2009 MIPS Molecular Imaging Seminar Series

Seminar 4:30 − 5:15 pm
Discussion 5:15 − 5:30 pm

January 26, 2009

Cellular Responses to Nucleotide Depletion

Beverly Mitchell, George E. Becker Professor in Medicine and Professor, by courtesy, of Chemical and Systems Biology, Dept. of Medicine Oncology

February 2, 2009
Clark Auditorium

Jeff Bulte, PhD 
Prof. Radiology, Biomed Eng And Chem & Biomol Eng
Dir, Cellular Imaging Section, Institute for Cell Engineering
Johns Hopkins

MR-Guided Cell Delivery and Cell Tracking: From Imaging to Intervention 


The clinical development of novel immune and stem cell therapies calls for suitable methods that can follow the fate of cells non-invasively in humans at high resolution. Our lab has developed several methods to label cells magnetically (using tiny superparamagnetic iron oxide nanoparticles) in order to make them visible by MR imaging. Following years of extensive animal research, in 2005 this technology was introduced in the clinic uaing dendritic cell cancer vaccines. MRI cell tracking is further pursued in animal models of de- and dys-myelination, multiple sclerosis, brain tumors, spinal cord injury, stroke, and cardiovascular disease. 

Novel reporter genes are also being developed that can provide contrast on MRI scans. Artificial proteins are being designed, cloned, and expressed in mammalian cells that contain specific proton exchangable groups of which the proton signal can be manipulated. Instead of directly labeling cells, we have also shown that semi-permeable alginate microcapsules can be loaded with multimodal contrast agents while offering simultaneous immunoprotection of cellular therapeutics. While the Bulte lab is primarily doing basic and pre-clinical research, there is a strong interaction with the clinical interventional radiology and oncology groups in order to bring the methodologies into the clinic.

February 23, 2009

Affibody Based PET Probes for Cancer Molecular Imaging

Zhen Cheng, PhD
Asstistant Professor of Radiology, Stanford

March 9, 2009
Clark Auditorium

Juri Gelovani, MD, PhD
Univ of Texas MD Anderson Cancer Center

Imaging HIF-1 and its significance in tumor biology


The current presentation will discuss the mechanism and spatio-temporal dynamics of HIF-1 mediated responses to radiation in well characterized tumor reporter cell lines stably transfected with a bifunctional genetic reporter consisting of herpes simplex virus 1-thymidine kinase (HSV-tk) and green fluorescent protein (GFP) under transcriptional control of multiple tandem repeats of the hypoxia response element (Serganova et al., 2004; Wen et al., 2004). Repetitive, non-invasive whole body molecular-genetic PET imaging of HIF-1 signaling in mice is achieved through selective retention in tumors of 18F-labeled reporter substrate 2-fluoro-2-deoxy-1-D-arabionofuranosyl-5-ethyl-uracil (FEAU). Our hypothesis was that selective HIF-1 therapy potentially provides a wider spectrum of radiosensitizing effects than inhibition of individual downstream effectors, with fewer available mechanisms for resistance. In sharp contrast to mechanisms suggested by the prior report by Moeller, et al, (2004), our results indicate that tumor cell HIF-1 signaling is closely associated with microenvironmental ischemia. Specifically, we demonstrate in monolayer cultures and multicellular spheroids that radiation inhibits HIF-1 transcriptional activity in a dose dependent manner up to 16 Gy. In sharp contrast, in vivo irradiation of HIF-reporter tumor xenografts with 8 Gy yields delayed hypoxia-dependent upregulation of HIF-1 signaling at 48 hours. Functional MRI, power Doppler ultrasound, and immunohistochemical in situ analysis demonstrate that the delayed upregulation of HIF-1 signaling and VEGF production in the tumor cell compartment is induced by radiation-specific disruption of stromal endothelium and vascular integrity, and by the subsequent loss of perfusion and increased ischemia. This secondary ischemia-induced upregulation of HIF-1 signaling in tumor cells serves as the adaptive mechanism for stromal revascularization responsible for tumor resistance to radiotherapy. Further proof of this mechanism was provided by inhibition of HIF-1 signaling using the selective inhibitor PX-478 (Welsh et al., 2004), which suppressed adaptive tumor revascularization and sensitized tumors to radiation. Taken together, these data clearly demonstrate that tumor radioresistance is mediated by tumor-stromal interactions and by the capacity of tumor to compensate for radiation-induced vascular collapse and ischemia through secondary upregulation of HIF-1 dependent pro-angiogenic signaling. Selective inhibition of HIF-1 mediated VEGF signaling is a promising strategy for restoring tumor radiosensitivity.

March 16, 2009

Intravascular Ultrasound

Paul Yock, MD
Martha Meier Weiland Professor, Bioengineering and Medicine
Director, Program in Biodesign, Stanford University

April 6, 2009
Clark Auditorium

Robert H. Mach, PhD
Prof. Radiology
Washington Univ. School of Medicine

The Sigma-2 Receptor: a Biomarker for Imaging the Proliferative Status of Solid Tumors


The development of radiotracers for imaging cell proliferation in solid tumors has focused on radiolabeled thymidine analogs which measure the salvage pathway of DNA synthesis. However, since thymidine analogs provide a measure the S phase fraction of a tumor, they are unable to discriminate between proliferating cells in G1 and G2/M phases of the cell cycle and cancer cells driven into quiescence (G0) by nutrient deprivation and hypoxia. This talk will focus on the characterization of the sigma-2 receptor as a Ki-67-like biomarker for imaging cell proliferation, and the development of radiotracers for imaging the sigma-2 receptor status of solid tumors in vivo with Positron Emission Tomography (PET).

Apr 27, 2009

Planar cell polarity: from cells to tissues to organisms

Jeff Axelrod
Associate Professor, Department of Pathology, Stanford.

