title: Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity.
abstract: Non-invasive imaging of lactate is of enormous significance in cancer and metabolic disorders where glycolysis dominates. Here, for the first time, we describe a chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method (LATEST), based on the exchange between lactate hydroxyl proton and bulk water protons to image lactate with high spatial resolution. We demonstrate the feasibility of imaging lactate with LATEST in lactate phantoms under physiological conditions, in a mouse model of lymphoma tumors, and in skeletal muscle of healthy human subjects pre- and post-exercise. The method is validated by measuring LATEST changes in lymphoma tumors pre- and post-infusion of pyruvate and correlating them with lactate determined from multiple quantum filtered proton magnetic resonance spectroscopy (SEL-MQC (1)H-MRS). Similarly, dynamic LATEST changes in exercising human skeletal muscle are correlated with lactate determined from SEL-MQC (1)H-MRS. The LATEST method does not involve injection of radioactive isotopes or labeled metabolites. It has over two orders of magnitude higher sensitivity compared to conventional (1)H-MRS. It is anticipated that this technique will have a wide range of applications including diagnosis and evaluation of therapeutic response of cancer, diabetes, cardiac, and musculoskeletal diseases. The advantages of LATEST over existing methods and its potential challenges are discussed.
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Catherine
authors.initials: C
authors.lastname: DeBrosse
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Ravi Prakash Reddy
authors.initials: RP
authors.lastname: Nanga
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Bagga
authors.affiliation: Laboratory of Molecular Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Kavindra
authors.initials: K
authors.lastname: Nath
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
authors.affiliation: Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Schnall
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008223:Lymphoma / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008819:Mice, Nude; D009132:Muscles / Q000033:anatomy & histology; D019047:Phantoms, Imaging; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase