Dataset Information

Hyperpolarized ¹³C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

ABSTRACT: Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-¹³C]pyruvate (HP-¹³C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-¹³C-MRI and conventional proton (¹H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (k_PL) between ¹³C-pyruvate and ¹³C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing k_PL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional ¹H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-¹³C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-¹³C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

SUBMITTER: Ursprung S

PROVIDER: S-EPMC8773685 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Ursprung Stephan S Woitek Ramona R McLean Mary A MA Priest Andrew N AN Crispin-Ortuzar Mireia M Brodie Cara R CR Gill Andrew B AB Gehrung Marcel M Beer Lucian L Riddick Antony C P ACP Field-Rayner Johanna J Grist James T JT Deen Surrin S SS Riemer Frank F Kaggie Joshua D JD Zaccagna Fulvio F Duarte Joao A G JAG Locke Matthew J MJ Frary Amy A Aho Tevita F TF Armitage James N JN Casey Ruth R Mendichovszky Iosif A IA Welsh Sarah J SJ Barrett Tristan T Graves Martin J MJ Eisen Tim T Mitchell Thomas J TJ Warren Anne Y AY Brindle Kevin M KM Sala Evis E Stewart Grant D GD Gallagher Ferdia A FA

Cancers 20220111 2

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operat ...[more]

PMID: 35053497

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Project description:The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.

Dataset Information

Hyperpolarized ¹³C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Publications

Hyperpolarized <sup>13</sup>C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

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Dataset Information

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Publications

Hyperpolarized &lt;sup&gt;13&lt;/sup&gt;C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Hyperpolarized ¹³C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Hyperpolarized <sup>13</sup>C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.