Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET): feasibility of a new imaging concept using a clinical PET/MRI scanner

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-CO 2 ( 13 C-HCO 3 ) 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.