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Bob C. Hamans¹, An Claes¹, Giulio Gambarota¹, Olaf van Tellingen², Pieter Wesseling¹, Cathy N. Maass¹, Arend Heerschap¹, William P.J. Leenders¹

¹Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ²Dutch Cancer Institute, Amsterdam, Netherlands

Use of USPIO as a blood pool contrast agent allows detection of (areas in) tumors that are invisible in conventional Gd-DTPA MRI because of an intact blood brain barrier, such as seen after anti-angiogenic therapy. USPIO imaging may provide more accurate tumor delineation in glioma therapy than conventional Gd-DTPA imaging.

Daniel Procissi¹, Thomas Sheung Chee Ng¹, ², Xiaowei Zhang¹, Yibao Wu³, Ciprian Catana⁴, Hargun Sohi¹, Simon R. Cherry³, Andrew A. Raubitschek⁵, Russell E. Jacobs¹

¹California Institute of Technology, Pasadena, California , USA; ²University of Southern California, Los Angeles, California , USA; ³University of California,  Davis, Davis, California , USA; ⁴Massachusetts General Hospital, Boston, Massachusetts, USA; ⁵City of Hope National Cancer Center, Duarte, California , USA

The ability to assess therapeutic response to cancer treatment is an essential requirement for the development of new types of therapeutic agents. In this perspective both PET and MRI provide unique windows into tumor microenvironment and can potentially probe therapy induced functional and anatomical changes of local tissue. Here we show how it is possible to design and implement an in vivo imaging protocol which allows the simultaneous acquisition of dynamic contrast enhanced (DCE), dynamic 18F-FDG PET and diffusion weighted imaging (DWI) with basic anatomical images using a combined PET/MR scanner.

Sanaz Arkani Jansen¹, Tatjana Paunesku, Gayle Woloschak, Stefan Vogt, Suzanne Conzen, Gillian M. Newstead, Gregory Karczmar

¹University of Chicago, Chicago, Illinois, USA

Greater sensitivity and specificity of DCEMRI to the preinvasive breast cancer ductal carcinoma in situ (DCIS) is needed. Furthermore, the mechanism for contrast enhancement of DCIS lesions on DCEMRI is not clear.  We show that: (i) murine DCIS lesions exhibit contrast uptake in vivo, and (ii) Gd-DTPA can leave blood vessels to enter mammary ducts distended with DCIS. This is a new insight into the mechanism for contrast enhancement of DCIS lesions in DCEMRI. Understanding the uptake of gadolinium in mammary ducts may lead to improvements in imaging methods, mathematical modeling and interpretation of DCEMRI data.

Balaji Krishnamachary¹, Marie-France Penet¹, Sridhar Nimmagadda¹, Meiyappan Solaiyappan¹, Dmitri Artemov¹, Kristine Glunde¹, Arvind P. Pathak¹, Venu Raman¹, Martin G. Pomper¹, Zaver M. Bhujwalla¹

¹The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

The discovery of cancer cells with stem-like markers offers new paradigms for understanding and treating tumor recurrence and metastasis.  These stem-like cancer cell populations are more drug resistant and more likely to metastasize.  Recent studies suggest that hypoxia provides a suitable niche for stem cells to maintain their precursor status.  We have previously shown in a human prostate cancer model that phosphocholine, total choline and choline kinase increase with hypoxia.  Here we show in a human breast cancer model that in addition to elevated total choline, the expression of CD44, a breast cancer stem cell marker, increases in hypoxic regions.

Denis Jean Rommel¹, Frank Peeters¹, Jorge Abarca-Quinones¹, Nicolas Christian¹, Max Lonneux¹, Anne Bol¹, Daniel Labar¹, Vincent Gregoire¹, Thierry Duprez¹

¹Universite Catholique de Louvain, 1200 Brussels, Belgium

We investigated in a rodent tumor model the correlation between choline concentration at 3.0 T H-MRS and the choline uptake at PET.  We recorded the early (72 hours) variations of the two parameters after external radiation therapy.  No significant pre-therapeutic correlation was found.  Opposite evolution after treatment was observed with expected decrease in choline concentration, but strong and paradoxical increase in choline uptake presumptively due to vasodilatation and reactive inflammatory changes.

