Dual hyperpolarized [1-13C]pyruvate and [13C]urea magnetic resonance imaging of prostate cancer

Abstract

BackgroundAlthough multiparametric (mp) 1H magnetic resonance imaging (MRI) is increasingly used to detect and localize prostate cancer (PC), its correlation with tumor grade is limited. Hyperpolarized (HP) carbon-13 (13C) MR is an emerging imaging technique, which can be used to interrogate key biologic processes through in vivo detection of various HP probes. A distinct attribute of HP 13C MRI is the ability to detect multiple HP probes within a single acquisition. Here we report on the first simultaneous dual HP [1-13C]pyruvate and [13C]urea MRI with correlations to histopathologic findings in a patient with localized PC scheduled for radical prostatectomy. Material and methodsPaired HP 13C and standard mp 1H MRI were performed in a patient with biopsy-proven Gleason score 4 + 3 = 7 adenocarcinoma of the prostate scheduled for radical prostatectomy through a first-in-human pilot study of dual-agent HP MRI (NCT02526368). HP 13C MRI was performed using a clinical 3T scanner with 13C transmit-and-receive capabilities. Dynamic series of HP 13C pyruvate, lactate and urea imaging were acquired following intravenous (IV) injection of co-hyperpolarized [13C]urea (25 mM) and [1–13C]pyruvate (125 mM). The [1-13C]pyruvate-to-[1-13C]lactate conversion rate (kPL) was calculated using an inputless two-site exchange model; AUCurea was the [13C]urea signal summed over time. Following radical prostatectomy, whole-mount prostate histopathological slides were prepared and reviewed by an experienced genitourinary pathologist. ResultsFollowing informed consent, the patient underwent paired mp 1H MRI and dual-agent HP MRI. mp 1H MRI revealed a 1.2 cm lesion in the left apical posterior zone. Dual-agent HP MRI identified a focus of increased [1-13C]pyruvate-to-[1-13C]lactate conversion rate (kPL) extending from the left apical posterior peripheral zone to the right gland. A corresponding area of abnormal tissue perfusion (AUCurea) was seen in the left gland. Metabolism-perfusion mismatch (with several foci of increased kPL/AUCurea) was observed throughout the tumor. Tumor extension to the right midgland was confirmed at the time of radical prostatectomy and staining for lactate dehydrogenase-A was increased throughout the tumor relative to surrounding benign prostatic tissue. ConclusionThis first-in-human radiopathologic study demonstrates the feasibility of dual-agent HP MRI in PC patients. Simultaneous assessment of tumor metabolism and perfusion was able to detect occult disease as well as to show a significant mismatch between intra-tumoral metabolism and tissue perfusion in high-grade PC. Prospective validation of these findings is warranted.