3 results on '"AACID"'
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2. Brain pH Measurement Using AACID CEST MRI Incorporating the 2 ppm Amine Resonance
- Author
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Mohammed Albatany, Susan Meakin, and Robert Bartha
- Subjects
Brain pH ,AACID ,CEST MRI ,2 ppm amine resonance ,cancer ,glioblastoma multiforme ,Brain ,Hydrogen-Ion Concentration ,Glioblastoma multiforme ,Amides ,Magnetic Resonance Imaging ,Mice ,Animals ,Radiology, Nuclear Medicine and imaging ,Amines ,Cancer - Abstract
Many pathological conditions lead to altered intracellular pH (pHi) disrupting normal cellular functions. The chemical exchange saturation transfer (CEST) method, known as Amine and Amide Concentration Independent Detection (AACID), can produce image contrast that is predominantly dependent on tissue intracellular pHi. The AACID value is linearly related to the ratio of the 3.5 ppm amide CEST effect and the 2.75 ppm amine CEST effect in the physiological range. However, the amine CEST effect at 2 ppm is often more clearly defined in vivo, and may provide greater sensitivity to pH changes. The purpose of the current study was to compare AACID measurement precision utilizing the 2.0 and 2.75 ppm amine CEST effects. We hypothesized that the 2.0 ppm amine CEST resonance would produce measurements with greater sensitivity to pH changes. In the current study, we compare the range of the AACID values obtained in 24 mice with brain tumors and in normal tissue using the 2 ppm and 2.75 ppm amine resonances. All CEST data were acquired on a 9.4T MRI scanner. The AACID measurement range increased by 39% when using the 2 ppm amine resonance compared to the 2.75 ppm resonance, with decreased measurement variability across the brain. These data indicate that in vivo pH measurements made using AACID CEST can be enhanced by incorporating the 2 ppm amine resonance. This approach should be considered for pH measurements made over short intervals when no changes are expected in the concentration of metabolites that contribute to the 2 ppm amine resonance.
- Published
- 2022
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3. Topiramate induces acute intracellular acidification in glioblastoma
- Author
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Alex X. Li, Miranda Bellyou, Susan O. Meakin, Kamini Marathe, Robert Bartha, and Nevin McVicar
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,Chemical exchange saturation transfer ,Intracellular Space ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Carbonic anhydrase inhibitor ,Carbonic Anhydrases ,Tumor ,biology ,Brain Neoplasms ,Lonidamine ,Forkhead Transcription Factors ,Hydrogen-Ion Concentration ,Magnetic Resonance Imaging ,3. Good health ,Intracellular pH ,Neuroprotective Agents ,Neurology ,Oncology ,030220 oncology & carcinogenesis ,AACID ,CEST ,Intracellular ,medicine.drug ,Topiramate ,medicine.medical_specialty ,medicine.drug_class ,Mice, Nude ,Fructose ,03 medical and health sciences ,Magnetic resonance imaging ,Carbonic anhydrase ,Cell Line, Tumor ,medicine ,Extracellular ,Animals ,Humans ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,biology.protein ,Cancer research ,Neurology (clinical) ,Glioblastoma - Abstract
Reversal of the intracellular/extracellular pH gradient is a hallmark of malignant tumors and is an important consideration in evaluating tumor growth potential and the effectiveness of anticancer therapies. Glioblastoma multiforme (GBM) brain tumors have increased expression of the carbonic anhydrase (CA) isozymes CAII, CAIX and CAXII that contribute to the altered regulation of intracellular pH (pHi). The anti-epileptic drug topiramate (TPM) inhibits CA action and may acidify the tumor intracellular compartment. In-vivo detection of acute tumor acidification could aid in cancer diagnosis and monitoring treatment response. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has been used to measure tissue pH. Using a recently developed CEST-MRI method called amine/amide concentration independent detection (AACID), we have previously shown intracellular acidification caused by single dose of lonidamine. The current study aims to evaluate the intracellular acidification induced by a single dose of the clinically approved drug TPM. Brain tumors were induced in NU/NU mice by injecting 105 U87 human glioblastoma multiforme cells into the right frontal lobe. Using a 9.4T MRI scanner AACID measurements were acquired, before and after administration of TPM (dose: 120 mg/kg, intraperitoneal), 15 ± 2 days after tumor cell implantation. TPM administration induced acute intracellular acidification (average ± SD: baseline AACID = 1.14 ± 0.05; post AACID = 1.19 ± 0.05, paired ttest p = 0.02) in implanted brain tumors. In contrast, contralateral tissue showed no change in AACID value. These results suggest that topiramate can rapidly induce a tumor specific physiological change detectable by AACID CEST. This pH challenge paradigm could be exploited to aid in tumor detection and monitoring treatment response.
- Published
- 2016
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