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1.
Proc Natl Acad Sci U S A ; 120(49): e2312261120, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38011568

ABSTRACT

While radical prostatectomy remains the mainstay of prostate cancer (PCa) treatment, 20 to 40% of patients develop postsurgical biochemical recurrence (BCR). A particularly challenging clinical cohort includes patients with intermediate-risk disease whose risk stratification would benefit from advanced approaches that complement standard-of-care diagnostic tools. Here, we show that imaging tumor lactate using hyperpolarized 13C MRI and spatial metabolomics identifies BCR-positive patients in two prospective intermediate-risk surgical cohorts. Supported by spatially resolved tissue analysis of established glycolytic biomarkers, this study provides the rationale for multicenter trials of tumor metabolic imaging as an auxiliary tool to support PCa treatment decision-making.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Prostate-Specific Antigen/analysis , Lactic Acid , Prospective Studies , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostate/pathology , Prostatectomy/methods , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Retrospective Studies
2.
Neuroimage ; 257: 119284, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35533826

ABSTRACT

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.


Subject(s)
Bicarbonates , Magnetic Resonance Imaging , Bicarbonates/metabolism , Brain/diagnostic imaging , Brain/metabolism , Carbon Isotopes/metabolism , Deuterium/metabolism , Glucose/metabolism , Humans , Lactic Acid/metabolism , Magnetic Resonance Imaging/methods , Pyruvic Acid
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