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Hyperpolarised ¹³C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

ABSTRACT: Hyperpolarised magnetic resonance imaging (HP ¹³C-MRI) is an emerging clinical technique to detect [1-¹³C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-¹³C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-¹³C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP ¹³C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-¹³C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP ¹³C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

SUBMITTER: Sushentsev N

PROVIDER: S-EPMC8786834 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Sushentsev Nikita N McLean Mary A MA Warren Anne Y AY Benjamin Arnold J V AJV Brodie Cara C Frary Amy A Gill Andrew B AB Jones Julia J Kaggie Joshua D JD Lamb Benjamin W BW Locke Matthew J MJ Miller Jodi L JL Mills Ian G IG Priest Andrew N AN Robb Fraser J L FJL Shah Nimish N Schulte Rolf F RF Graves Martin J MJ Gnanapragasam Vincent J VJ Brindle Kevin M KM Barrett Tristan T Gallagher Ferdia A FA

Nature communications 20220124 1

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry ...[more]

PMID: 35075123

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Project description:Hyperpolarised [1-13C]pyruvate MRI (HP-13C-MRI) is an emerging metabolic imaging technique that has shown promise for evaluating prostate cancer (PCa) aggressiveness. Accurate tumour delineation on HP-13C-MRI is vital for quantitative assessment of the underlying tissue metabolism. However, there is no consensus on the optimum method for segmenting HP-13C-MRI, and whole-mount pathology (WMP) as the histopathological gold-standard is only available for surgical patients. Although proton MRI can be used for tumour delineation, this approach significantly underestimates tumour volume, and metabolic tumour segmentation based on HP-13C-MRI could provide an important functional metric of tumour volume. In this study, we quantified metabolism using HP-13C-MRI and segmentation approaches based on WMP maps, 1H-MRI-derived T2-weighted imaging (T2WI), and HP-13C-MRI-derived total carbon signal-to-noise ratio maps (TC-SNR) with an SNR threshold of 5.0. 13C-labelled pyruvate SNR, lactate SNR, TC-SNR, and the pyruvate-to-lactate exchange rate constant (kPL) were significantly higher when measured using the TC-SNR-guided approach, which also corresponded to a significantly higher tumour epithelial expression on RNAscope imaging of the enzyme catalysing pyruvate-to-lactate metabolism (lactate dehydrogenase (LDH)). However, linear regression and Bland-Altman analyses demonstrated a strong linear relationship between all three segmentation approaches, which correlated significantly with RNA-scope-derived epithelial LDH expression. These results suggest that standard-of-care T2WI and TC-SNR maps could be used as clinical reference tools for segmenting localised PCa on HP-13C-MRI in the absence of the WMP gold standard. The TC-SNR-guided approach could be used clinically to target biopsies towards highly glycolytic tumour areas and therefore to sample aggressive disease with higher precision. KEY POINTS: • T2WI- and TC-SNR-guided segmentations can be used in all PCa patients and do not explicitly require WMP maps. • Agreement between the three segmentation approaches is biologically validated by their strong relationship with epithelial LDH mRNA expression. • The TC-SNR-guided approach can potentially be used to identify occult disease on 1H-MRI and target the most glycolytically active regions.

Project description:PurposeTo assess 68Ga-PSMA PET/CT for detection of low- and intermediate-risk prostate cancer (PCa), high-risk PCa in comparison with mpMRI, respectively, and to determine which of low- and intermediate-risk PCa are more likely to be detected by 68Ga-PSMA PET/CT.MethodsWe conducted a retrospective analysis of patients who had undergone a prostate biopsy and/or radical prostatectomy and who were scanned with 68Ga-PSMA PET/CT and mpMRI between June 2019 and March 2021. The mpMRI images were scored with the Prostate Imaging-Reporting and Data System Version 2.1 (PI-RADS) and were classified as either negative (PI-RADS 1-3) or positive (PI-RADS 4-5). Suspicious 68Ga-PSMA PET/CT lesions were reviewed for each relevant patient and classified by double-trained board-certified nuclear medicine physicians. The results were evaluated with the histopathological outcome. All patients were classified according to the D'Amico classification, and the clinical data were combined for stratified analysis.ResultA total of 101 patients who were pathologically diagnosed with PCa were analyzed. Of the 101 patients, 88 (80.6%) patients presented with a pathologic mpMRI, and 85 (79.1%) with a pathologic 68Ga-PSMA PET/CT. In the high-risk PCa cohort, 68Ga-PSMA PET/CT was positive in 64/66 (97.0%) patients and yielded a higher detection rate than that for the mpMRI patients (58/66, 87.9%; p < 0.05). However, mpMRI provided superior diagnostic confidence in identifying low- and intermediate-risk PCa (30/35, 85.7% vs. 21/35, 60.0%; p < 0.05). When the age threshold exceeded 62.5 years and the serum prostate specific antigen (PSA) threshold exceeded 9.4 ng/ml, a higher uptake of PSMA was more likely to occur in the lesions of low- and intermediate-risk PCa.ConclusionThe diagnostic performance of 68Ga-PSMA PET/CT was superior to that of mpMRI in the high-risk PCa cohort, which was consistent with prior studies. Furthermore, in the initial diagnosis of low- and intermediate-risk PCa, we found that mpMRI showed a higher diagnostic accuracy than 68Ga-PSMA PET/CT did. Low- and intermediate-risk PCa patients with a PSA ≥ 9.4 ng/ml and age ≥ 62.5 years were more likely to have a positive 68Ga-PSMA PET/CT result.

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Hyperpolarised ¹³C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

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Hyperpolarised <sup>13</sup>C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

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Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

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Hyperpolarised &lt;sup&gt;13&lt;/sup&gt;C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

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OmicsDI is part of the ELIXIR infrastructure

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Hyperpolarised ¹³C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised <sup>13</sup>C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.