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 (kPL) 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 kPL 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.

MR‐Nucleomics: The study of pathological cellular processes with multinuclear magnetic resonance spectroscopy and imaging in vivo

“…9 This is also evidenced by the adoption of spiral-based Dixon methods, which essentially consist of the acquisition of an extremely concise spectrum. 158,159 For sodium imaging, because of the short biexponential T 2 relaxation, UTE was recommended to acquire the images in three dimensions with a nonselective hard excitation pulse. 160 3D multiecho radial imaging offers an efficient 23 Na multiparameter tissue compartment mapping that extends regular 23 Na imaging.…”

“…This is probably because clinical scenarios usually have determined targeting metabolites, making the nonspectroscopic readout techniques more time‐efficient for clinical scenarios 9 . This is also evidenced by the adoption of spiral‐based Dixon methods, which essentially consist of the acquisition of an extremely concise spectrum 158,159 …”

Metabolic imaging across scales reveals distinct prostate cancer phenotypes

“…Several clinical reports have shown the potential of HP- 13 C-MRI to detect PCa, assess disease aggressiveness, and detect tumour response to therapy [2][3][4][5][6][7] . Importantly, some of these studies have attempted to explain the mechanism of the observed tumour [1- 13 C]lactate labelling patterns by correlating imaging data with tissue-based metabolic biomarkers 2,[8][9][10] .…”

“…Several clinical reports have shown the potential of HP- 13 C-MRI to detect PCa, assess disease aggressiveness, and detect tumour response to therapy 2–7 . Importantly, some of these studies have attempted to explain the mechanism of the observed tumour [1- 13 C]lactate labelling patterns by correlating imaging data with tissue-based metabolic biomarkers 2,8–10 . However, a more comprehensive biological validation of HP- 13 C-MRI is required to assess its translational potential and navigate its use in specific clinical scenarios 11 .…”

Dynamic T2* relaxometry of hyperpolarized [1‐13C]pyruvate MRI in the human brain and kidneys

“…Hyperpolarized (HP) 13 C‐labeled MRI has shown its ability to investigate Smetabolic processes in vivo. In current clinical research, HP [1‐ 13 C]pyruvate MRI has been applied in human brain tumor studies, 1,2 prostate cancer studies, 3,4 cardiac studies, 5–7 breast cancer studies, 8 pancreatic cancer studies, 9 and renal cell carcinoma (RCC) studies 10,11 …”