Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity

Catherine DeBrosse, Ravi Prakash Reddy Nanga, Puneet Bagga, Kavindra Nath, Mohammad Haris, Francesco Marincola, Mitchell D. Schnall, Hari Hariharan, Ravinder Reddy

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number19517
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 22 Jan 2016

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Lactic Acid
Biomarkers
Protons
Lymphoma
Neoplasms
Skeletal Muscle
Exercise
Musculoskeletal Diseases
Glycolysis
Pyruvic Acid
Radioisotopes
Hydroxyl Radical
Heart Diseases
Healthy Volunteers
Magnetic Resonance Imaging
Injections
Water

ASJC Scopus subject areas

  • General

Cite this

Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity. / DeBrosse, Catherine; Nanga, Ravi Prakash Reddy; Bagga, Puneet; Nath, Kavindra; Haris, Mohammad; Marincola, Francesco; Schnall, Mitchell D.; Hariharan, Hari; Reddy, Ravinder.

In: Scientific Reports, Vol. 6, 19517, 22.01.2016.

Research output: Contribution to journalArticle

DeBrosse, C, Nanga, RPR, Bagga, P, Nath, K, Haris, M, Marincola, F, Schnall, MD, Hariharan, H & Reddy, R 2016, 'Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity', Scientific Reports, vol. 6, 19517. https://doi.org/10.1038/srep19517
DeBrosse, Catherine ; Nanga, Ravi Prakash Reddy ; Bagga, Puneet ; Nath, Kavindra ; Haris, Mohammad ; Marincola, Francesco ; Schnall, Mitchell D. ; Hariharan, Hari ; Reddy, Ravinder. / Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity. In: Scientific Reports. 2016 ; Vol. 6.
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