Kayvan Keshari

Ferdia Gallagher

Shuyu Tang¹, Peder E.Z. Larson¹, Maxwell Meng¹, James Slater¹, Jeremy Gordon¹, Daniel B. Vigneron¹, and Zhen J. Wang^1
1University of California, San Francisco, San Francisco, CA, United States

We present our initial experience of applying HP ¹³C pyruvate MRI in patients with renal tumors. Distinct tumor metabolic pattern and heterogeneity can be observed on HP ¹³C pyruvate MRI.  Our data from subjects with two injections also suggests that the metabolite measurements are reproducible. This initial experience paves the way for this metabolic imaging technique to be applied for differentiating between benign renal tumors, low grade RCCs and high grade RCCs.

Nathaniel Kim¹, Arsen Mamakhanyan¹, Kristin Granlund¹, Elisa de Stanchina², Manish Shah³, Lewis Cantley^3,4, and Kayvan A. Keshari^1,3
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Weill Cornell Medical College, New York, NY, United States, ⁴Meyer Cancer Center, Weill Cornell Medical College, New York, NY, United States

We investigated hyperpolarized [1-¹³C] dehydroascorbic acid (HP DHA) as an imaging agent for probing oxidative stress in patient derived xenograft models (PDXs) of pancreatic cancer. By increasing the T₁ via D­₂O solvation and increasing the dose administered via awake mouse injection, conversion of DHA to ascorbate was readily observed in BRAF and KRAS mutant cancers. HP DHA was then used to characterize oxidative stress in these PDX models and their biochemical mechanism of response to ascorbate therapy. Changes in DHA/ascorbate metabolism were measured in these tumor models, demonstrating a proof of concept method for assessing ascorbate therapy in pancreatic cancer.

Thanh Phong Lê^1,2, Lara Buscemi³, Elise Vinckenbosch¹, Mario Lepore⁴, Lorenz Hirt³, Jean-Noël Hyacinthe^1,5, and Mor Mishkovsky^2
1Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland, ²Laboratory of Functional and Metabolic Imaging, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, ³Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Lausanne, Switzerland, ⁴Center for Biomedical Imaging - Animal Imaging and Technology (CIBM-AIT), École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁵Image Guided Intervention Laboratory, University of Geneva (UNIGE), Geneva, Switzerland

Stroke is a major cause of death and disability. Neuroprotective strategies could ameliorate patient recovery. Pyruvate and lactate were found neuroprotectant in preclinical studies of stroke models. Hyperpolarized ¹³C MRI provides a new way for real-time molecular imaging. In this work, we hyperpolarize those neuroprotective agents to study changes of their metabolism when administered at their therapeutic dose after ischemic stroke. We found that the metabolism of hyperpolarized lactate is significantly altered after transient cerebral ischemia, whereas moderate changes were depicted with hyperpolarized pyruvate. Those imply that hyperpolarized lactate would potentially be a better theranostic biosensor for stroke.

Casey Y Lee^1,2, Hany Soliman³, Benjamin J Geraghty^1,2, Nadia D Bragagnolo^1,2, Albert P Chen⁴, William J Perks⁵, Arjun Sahgal³, Michael W Chan⁶, Sean Symons⁷, and Charles H Cunningham^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ³Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴GE Healthcare Technologies, Toronto, ON, Canada, ⁵Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁶Diagostic Imaging, Trillium Health Partners, Mississauga, ON, Canada, ⁷Radiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Hyperpolarized ¹³C MRI was used to acquire images of [1-¹³C]lactate and ¹³C-bicarbonate from the injected [1-¹³C]pyruvate in 8 patients with brain metastases. Lesions were manually contoured and the mean tumor ¹³C-lactate signal was converted to a z-score by extending the approach previously described in Lee et al. (2019). As expected, the z-score ranks of the anatomical regions were less concordant in patients compared to controls. A range of lactate z-scores were observed in metastatic lesions, showing metabolic heterogeneity consistent with the known heterogeneity in metastatic features and clinical status. The lesions with the highest and 5^th highest lactate z-scores progressed.

Jun Chen¹, Evan LaGue², Junjie Li¹, Edward Hackett¹, Ian Corbin¹, Kelvin Billingsley², and Jae Mo Park^3,4
1AIRC, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ²Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA, United States, ³UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ⁴Electrical Engineering, University of Texas at Dallas, Richardson, TX, United States

Hyperpolarized [1-¹³C] glycerate was used to study the in vivo glycolytic activity in a rat model of hepatocellular carcinoma (HCC). Carbon-13 labeled glycolytic intermediate phosphorenolpyruvate (PEP) was detected in the tumor in addition to pyruvate and lactate peaks. The in vivo results were confirmed by high resolution ¹³C NMR spectra of tissue extracts, after steady-state infusion of [2,3-¹³C₂] glycerate. The results illustrate the potential of [1-¹³C] glycerate as a metabolic probe for assessing glycolytic flux.

James Timothy Grist¹, Christian Mariager², and Christoffer Laustsen^2
1University of Birmingham, Birmingham, United Kingdom, ²Aarhus University, Aarhus, Denmark

Hyperpoalrized ¹³C urea T₂ relaxometry has been previously used to assess the diabetic and ischemic kidney. In this study we utilise a novel fitting method (Laplacian) to visualise the extent of damage, through a reduction in bi-exponential relaxation behaviour, in a rodent model of renal ischemia.

 

This opens up a number of potential pre-clinical and clinical uses of hyperpoalrized ¹³C urea imaging providing a novel, and useful, readout of renal ischemia.