Nathaniel Kim¹, Marjan Berishaj¹, Elisa de Stanchina², Manish Shah³, Lewis Cantley⁴, and Kayvan Keshari^1
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, United States, ⁴Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY, United States

HP DHA was demonstrated as an imaging agent for probing the biochemical response to ascorbate therapy in patient derived xenograft (PDX) models of cancer. Changes in DHA/ascorbate metabolism were observed in PDX tumors after prolonged treatment, mirroring the observed treatment response to high dose ascorbate. Metabolomic studies showed that high dose ascorbate therapy induced oxidative stress, leading to increased flux through the pentose phosphate pathway (PPP). DNA damage repair mutants exhibit lower baseline flux through the PPP and are more sensitized to ascorbate induced ROS. These results demonstrate a new method for assessing oxidative stress in vivo using HP DHA.

Dita Pajuelo¹, Alberto Malucelli², Monika Dezortová¹, Antonín Škoch¹, Robert Bartoš², Martin Sameš², and Milan Hájek^1
1MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²Department of Neurosurgery, JE Purkyne University and Masaryk Hospital, Ústí nad Labem, Czech Republic

Differential diagnosis between brain tumor recurrence and radionecrosis is still problematic. MR Spectroscopy Imaging (MRSI) is useful in differentiating between these two histologically and radiologically distinct entities. Six methods with different combination of metabolic parameters were used to compare 37 lesions examined by 2D/3D MRSI. The lesional and contralateral comparison of choline-containing compounds and lactate using long echo time achieved the highest sensitivity and specificity. Choline to creatine ratio showed low specificity. The distinction of regressive recurrence as a separate entity is helpful in the effort to discern the complexity of events leading to new enhancing lesions in neurooncologic patients.

Rossella Canese¹, Miriam Dolciami², Claudia Testa³, and Lucia Manganaro^2
1Core Facilities, Istituto Superiore di Sanita', Rome, Italy, ²Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I Sapienza University of Rome, Rome, Italy, ³Department of Physics and Astronomy, University of Bologna, Bologna, Italy, Rome, Italy

Cervical cancer (CC) is the fourth most common malignancy and cancer-related mortality cause in women worldwide. A significant portion of these patients are diagnosed as locally advanced cervical cancer (LACC), thus requiring combined therapies. We investigate the role of the lipid signal derived from 1H magnetic resonance (MR)-spectroscopy in assessing response to neoadjuvant chemotherapy of LACC.

Daniel Robert Crooks¹, Ye Yang², Andrew Lane³, Teresa Fan³, Jeffrey Brender⁴, Murali C Krishna⁴, and W. Marston Linehan^1
1Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, United States, ²National Cancer Institute, Bethesda, MD, United States, ³Center for Environmental Systems Biochemistry, University of Kentucky, Lexington, KY, United States, ⁴Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States

NMR-based analyses of lipids can shed insight into the global complement of cellular lipids, and elucidate the fuel sources and pathways contributing to lipid biosynthesis in cells grown in the presence of 13C-labeled fuels. We utilized 1H-13C HSQC NMR analysis of cellular lipids derived from FH- and mtDNA deficient UOK271 cells and observed robust reductive carboxylation of glutamine that resulted in formation and incorporation of 13C-glutamine-derived acetyl groups into lipid chains.

Abdelazim Elsayed Elhelaly^1,2, Fuminori Hyodo¹, Norikazu Koyasu³, Hiroyuki Tomita⁴, Masaharu Murata⁵, Yoshifumi Noda³, Hiroki Kato³, and Masayuki Matsuo^3
1Department of Radiology, Frontier Science for Imaging, Gifu University, Gifu, Japan, ²Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt, ³Department of Radiology, Gifu University, Gifu, Japan, ⁴Department of Tumor Pathology, Gifu University, Gifu, Japan, ⁵Innovation Center for Medical Redox Navigation, Kyushu University, Kyushu, Japan

DNP highly improves the sensitivity of magnetic resonance spectroscopy allowing for greater insight into in vivo metabolic activity. We used our dissolution ¹³C DNP system to monitor the Warburg effect in MIA PaCa human pancreatic carcinoma model mice subjected to radiotherapy or chemotherapy. In vivo production of ¹³C lactate in tumors showed a significant reduction after radiation therapy. Mice subjected to anticancer drugs also showed a significant reduction in the relative production of ¹³C lactate at an early stage of the treatment course before any anatomical changes in the structure or size of the tumors were detectable by MRI images.

