25 results on '"Kim Halbert"'
Search Results
2. Supplementary Table S2 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
[18F]DASA-23 administered activity in brain tumor patients
- Published
- 2023
3. Supplementary Figure S8 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Imaging of IC-2
- Published
- 2023
4. Data from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Purpose:Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM.Experimental Design:[18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma.Results:In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation.Conclusions:We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.
- Published
- 2023
5. Supplementary Table S5 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Hematology laboratory testing results of patients imaged with [18F]DASA-23
- Published
- 2023
6. Supplementary Figure S10 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Imaging of IC-4
- Published
- 2023
7. Supplementary Figure S1 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
[18F]DASA-23 Radiosynthesis
- Published
- 2023
8. Supplementary Figure S3 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Evaluation of PKM2 expression in U87-GFP/luc orthotopic GBM
- Published
- 2023
9. Supplementary Table S4 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Vital signs of the patients administered with [18F]DASA-23
- Published
- 2023
10. Supplementary Figure S2 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Comparative metabolic PET/CT imaging in U87-GFP/luc GBM mice
- Published
- 2023
11. Supplementary Figure S7 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
PKM2 analysis in TP459 neurospheres
- Published
- 2023
12. Supplementary Figure S4 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
[18F]DASA-23 time activity curves
- Published
- 2023
13. Supplementary Table S1 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
[18F]DASA-23 administered activity in healthy volunteers
- Published
- 2023
14. Supplementary Figure S9 from A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Sanjiv Sam Gambhir, Lawrence D. Recht, Seema Nagpal, Reena Thomas, Guido Davidzon, Andrei Iagaru, Tarik F. Massoud, Mehdi Khalighi, Melanie Hayden-Gephart, Irving Weissman, Geoffrey I. Warnock, Donald E. Born, Pauline Chu, Rahul Sinha, Nobuko Uchida, Daniel Dan Liu, Eli Johnson, Monica Granucci, Joy Q. He, Harsh Gandhi, Kim Halbert, Dawn Holley, Michelle L. James, Israt S. Alam, Mary Ellen I. Koran, Jun Hyung Park, Bin Shen, Pablo Buccino, Megan Phillips, Samantha T. Reyes, Jessa B. Castillo, Lewis Naya, Surya Murty, Tom Haywood, Chirag B. Patel, and Corinne Beinat
- Abstract
Imaging of IC-3
- Published
- 2023
15. A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
- Author
-
Israt S. Alam, Nobuko Uchida, Pauline Chu, Lewis Naya, Melanie Hayden-Gephart, Corinne Beinat, Guido Davidzon, Jessa B. Castillo, Mary Ellen I. Koran, Andrei Iagaru, Geoffrey I. Warnock, Harsh Gandhi, Donald E. Born, Samantha T. Reyes, Jun Hyung Park, Kim Halbert, Michelle L. James, Lawrence Recht, Irving L. Weissman, Dawn Holley, Pablo Buccino, Monica Granucci, Bin Shen, Eli Johnson, Rahul Sinha, Sanjiv S. Gambhir, Daniel Dan Liu, Seema Nagpal, Megan Phillips, Tom Haywood, Mehdi Khalighi, Reena Thomas, Chirag B. Patel, Surya Murty, Tarik F. Massoud, and Joy Q He
- Subjects
Cancer Research ,medicine.diagnostic_test ,Chemistry ,Magnetic resonance imaging ,PKM2 ,medicine.disease ,Oncology ,Positron emission tomography ,Cell culture ,Glioma ,medicine ,Cancer research ,Glycolysis ,U87 ,Pyruvate kinase - Abstract
Purpose: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. Experimental Design: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. Results: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. Conclusions: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.
