Session ThOG. There are 5 abstracts in this session.

Session: HYPERPOLARIZATION IN IMAGING, time: 4:00 - 4:25 pm

Hyperpolarized 13C-Pyruvate DNP MRI Provides Novel Cellular Metabolic Data in Volunteers and Patients

Daniel B. Vigneron1, 3; Peder E. Z. Larson2; Jeremy Gordon1, 3; Yan Li2; Robert Bok1, 3; James Slater1, 3; Hsin-Yu Chen1, 3; Brian Chung1, 3; Jasmine Graham1, 3; Philip Lee1, 3; Yaewon Kim1, 3; Michael Ohliger1, 3; Jane Wang2; John Kurhanewicz4
1University of California, San Francisco, CA; 2University of California, Dept. of Radiology, San Francisco, CA; 3University of California, San Francisco, CA; 4University of California, San Francisco, San Francisco, CA

Just as MRI has shown value for medical imaging providing information beyond CT/X-ray, hyperpolarized 13C MRI can provide valuable stable isotope imaging biomarker information beyond what PET & SPECT can; and in a safe, fast, non-radioactive addition to current MRI exams. Experimental DNP HP C-13 MR enables direct investigations of cellular enzymatic kinetic rates in key metabolic pathways in humans. We developed specialized techniques for HP C-13 MRI with a focus on safety and benefit for investigating metabolism in healthy volunteers and in patients with prostate cancer, brain tumors, renal cancer, and metastatic cancers with [1-13C]pyruvate and recently [2-13C]pyruvate.

Session: HYPERPOLARIZATION IN IMAGING, time: 4:25 - 4:50 pm

Imaging the Metabolic Evolution of Glioblastoma throughout Tumor Progression to the Point of Relapse

Travis Salzillo1, 2; Joy Gumin1; Jaehyuk Lee1; Niki Zacharias1; Frederick Lang1, 2; Pratip Bhattacharya1, 2
1MD Anderson Cancer Center, Houston, TX; 2MD Anderson Cancer Center UTHealth Graduate School, Houston, TX

Glioblastoma is an aggressive brain cancer with a median survival of only 15 months despite standard-of-care treatment. Outcomes may be improved if the disease can be identified earlier in progression and if treatment can be rapidly assessed for efficacy. This project compared conventional T2-weighted magnetic resonance imaging (MRI) with a novel metabolic imaging modality called hyperpolarized MRI. By measuring the real-time conversion of injected hyperpolarized [1-13C] pyruvate to lactate with hyperpolarized MRI, tumor activity was detected sooner than with conventional MRI during 3 key stages of tumor progression: initial development, regression following radiotherapy treatment, and eventual relapse. These findings were supported by ex vivo metabolomics and histology data and suggest hyperpolarized MRI can provide significant value to the clinic.

Session: HYPERPOLARIZATION IN IMAGING, time: 4:50 - 5:05 pm

Deuterium metabolic imaging for in-vivo monitoring of pregnancy and pancreatic cancer in mice at 15.2 T.

Stefan Markovic1; Tangi Roussel2; Dina Preise1; Keren Sasson1; Avigdor Scherz1; Lucio Frydman1
1Weizmann Institute of Science, Rehovot, Israel; 2Center for Magnetic Resonance in Biology and Medic, Marseille, France

Recent breakthrough studies in brain and in tumors suggest that deuterium MRS(I) could have highly desirable properties for imaging glycolysis and its metabolic products.1,2 This study followed the uptake and metabolism of D6,6’-glucose in pregnant mice and in mice implanted with a pancreatic cancer tumor model, using 2H MRSI at 15.2 T. Over a period ≥2 h, glucose uptake was observed in the placenta and in certain fetal organs like the liver for the pregnant animals, as well as in the pancreatic tumors. Main metabolic products include lactate and HDO, which were produced in individual organs with distinct time traces. This suggests that 2H-based metabolic MRSI may offer new ways of monitoring health and disease in these challenging abdominal cases.

Session: HYPERPOLARIZATION IN IMAGING, time: 5:05 - 5:20 pm

Hyperpolarized 13C-Pyruvate MRI and PSMA-PET of Prostate Cancer in the Clinical Setting of Primary Staging – A Case Study

Hsin-Yu Chen; Robert A. Bok; Jeremy W. Gordon; Mark van Criekinge; Lucas Carvajal; James B. Slater; Thomas A. Hope; Peder E.Z. Larson; Rahul Aggarwal; Peter R. Carroll; John Kurhanewicz; Daniel B. Vigneron
University of California, San Francisco, CA

Hyperpolarized 13C (HP 13C) MRI is an emerging molecular imaging technology based on dissolution DNP that provides >50,000x signal enhancement. This case study investigated the role of HP 13C-pyruvate MRI and PSMA-PET in the primary staging setting on a high-risk prostate cancer patient. HP 13C-pyruvate is a 5-minute addition to the standard of care prostate mpMRI, and the rate of pyruvate-to-lactate conversion(kPL) spatially mapped aggressive cancer and predicted adverse pathologic features found at surgical pathology. PSMA-PET confirmed the presence of primary tumor and identified locoregional lymph node involvement. Overall, the combined use of HP 13C MRI and PSMA-PET provided key staging information, and has great potential to improve future management of prostate cancer.

Session: HYPERPOLARIZATION IN IMAGING, time: 5:20 - 5:35 pm

Novel Real-time Hyperpolarized 13C Metabolic Tracer Probes gamma-Glutamyl Transferase Activities in vivo Human Tumor Xenografts

Kazutoshi Yamamoto1; Tomohiro Seki1; Nobu Oshima1; Marino Itoda2; Yohei Kondo2; Yutaro Saito2; Yoichi Takakusagi2; Shun Kishimoto1; Jeffrey Brender1; Ronja Malinowski3; Jan Henrik Ardenkjær-Larsen3; Hiroshi Nonaka2; Murali Krishna1; Shinsuke Sando2
1National Institutes of Health, NCI, Bethesda, MD; 2University of Tokyo, Bunkyo-ku, Japan; 3Technical University of Denmark, Lyngby, Denmark

Although the dissolution dynamic nuclear polarization approach overcome the relatively poor MR sensitivity of in vivo metabolites, the limited number of available hyperpolarized 13C probes reminds a drawback.  Here, we synthesized novel gamma-glutamyl transferase (GGT) probe as a promising hyperpolarizing probe.  It is well known that dysregulation of GGT activities in malignant cells leads to more aggressive phenotypes by producing reactive oxygen species.  GGT is important for glutathione homeostasis and has been used as a diagnostic marker for various pathologies.   In this presentation, for the first time, a novel hyperpolarized GGT probe was demonstrated in in vivo human tumor xenografts to detect real-time GGT as a prospective biomarker for monitoring the tumor progression and prognosis with/without cancer therapeutic approaches.