Dante Capaldi¹, Jen-Yeu Wang², Vipul Sheth², Elizabeth Kidd², and Dimitre Hristov^2
1University of California, San Francisco, San Francisco, CA, United States, ²Stanford University, Stanford, CA, United States

IVIM MRI provides measurements of diffusion and perfusion, which has been shown to be predictive of prognosis, responsive to chemoradiotherapy, and correlated with DCE MRI in cervical cancer.  We hypothesized that IVIM in cervical cancer patients would be sensitive to CCRT, and hence our objective was to first investigate changes in IVIM in cervical cancer patients undergoing adjuvant CCRT and evaluate the relationship between these metrics with changes in tumor volume and PET.  Preliminary results show that IVIM measurements are related to both PET and changes in overall tumor volume and may reflect changes in the tumor microenvironment during treatment.

Paola Scifo¹, Paola Mapelli^1,2, Samuele Ghezzo², Ana Maria Samanes Gajate¹, Erik Preza¹, Giorgio Brembilla^2,3, Vito Cucchiara^2,4, Naghia Ahmed⁵, Carolina Bezzi^1,2, Annarita Savi¹, Ilaria Neri¹, Ettore Di Gaeta³, Luigi Gianolli¹, Massimo Freschi⁵, Alberto Briganti^2,4, Francesco De Cobelli^2,3, and Maria Picchio^1,2
1Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy, ²Vita-Salute San Raffaele University, Milan, Italy, ³Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy, ⁴Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy, ⁵Department of Pathology IRCCS San Raffaele Scientific Institute, Milan, Italy

The use of PET/MRI scanners is an innovative approach to stage prostate cancer (PCa) and the combined use of both 68Ga-PSMA and 68Ga-DOTA-RM2 radiotracers can improve disease staging by providing different metabolic aspects of the tumour. In the present study, 13 patients with high-risk PCa undergoing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI before radical prostatectomy have been included, with availability of histology as gold standard to validate intraprostatic findings and local extension. Our results suggest that the use of PET/MRI with a dual tracer approach can improve PCa staging, by providing complementary information ameliorating disease characterization.

Friederike Hesse¹, Alan Wright¹, Vencel Somai^1,2, Flaviu Bulat^1,3, and Kevin Brindle^1,4
1CRUK CI, University of Cambridge, Cambridge, United Kingdom, ²Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ³Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, ⁴Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

Metabolic imaging of brain tumor responses to radio-chemotherapy can give an early indication of treatment outcome. We show here that Deuterium Metabolic Imaging (DMI) with ²H-labeled fumarate is more sensitive than diffusion weighted ¹H imaging (DWI) in detecting early evidence of cell death following radio-chemotherapy in orthotopically implanted patient-derived glioblastoma xenografts. ²H spectra were acquired from tumors with a time resolution of 5min, following an injection of ²H-labelled fumarate. Within 48h after the last chemo-radiotherapy treatment (CRT) the rate of tumor malate production from labelled fumarate increased significantly, whereas changes in ADC values were only detectable 7 days post treatment. 

Victoria Laney¹, Ryan Hall ¹, Grace Yeung¹, Victoria Laney¹, Suneel Apte ², and Zheng-Rong Lu^3
1Case Western Reserve University, CLEVELAND, OH, United States, ²Cleveland Clinic Foundation, CLEVELAND, OH, United States, ³Case Western Reserve University, Cleveland, OH, United States

PDAC is a highly aggressive malignant cancer and the 3rd leading cause of cancer related deaths in the US. Currently, treatment options for patients are limited due to late detection of the tumors and lack of effective therapies. The aggressive nature of PDAC is in part due to the desmoplastic tumor microenvironment. MiR-200c regulates epithelial-to-mesenchymal transition and extracellular remodeling for effective treatment of aggressive tumors. In this study, we investigate the effectiveness of MR molecular imaging of extradomain-B fibronectin, an extracellular matrix oncoprotein associated with EMT, for non-invasive monitoring of PDAC tumor response to miR-200c therapy in a mouse model.

Gulnur Semahat Ungan^1,2, Albert Pons Escoda³, Daniel Ulinic², Carles Arús^1,2, Alfredo Vellido⁴, Carles Majós^1,3, and Margarida Julià-Sapé^1,2
1Centro de Investigación Biomédica en Red, Barcelona, Spain, ²Universitat Autònoma de Barcelona, Barcelona, Spain, ³Institut d'Investigació Biomèdica de Bellvitge (Idibell), Hospital Universitari de Bellvitge, Barcelona, Spain, ⁴IDEAI-UPC research center, UPC BarcelonaTech, Barcelona, Spain

A blind source separation method (cNMF) was used to extract characteristic metabolic patterns from PRESS MRSI 3T acquired from areas of contrast enhancement in a retrospective set of 31 glioblastoma patients, one month after the end of concomitant chemoradiotherapy with temozolomide. The aim was to evaluate whether these patterns were predictive of true progression or pseudoprogression. They were used as input for supervised classifiers, achieving a maximum of 81% balanced accuracy. A moderate association between extracted patterns and outcome was detected by Cramer’s V. Spatial source distribution with nosologic maps points to MRSI-detected metabolic heterogeneity as cause for classifiers’ performance.