scholarly journals FSMP-06. IN VIVO MONITORING OF LDHA EXPRESSION IN GLIOBLASTOMA USING QUANTITATIVE EXCHANGED-LABEL TURNOVER 1H MRS TECHNIQUE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Puneet Bagga ◽  
Laurie Rich ◽  
Mohammad Haris ◽  
Neil Wilson ◽  
Mitch Schnall ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Lactate Production ◽  
Deuterium Labeling ◽  
1H Mrs ◽  
In Vivo Monitoring ◽  
Lactate Turnover ◽  
Crucial Information ◽  
Specialized Hardware

Abstract Most cancers, including glioblastomas (GBMs), rely extensively on glycolysis to support growth, proliferation, and survival. A hallmark of this elevated glycolysis is overexpression of Lactate dehydrogenase-A (LDHA) protein leading to increased uptake of glucose and overproduction of lactate. Various clinical trials using LDHA as a target for diagnosis and treatment have yielded encouraging results. However, in vivo monitoring of LDHA expression has been challenging due to either requirement of administration of radioactive substrates or specialized hardware. In this presentation, we will demonstrate a new method-quantitative exchanged-label turnover MRS (QELT, or simply qMRS)-that increases the sensitivity of magnetic resonance-based metabolic mapping without the requirement for specialized hardware. qMRS relies on the administration of deuterated (2H-labeled) substrates to track the production of downstream metabolites. Since 2H is invisible on 1H MRS, replacement of 1H with 2H due to metabolic turnover leads to an overall reduction in 1H MRS signal for the corresponding metabolites. We applied our qMRS technique to monitor the rate of lactate production in a preclinical GBM model. Infusion of [6,6’-2H2]glucose led to downstream deuterium labeling of lactate, thereby resulting in a reduction in the 1.33 ppm lactate-CH3 peak on 1H MRS over time. The subtraction of post-administration 1H MR spectra from the pre-infusion spectra aided in the determination of the kinetics of the lactate turnover. We believe that the detection and quantification of lactate production kinetics may provide crucial information regarding tumor LDHA expression non-invasively in GBMs without requiring biopsies. Hence, qMRS is expected to open up new opportunities to probe LDHA expression differences in a variety of gliomas, including GBMs and astrocytomas. This method takes advantage of the universal availability and ease of implementation of 1H MRS on all clinical and preclinical magnetic resonance scanners.

scholarly journals BIMG-08. DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY USING 2H-PYRUVATE ALLOWS NON-INVASIVE IN VIVO IMAGING OF TERT EXPRESSION IN BRAIN TUMORS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
In Vivo Imaging ◽  
Lactate Production ◽  
Telomere Maintenance ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Non Invasive ◽  
Tert Expression

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.

scholarly journals 81 IN VIVO PROTON MAGNETIC RESONANCE SPECTROSCOPY (1H-MRS) IN CYSTIC LEUCOMALACIA OF INFANCY

1994 ◽  
Vol 36 (1) ◽  
pp. 16A-16A
Author(s):  
Floris Groenendaal ◽  
Paula Eken ◽  
Jeroen Van Der Grond ◽  
Karin Rademaker ◽  
Linda S De Vries
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
1H Mrs

BIOM-10. PRECLINICAL PLATFORM FOR THE IDENTIFICATION OF DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY-BASED BIOMARKERS OF BRAIN TUMOR METABOLISM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Georgios Batsios ◽  
Meryssa Tran ◽  
Céline Taglang ◽  
Anne Marie Gillespie ◽  
Sabrina Ronen ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Tumors ◽  
Treatment Response ◽  
Lactate Production ◽  
Cell Suspensions ◽  
Response To Therapy ◽  
Resonance Spectroscopy

