title: Simultaneous hyperpolarized (13)C-pyruvate MRI and (18)F-FDG-PET in cancer (hyperPET): feasibility of a new imaging concept using a clinical PET/MRI scanner.
abstract: In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO2 ((13)C-HCO3) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark ; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gutte
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Hansen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark ; Department of Electrical Engineering, Technical University of Denmark Lyngby, Denmark.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Henriksen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Helle H
authors.initials: HH
authors.lastname: Johannesen
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark Lyngby, Denmark ; GE Healthcare Brøndby, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Ardenkjaer-Larsen
authors.affiliation: CEA Saclay, I2BM, NeuroSpin, UNIRS Gif sur Yvette, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vignaud
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen Denmark ; Center for Nanomedicine and Theranostics, Technical University of Denmark Denmark.
authors.forename: Anders E
authors.initials: AE
authors.lastname: Hansen
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg C, Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Børresen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Klausen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Anne-Mette N
authors.initials: AM
authors.lastname: Wittekind
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Nic
authors.initials: N
authors.lastname: Gillings
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg C, Denmark.
authors.forename: Annemarie T
authors.initials: AT
authors.lastname: Kristensen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark ; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Clemmensen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen Denmark ; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
keywords: 13C-pyruvate; 18F-FDG-PET; Cancer; DNP; MR; PET/MR; hyperpolarized; molecular imaging; response monitoring