Joel Richard Garbow¹, Sarah C. Jost¹, Xiang He¹, Dmitriy A. Yablonskiy¹

¹Washington University in St. Louis, Saint Louis, Missouri, USA

Tumor hypoxia and its downstream effects are of considerable interest in both basic and clinical oncology research due to their negative impact on response to various cancer therapies and promotion of metastasis. Diagnosing tumor hypoxia non-invasively could provide a significant advancement in cancer treatment and will be a key to implementing emerging targeted cancer therapies. Here we report the results of an initial study of hypoxia in a mouse model of high-grade glioma. Our approach to quantifying tumor hypoxia is based on a recently proposed Quantitative Blood Oxygenation Level Dependent (qBOLD) model of BOLD contrast in MRI.

Jadegoud Yaligar¹, Sunitha B. Thakur¹, Mihaela E. Lupu¹, Ya Wang¹, Cornelia C. Matei¹, Kristen L. Zakian¹, Jason A. Koutcher¹

¹Memorial Sloan-Kettering Cancer Center, New York, USA

Lactate is marker of tumor malignancy, hypoxia and  facilitates  progression of  malignant disease, there by defy tumor response to radiation and chemotherapy.  Aim of this study  to compare lactate concentration in  aggressive (R3327-AT) and indolent Dunning H (DH) prostate tumor to determine potential of lactate as  marker of tumor aggressiveness. Lactate is not detected at low tumor volume  and  is increased with  tumor volume 2200mm3 there after it decreased at 2500mm3 in R3327-AT tumors where as in DH tumors lactate is not detected at low tumor volume-high tumor volume. DCE-MRI parameters are decreased with increased tumor volume in both tumors.

Xiaomeng Zhang¹, Gary V. Martinez², Maria L. Garcia-Martin³, Mark Woods, Dean Sherry, Robert J. Gillies, ¹²

¹University of Arizona, Tucson, Arizona , USA; ²Arizona Cancer Center, Tucson, Arizona , USA; ³Instituto de Investigaciones Biomedicas, Spain

The extracellular pH (pHe) of cancers is acidic and inhibiting this acidity will inhibit metastases. Methods to image pHe in brain tumors based on relaxivity of a pH-dependent contrast reagent (CR), Gd-DOTA-4AmP were developed. We investigated the single injection of a mixture of DyDOTP with GdDOTA-4AmP. The ¦¤T1, and ¦¤T2* induced by the Gd-CR exhibited similar pH-dependence, while the pH-independent Dy-CR reduced T2* with negligible effects on the T1. Thus, with calibration, co-injection of this cocktail can enable dynamic calculation of spatially localized unique pH values.

Rui Vasco Simões¹, ², Sebastián Cerdán³, Carles Arús¹, ⁴

¹Universitat Autonoma de Barcelona, Cerdanyola del Vallès, Spain; ²Universidade de Coimbra, Coimbra, Portugal; ³Instituto de Investigaciones Biomedicas “Alberto Sols” UAM-CSIC, Madrid, Spain; ⁴Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain

Here we show that challenging tumor metabolism in vivo (mice bearing a GL261cells brain glioma) by a defined perturbation (hyperglycemia) produces MR spectral pattern changes when monitored by 1H-CSI, which recapitulate those recently described by single-voxel 1H-MRS. This gives us a first insight into brain tumor heterogeneity, as inspected from a dynamic response perspective to a certain metabolic challenge, and suggests a way for increasing the dynamic range of spectral pattern changes of use for improved brain tumor typing and grading.

Tracey Yik May Lui¹, ², Jonathan Ashchar Snir¹, ², Beth Dun¹, ², Alfred Harvey³, Ron Pettis³, Paula J. Foster¹, ²

¹Robarts Research Institute, London, Canada; ²University of Western Ontario, London, Canada; ³Becton Dickinson Techonologies, Durham, USA

The lymphatic system is a route in which cancer cells use to metastasize to distant parts of the body.  Once cancer cells are found in the lymph nodes a poor patient prognosis is to be expected.  Studying the behaviour of cancer cells in the lymphatic system is crucial to prevent/treat metastatic cancer.  Using cellular MRI techniques and a unique model involving the implantation of iron-labeled cancer cells directly into the lymph node of a mouse, we show for the first time that cancer cells which have disseminated from the primary tumor can be tracked in-vivo to a distant node.