May 4, 2009

18F-labeled RGD peptides: an update
Scott Liu, Chen lab

May 11, 2009
Clark Auditorium

Alexander L. (Sasha) Kalibanov, PhD
Prof, Div of CV Med & Dept of Biomed Eng
University of Virginia

Targeted Microbubbles - Ultrasound Contrast Agents for Molecular Imaging and Drug Delivery


Ultrasound traditionally (8-15 years ago) was regarded as an imaging modality unfit for targeted/molecular imaging. However, microbubble contrast agents can be decorated with targeting ligands, and ligand-targeted bubbles do attach to the receptor-coated surfaces quite effectively. Clinical ultrasound imaging systems allow detection of individual microbubbles (with micrometer size and picogram mass). Therefore, molecular imaging with ultrasound contrast agents is feasible.

June 1, 2009
Clark Auditorium

Duane A. Mitchell, MD, PhD
Asst. Prof., Neurology 
Assoc. Dir., Duke Brain Tumor Immunotherapy Program

Adoptive Cellular Therapy for Treatment of Malignant Glioma: Opportunities for Bioimaging

June 8, 2009
Clark Auditorium

Bertrand Tavitian, MD
Prof. Biochem
Head, Laboratoire d'Imagerie moléculaire expérimentale (Experimental Molecular imaging Lab) at the CEA-Inserm in Orsay, France

Molecular imaging with oligonucleotides 


Molecular Imaging can assess gene expression non–invasively, repeatedly and quantitatively in living subjects. Pharmaco-Imaging of oligonucleotides allows quantifying in 3-D and in the whole bodies of animals and Humans the bio-distribution time course of antisense, aptamers, interfering RNAs, ribozymes, etc. The methodology and examples of applications for the assessment of targeting and delivery of oligonucleotides will be presented.

Use of oligonucleotides as diagnostic contrast agents is a longer way ahead of us and remains still an open question. It will require that a sufficient contrast is obtained in vivo and a correlation between tracer and target concentrations, two issues that are yet to be demonstrated.

June 15, 2009
Clark Auditorium

Kurt Zinn, DVM, PhD
Prof. Rad, University of Alabama at Birmingham (UAB)

Cancer Therapy Targeting Death Receptor 5 



June 29, 2009

Targeted Molecular Imaging, a Random and a Rational Approach

Julie Sutcliffe, Ph.D,
Associate Professor, Dept. of Biomedical Engineering, UC Davis, CA

July 6, 2009

A Cell-compatible Condensation Reaction for Controlled In Vivo Synthesis of Nanostructures
Marybeth Pysz, Willmann lab

Clinically-Translatable Microbubbles for Cancer Detection and Monitoring with Molecular Ultrasound
Gaolin Liang, Rao Lab

Steven Conolly, PhD
UC Berkeley Bioengineering
Chair, UCSF/UC Berkeley Graduate Group in BioE
Vice Chair of Undergraduate Affairs

Instrumentation for MRI and Magnetic Nano-Particle Imaging


My research group at Berkeley focuses on instrumentation advances for medical imaging, with a special emphasis in magnetic imaging methods. Here I will overview two recent research projects, conducted in collaboration with Stanford researchers.

Magnetic Nano-Particle Imaging is a brand new imaging modality that offers 300 micron resolution, no attenuation with depth, and has great promise for 100-fold increase in Contrast to Noise Ratio (CNR) relative to MRI using an FDA-approved SPIO contrast agent. This could be useful for stem cell tracking in vivo, inflammation imaging, angiography, and cancer imaging. My group has built the first MPI scanner in North America.

PG Foam for High Field MRI Shimming we have developed a new composite material that matches a human's magnetic susceptibility. We use pyrolytic graphite micro-crystals embedded in a comfortable closed cell foam. We plan to use this to improve the main field homogeneity to 1 ppm despite the 9 ppm field inhomogeneity introduced at the air-tissue interface. This is the level of homogeneity needed for fast imaging, and robust detection of breast cancer.

July 20, 2009

Multimodality Imaging of Abdominal Aortic Aneurysms

Monica Dua, MD, Dalman Lab

August 3, 2009

Molecular profiling of tumor angiogenesis with ultrasound

Nirupama Suresh DeshPande, Willmann Lab

Molecular Imaging of Malignant Melanoma Using Peptide and Small Molecule Based PET Probes

Gang Ren, Cheng Lab

Aug 17, 2009

Optogenetics: development and application

Karl Deisseroth, MD, PhD
Associate Professor of Bioengineering and Psychiatry, Stanford University

Aug 24, 2009

Optical Imaging to Guide Surgical Resection of Head and Neck Cancer

Eben Rosenthal, PhD
Julius Hicks Professor of Surgery, University of Alabama at Birmingham

Aug 31, 2009

Molecular Imaging of Cancer Metastases and the Pre-metastatic Niche

Carolyn Anderson, PhD
Washington University School of Medicine, St. Louis, MO

Sept 21, 2009

Imaging metabolic reprogramming in cancer

Nicholas Denko, MD, PhD
Assistant Professor, Dept. of Radiology Oncology, Stranford

Oct 12, 2009

Raymond Kim, MD
Assoc. Prof., Medicine
Duke University


Nov 9, 2009
Clark Auditorium

John M Canty, Jr, MD



Dec 7, 2009
Clark Auditorium

Robert Jeraj



Sponsored by: Molecular Imaging Program at Stanford (MIPS) (mips.stanford.edu);
Host: Director, Sanjiv Sam Gambhir, MD, PhD (sgambhir@stanford.edu)

If you would like to be included on the MIPS email distribution list for weekly meeting reminders, contact Susan Singh.


Molecular Imaging