- Published
- 2021
16. True ultra-low-dose amyloid PET/MRI enhanced with deep learning for clinical interpretation
- Author
-
Kim Halbert, Athanasia Boumis, Harsh Gandhi, Dawn Holley, Kevin Chen, Tyler N. Toueg, Mehdi Khalighi, Greg Zaharchuk, Michael Zeineh, Mary Ellen I. Koran, Guido Davidzon, Gabriel Kennedy, and Elizabeth C. Mormino
- Subjects
Image quality ,Coefficient of variation ,Image processing ,Standardized uptake value ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Deep Learning ,0302 clinical medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Reproducibility ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,General Medicine ,Magnetic Resonance Imaging ,Signal-to-noise ratio (imaging) ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Tomography ,Tomography, X-Ray Computed ,Nuclear medicine ,business ,Emission computed tomography - Abstract
PURPOSE: While sampled or short-frame realizations have shown the potential power of deep learning to reduce radiation dose for PET images, evidence in true injected ultra-low-dose cases is lacking. Therefore, we evaluated deep learning enhancement using a significantly reduced injected radiotracer protocol for amyloid PET/MRI. METHODS: Eighteen participants underwent two separate (18)F-florbetaben PET/MRI studies in which an ultra-low-dose (6.64 ± 3.57 MBq, 2.2 ± 1.3% of standard) or a standard-dose (300 ± 14 MBq) was injected. The PET counts from the standard-dose list-mode data were also undersampled to approximate an ultra-low-dose session. A pre-trained convolutional neural network was fine-tuned using MR images and either the injected or sampled ultra-low-dose PET as inputs. Image quality of the enhanced images was evaluated using three metrics (peak signal-to-noise ratio, structural similarity, and root mean square error), as well as the coefficient of variation (CV) for regional standard uptake value ratios (SUVRs). Mean cerebral uptake was correlated across image types to assess the validity of the sampled realizations. To judge clinical performance, four trained readers scored image quality on a five-point scale (using 15% non-inferiority limits for proportion of studies rated 3 or better) and classified cases into amyloid-positive and negative studies. RESULTS: The deep learning–enhanced PET images showed marked improvement on all quality metrics compared with the low-dose images as well as having generally similar regional CVs as the standard-dose. All enhanced images were non-inferior to their standard-dose counterparts. Accuracy for amyloid status was high (97.2% and 91.7% for images enhanced from injected and sampled ultra-low-dose data, respectively) which was similar to intra-reader reproducibility of standard-dose images (98.6%). CONCLUSION: Deep learning methods can synthesize diagnostic-quality PET images from ultra-low injected dose simultaneous PET/MRI data, demonstrating the general validity of sampled realizations and the potential to reduce dose significantly for amyloid imaging.
- Published
- 2021
17. Cerebrovascular reactivity measurements using simultaneous 15O-water PET and ASL MRI: Impacts of arterial transit time, labeling efficiency, and hematocrit
- Author
-
Yosuke Ishii, Magdalena Sokolska, Audrey P. Fan, Bin Shen, Jia Guo, Andrea Otte, Moss Y. Zhao, Mohammad Mehdi Khalighi, David Yen Ting Chen, Taghi Rostami, Jun Hyung Park, Dawn Holley, Greg Zaharchuk, David D. Shin, Kim Halbert, and Brittney Williams
- Subjects
Male ,Time Factors ,Hematocrit ,Medical and Health Sciences ,0302 clinical medicine ,Oxygen Radioisotopes ,Cerebrovascular reactivity ,screening and diagnosis ,medicine.diagnostic_test ,05 social sciences ,Brain ,Middle Aged ,Cerebral blood flow ,Detection ,Neurology ,Positron emission tomography ,Cerebrovascular Circulation ,Cardiology ,Biomedical Imaging ,Female ,Velocity selective arterial spin labeling ,Acetazolamide ,Blood Flow Velocity ,medicine.drug ,RC321-571 ,4.2 Evaluation of markers and technologies ,MRI ,Adult ,medicine.medical_specialty ,Cognitive Neuroscience ,Transit time ,Neurosciences. Biological psychiatry. Neuropsychiatry ,050105 experimental psychology ,03 medical and health sciences ,Magnetic resonance imaging ,Clinical Research ,Internal medicine ,medicine ,otorhinolaryngologic diseases ,Humans ,0501 psychology and cognitive sciences ,Aged ,Cerebrovascular reserve ,Neurology & Neurosurgery ,business.industry ,Psychology and Cognitive Sciences ,Neurosciences ,Water ,Gold standard (test) ,Cerebrovascular Disorders ,PET/MRI ,PET ,Positron-Emission Tomography ,Spin Labels ,business ,Pseudo-continuous arterial spin labeling ,030217 neurology & neurosurgery - Abstract
Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain=42±19% and 40±18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15±10% compared with PET (p
- Published
- 2021
18. A Clinical PET Imaging Tracer ([
- Author
-
Corinne, Beinat, Chirag B, Patel, Tom, Haywood, Surya, Murty, Lewis, Naya, Jessa B, Castillo, Samantha T, Reyes, Megan, Phillips, Pablo, Buccino, Bin, Shen, Jun Hyung, Park, Mary Ellen I, Koran, Israt S, Alam, Michelle L, James, Dawn, Holley, Kim, Halbert, Harsh, Gandhi, Joy Q, He, Monica, Granucci, Eli, Johnson, Daniel Dan, Liu, Nobuko, Uchida, Rahul, Sinha, Pauline, Chu, Donald E, Born, Geoffrey I, Warnock, Irving, Weissman, Melanie, Hayden-Gephart, Mehdi, Khalighi, Tarik F, Massoud, Andrei, Iagaru, Guido, Davidzon, Reena, Thomas, Seema, Nagpal, Lawrence D, Recht, and Sanjiv Sam, Gambhir
- Subjects
Mice ,Brain Neoplasms ,Positron-Emission Tomography ,Pyruvate Kinase ,Sulfanilic Acids ,Animals ,Humans ,Diazonium Compounds ,Glioblastoma ,Glycolysis ,Article - Abstract
PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[(18)F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([(18)F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients. EXPERIMENTAL DESIGN: [(18)F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [(18)F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [(18)F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers, and a pilot cohort of glioma patients. RESULTS: In mouse imaging studies, [(18)F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 ± 0.5. In human volunteers, [(18)F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [(18)F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [(18)F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it identified a metabolic non-responder within 1-week of treatment initiation. CONCLUSION: We developed and translated [(18)F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [(18)F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.
- Published
- 2021
19. Cerebrovascular reactivity measurements using simultaneous
- Author
-
Moss Y, Zhao, Audrey P, Fan, David Yen-Ting, Chen, Magdalena J, Sokolska, Jia, Guo, Yosuke, Ishii, David D, Shin, Mohammad Mehdi, Khalighi, Dawn, Holley, Kim, Halbert, Andrea, Otte, Brittney, Williams, Taghi, Rostami, Jun-Hyung, Park, Bin, Shen, and Greg, Zaharchuk
- Subjects
Adult ,Male ,Positron emission tomography ,Time Factors ,Article ,Magnetic resonance imaging ,Oxygen Radioisotopes ,otorhinolaryngologic diseases ,Humans ,Cerebrovascular reactivity ,Aged ,Cerebrovascular reserve ,Brain ,Water ,Middle Aged ,Cerebral blood flow ,Cerebrovascular Disorders ,PET/MRI ,Hematocrit ,Cerebrovascular Circulation ,Positron-Emission Tomography ,Female ,Spin Labels ,Velocity selective arterial spin labeling ,Pseudo-continuous arterial spin labeling ,Blood Flow Velocity - Abstract
Cerebrovascular reactivity (CVR) reflects the capacity of the brain to meet changing physiological demands and can predict the risk of cerebrovascular diseases. CVR can be obtained by measuring the change in cerebral blood flow (CBF) during a brain stress test where CBF is altered by a vasodilator such as acetazolamide. Although the gold standard to quantify CBF is PET imaging, the procedure is invasive and inaccessible to most patients. Arterial spin labeling (ASL) is a non-invasive and quantitative MRI method to measure CBF, and a consensus guideline has been published for the clinical application of ASL. Despite single post labeling delay (PLD) pseudo-continuous ASL (PCASL) being the recommended ASL technique for CBF quantification, it is sensitive to variations to the arterial transit time (ATT) and labeling efficiency induced by the vasodilator in CVR studies. Multi-PLD ASL controls for the changes in ATT, and velocity selective ASL is in theory insensitive to both ATT and labeling efficiency. Here we investigate CVR using simultaneous 15O-water PET and ASL MRI data from 19 healthy subjects. CVR and CBF measured by the ASL techniques were compared using PET as the reference technique. The impacts of blood T1 and labeling efficiency on ASL were assessed using individual measurements of hematocrit and flow velocity data of the carotid and vertebral arteries measured using phase-contrast MRI. We found that multi-PLD PCASL is the ASL technique most consistent with PET for CVR quantification (group mean CVR of the whole brain = 42 ± 19% and 40 ± 18% respectively). Single-PLD ASL underestimated the CVR of the whole brain significantly by 15 ± 10% compared with PET (p
- Published
