggest that MTX-CEST may be feasible at field strengths achievable in clinical scanners and at MTX concentrations previously measured in enhancing brain tumors treated with high-dose MTX. Further optimization of the technique for in human use is under way.

scholarly journals Chemical Exchange Saturation Transfer (CEST) MR Imaging for the Diagnosis of Brain Tumors

2020 ◽  
Author(s):  
Sachi OKUCHI ◽  
Yasutaka FUSHIMI ◽  
Tomohisa OKADA ◽  
Satoshi NAKAJIMA ◽  
Akihiko SAKATA ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Mr Imaging ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer

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

2021 ◽  
Author(s):  
Aditya N. Bade ◽  
Howard E. Gendelman ◽  
JoEllyn McMillan ◽  
Yutong Liu
Keyword(s):  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Antiretroviral Drugs ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Saturation Transfer ◽  
Viral Reservoirs ◽  
Drug Concentrations ◽  
Imaging Results ◽  
Magnetic Resonance Imaging Mri

AbstractHuman 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).MethodsCEST 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.ResultsCEST 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.ConclusionCEST 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.

scholarly journals Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood–brain barrier opening after intra-arterial infusion

2016 ◽  
Vol 36 (7) ◽  
pp. 1186-1194 ◽  
Author(s):  
Xiaolei Song ◽  
Piotr Walczak ◽  
Xiaowei He ◽  
Xing Yang ◽  
Monica Pearl ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Blood Brain Barrier ◽  
Chemical Exchange ◽  
Mri Contrast Agents ◽  
Brain Barrier ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Arterial Infusion ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated.

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