Abstract Metabolic reprogramming is a fundamental hallmark of cancer, which can be exploited for non-invasive tumor imaging. Deuterium magnetic resonance spectroscopy (2H-MRS) recently emerged as a novel, translational method of interrogating flux from 2H-labeled substrates to metabolic products. However, to date, preclinical studies have been performed in vivo, an endeavor which suffers from low-throughput and potential wastage of animal life, especially when considering studies of treatment response. Developing in vitro assays for monitoring metabolism of 2H-labeled substrates will enhance throughput, lead to the rapid evaluation of new 2H-based probes and enable identification of treatment response biomarkers, thereby allowing the best 2H-based probes to be translated for further in vivo assessment. The goal of this study was to develop a preclinical cell-based platform for quantifying metabolism of 2H-labeled probes in brain tumor models. Since the Warburg effect, which is characterized by elevated glycolytic production of lactate, is a metabolic phenotype of cancer, including brain tumors, we examined metabolism of 2H-glucose or 2H-pyruvate in patient-derived glioblastoma (GBM6) and oligodendroglioma (BT88) cells and compared to normal human astrocytes (NHACONTROL). Following incubation in media containing [6,6’-2H]glucose or [U-2H]pyruvate, 2H-MR spectra obtained from live cell suspensions showed elevated 2H-lactate production in GBM6 and BT88 cells relative to NHACONTROL. Importantly, 2H-lactate production from [6,6’-2H]glucose or from [U-2H]pyruvate was reduced in GBM6 or BT88 cells subjected to irradiation and temozolomide, which is standard of care for glioma patients, pointing to the utility of this method for detecting response to therapy. Collectively, we have, for the first time, demonstrated the ability to quantify metabolism of 2H-MRS probes in live cell suspensions and validated the utility of our assay for differentiating tumor from normal cells and assessing response to therapy. Our studies will expedite the identification of novel 2H-MRS probes for imaging brain tumors and potentially other types of cancer.

scholarly journals Development of a Mouse Glioblastoma Orthotopic Model Using the GLi-261 Cell Line

2019 ◽  
Vol 19 (4) ◽  
pp. 242-250
Author(s):  
A. A. Borzov ◽  
A. A. Оvsepyan ◽  
E. I. Katorkina ◽  
E. O. Anisimova ◽  
M. V. Lykov
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Neurological Status ◽  
Tumour Volume ◽  
Test System ◽  
Experimental Models ◽  
Orthotopic Model ◽  
In Vivo Test

Glioblastoma is the most common and most aggressive type of brain tumor, with an almost 100 % mortality rate over 5 years. The search for new effective approaches to the treatment of this disease requires the development of adequate experimental models.Objective: to develop and put into practice an orthotopic model of mouse glioblastoma.Materials and methods: GLi-261 mouse glioma cells were orthotopically inoculated into the putamen of C57Bl/6 mice brain. Tumor dynamics was investigated by Preclinical MRI System 7.0T/17cm (Flexiscan) highfield magnetic resonance imager (MR Solutions, UK). Temcital® (temozolomide) was used as a positive control in the treatment of experimental glioblastoma. The neurological status of animals in the course of tumour development was assessed by specific tests.Results: a GLi-261 cell-based mouse glioblastoma orthotopic model was developed using stereotactic equipment for accurate inoculation of tumour cells, magnetic resonance imaging for non-invasive determination of tumour volume and dynamics, and special tests for determination of the neurological status of the biological test systems. This model was used to demonstrate the effectiveness of temozolomide (the «gold standard» for glioblastoma treatment).Conclusions: this model has been introduced into practice at the IBC Generium, LLC, and can be used as an in vivo test system for preclinical evaluation of efficacy of new antitumour drugs being developed, as well as brain cancer treatment regimens using combination therapy.

scholarly journals In Vivo Monitoring of Inflammation After Cardiac and Cerebral Ischemia by Fluorine Magnetic Resonance Imaging

Circulation ◽  
2008 ◽  
Vol 118 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Ulrich Flögel ◽  
Zhaoping Ding ◽  
Hendrik Hardung ◽  
Sebastian Jander ◽  
Gaby Reichmann ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebral Ischemia ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
In Vivo Monitoring ◽  
Fluorine Magnetic Resonance Imaging

Determination of In-Vivo Elastic Properties of Soft Tissue Using Magnetic Resonance Elastography

2003 ◽  
Author(s):  
Francis E. Kennedy ◽  
Marvin M. Doyley ◽  
Elijah E. W. Van Houten ◽  
John B. Weaver ◽  
Keith D. Paulsen
Keyword(s):  
Magnetic Resonance ◽  
Soft Tissue ◽  
Elastic Properties ◽  
Magnetic Resonance Elastography ◽  
Tissue Properties ◽  
In Vivo Measurement ◽  
Ultrasonic Methods ◽  
Accurate Quantification

In-vivo measurement of the elastic properties of soft tissue have been made using a variety of direct techniques, such as indentation probes and rotary shear actuators, but they are unable to access much of the soft tissue of interest. Indirect ultrasonic methods for imaging elastic properties of soft tissue were first introduced about 15 years ago, see Ophir (1991). Although the results of ultrasonic elastography studies have been quite promising, they may not be suited for applications requiring accurate quantification of soft tissue properties. An alternative to ultrasound, magnetic resonance imaging, has the advantage of enabling precise measurement of all three components of tissue displacement. The reconstruction of elastic properties from the imaged displacement field is called magnetic resonance elastography (MRE), and is the subject of this paper.

Sign in / Sign up

Export Citation Format

Share Document