- 2020
20. Dioxin and furan contamination of deodorizer distillates and natural vitamin E supplements
- Author
-
Jeffrey C. Archer and Mary Kim Halbert
- Subjects
Chromatography ,Vitamin E ,medicine.medical_treatment ,Extraction (chemistry) ,Vitamin E supplement ,Contamination ,law.invention ,chemistry.chemical_compound ,Congener ,chemistry ,law ,Furan ,medicine ,Tocopherol ,Distillation ,Food Science - Abstract
Thirty-five samples of vitamin E supplement softgels, obtained from store shelves, were analyzed for 17 dioxin and furan congeners. Of these samples, 14 were identified as natural vitamin E, containing D- α -tocopherol, as well as lesser amounts of β -, α -, and δ -tocopherols, and the remaining 21 were labeled as synthetic vitamin E, containing a mixture of D- and L- α -tocopherol. The supplements were collected during the years of 2002 and 2004. The seven natural vitamin E supplements collected in 2002 were found to contain significant quantities of dioxins and furans, with an average total toxic equivalence (TEQ) of 0.79 pg/g, compared to 0.10 g/g for the 2004 natural vitamin E supplements. The 21 synthetic vitamin E supplements collected during the same time period showed little or no contamination, with an average TEQ of 0.057 pg/g. Eight samples of deodorizer distillate, from which natural vitamin E is derived, were also collected and analyzed. The distillates exhibit an overall congener pattern similar to that found in the natural vitamin E, but at a much higher average TEQ of 3.4 pg/g. This suggests the possibility of carryover of contamination to the vitamin E samples from the deodorizer distillate during the extraction process. The natural vitamin E supplements collected in 2004 have much lower levels of contamination, suggesting that improved extraction processes may be in use, effectively reducing contamination.
- Published
- 2007
21. Modeling and assaying dioxin-like biological effects for both dioxin-like and certain non-dioxin-like compounds
- Author
-
Jon G. Wilkes, Ralph L. Kodell, Lisa Jennings, Jeffrey C. Archer, Richard D. Beger, Laura K. Schnackenberg, Lisa Pence, Mary Kim Halbert, Dan A. Buzatu, and Bruce S. Hass
- Subjects
Quantitative structure–activity relationship ,Magnetic Resonance Spectroscopy ,In silico ,Quantitative Structure-Activity Relationship ,Toxicology ,Dioxins ,Transfection ,Models, Biological ,Risk Assessment ,Cell Line ,Mice ,Genes, Reporter ,Toxicity Tests ,Bioassay ,Animals ,Humans ,Relative potency ,Luciferase Gene ,Furans ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Reproducibility of Results ,Polychlorinated Biphenyls ,Biochemistry ,Gene Expression Regulation ,Liver ,Receptors, Aryl Hydrocarbon ,Environmental chemistry ,Toxicity ,Biological Assay ,Environmental Pollutants ,Non dioxin like ,Applicability domain - Abstract
13C NMR data have been correlated to Toxic Equivalency Factors (TEFs) of the 29 PCDDs, PCDFs, or PCBs for which non-zero TEFs have been defined. Such correlations are called quantitative spectrometric data-activity relationship (QSDAR) models. An improved QSDAR model predicted TEFs of 0.037 and 0.004, respectively, for 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD), both among the 390 congeners for which zero value TEFs are assumed. A QSDAR model of Relative Potency (REP) values estimated the corresponding values as 0.115 and 0.020. Results from both models indicated that these two congeners may exhibit significant dioxin-like toxicity. If other such congeners have non-zero toxicity, TEF-based risk assessments of some dioxin-, furan-, or PCB-contaminated sites or foods may underestimate toxicity. Both models were extensively cross-validated and the TEF model was externally validated. We confirmed the predictions by an independent in vitro method, a luciferase gene expression assay based on mouse liver cells that found REPs of 0.027 and 0.013, respectively, for 1,3,7,8-TCDD and 1,2,3,4,7-PeCDD. The QSDAR-estimated and gene-expression assayed values agreed. The models were used to predict activity for an applicability domain including 108 non-2,3,7,8 dioxin, furan, or PCB congeners and 2,3,7,8-tetrachlorophenothiazine, a dioxin analog proposed as a drug candidate. This study showed that QSDAR prediction followed by a relatively inexpensive in vitro assay could be used to nominate a few candidates among hundreds for further investigation. It suggested that in silico and in vitro nomination protocols may facilitate practical risk assessment when chemical family members exhibit different degrees of toxicity operating via a common mechanism.
- Published
- 2007
22. A Method for Detection of Untapped Intervals in a Complex Lithology System
- Author
-
Iraj Ershaghi, Anthony Taglieri, Kim Halbert, and Abdassah Doddy
- Subjects
Lithology ,Geochemistry ,Mineralogy ,Geology - Abstract
This paper is a case study calibrating well log derived lithology indicators with productivity attributes from modern production logs. More than thirty wells drilled thirty years ago into the South Ellwood Field were completed based on limited understanding of the well log responses in the complex Monterey Formation. From a retrospective study of well productivity, Wylie, Ershaghi and Christensen1 presented a pattern recognition technique for identifying productive intervals. Availability of recently obtained state-of-the-art production logs has provided invaluable information about the relevance of the well log derived potential zones to positively tested productive and undamaged intervals. This paper includes an analysis of the information processing from the Flow View and Gas Holdup Sensor Tool. A calibration of production log data and well log lithology pattern studies is the basis of designing a re-development strategy for untapped intervals not perforated in the initial completion work. Furthermore, the calibration methodology is extended to a nearby field with similar geology for reassessment of reserves potential.
- Published
- 2002
23. Determination of lidocaine and active metabolites in blood serum by liquid chromatography with electrochemical detection
- Author
-
Richard P. Baldwin and Mary Kim Halbert
- Subjects
Detection limit ,Time Factors ,Chromatography ,Lidocaine ,Chemistry ,General Chemistry ,Electrochemical detection ,Glassy carbon ,Bupivacaine ,Blood serum ,Glycine ,Electrochemistry ,medicine ,Humans ,Active metabolite ,Chromatography, Liquid ,medicine.drug - Abstract
Oxidation of lidocaine and its principal metabolites, monoethylglycine xylidide and glycine xylidide, at glassy carbon electrodes was employed to permit electrochemical detection of these compounds following separation by high-performance liquid chromatography. The absolute detection limits found for these compounds were 2 ng, 5 ng, and 4 ng injected, respectively. The resulting assay was suitable for the routine quantitation of lidocaine and these metabolites in blood serum over the entire therapeutic range, 1-6 micrograms/ml. Total analysis time is 10-15 min.
- Published
- 1984
24. Amperometric detection of thiopurines in blood plasma with a cobalt-phthalocyanine chemically modified electrode after liquid chromatography
- Author
-
Richard P. Baldwin and Mary Kim Halbert
- Subjects
Detection limit ,Chromatography ,chemistry.chemical_element ,Biochemistry ,Fluorescence ,Amperometry ,Analytical Chemistry ,chemistry ,Electrode ,Blood plasma ,Environmental Chemistry ,Sample preparation ,Cobalt ,Spectroscopy ,Chemically modified electrode - Abstract
Cobalt phthalocyanine-containing carbon paste electrodes are used as electrocatalytic amperometric sensors for 6-mercaptopurine, 6-thioguanine, and several related thiopurines in blood plasma after separation by liquid chromatography. Required sample preparation is minimal, and total quantitation time is 8 min or less. Detection limits are 1.5–8 pmol, approximately an order of magnitude better than that obtained with ultraviolet or fluorescence detection.
- Published
- 1986
25. Electrocatalytic and analytical response of cobalt phthalocyanine containing carbon paste electrodes toward sulfhydryl compounds
- Author
-
Mary Kim Halbert and Richard P. Baldwin
- Subjects
Detection limit ,chemistry ,Electrode ,Analytical chemistry ,Cobalt phthalocyanine ,Chemical modification ,chemistry.chemical_element ,Carbon ,Amperometry ,Analytical Chemistry ,Nuclear chemistry - Abstract
Les electrodes du titre catalysent l'electrooxydation de composes tel que la cysteine, l'homocysteine, la N-acetylcysteine et le glutathion. Ces electrodes utilisees comme electrodes sensibles pour la detection amperometrique qui suit une chromatographie en phase liquide permettent la detection de ces composes
- Published
- 1985
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.