2007 MIPS Molecular Imaging Seminar Series

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

January 8, 2007

Michael E. Phelps, PhD 
Norton Simon Professor
Chair, Department of Molecular & Medical Pharmacology 
Director, CIMI 

Molecular Imaging Diagnostics with PET: A new biomarker discovery pathway from cancer biology to patients. 

Molecular Imaging Diagnostics with PET: A new biomarker discovery pathway from cancer biology to patients Molecular Imaging diagnostics (MID) with PET consist of an imaging instrument and labeled molecules with properly formulated tracer or pharmacokinetic models representing transport and reactions of the labeled molecule to provide assays of biological, biochemical or pharmacologic processes or to track cells or particles (e.g., nano, viral, etc). These assays provide diagnostic biomarkers of disease, stratification of patients by therapeutic target and assessment of therapeutic efficacy, as well as guiding the drug discovery and development processes. The greatest progress in MID with PET will be in biomarkers and molecular technologies, even through innovation in PET imaging instruments continue. 

The goal of this research is to create a novel PET biomarker discover pathway from basic science to patients with a primary focus on cancer. Enabling technologies are being developed along this pathway to accelerate the discovery rate, increase diversity and lower costs to synthesize, validate and use PET biomarkers for MID, as well as to increase availability of MID biomarkers to academic and industry (imaging & pharmaceutical) and clinical diagnostics. A critical step in this process is to get the biology of cancer right – develop a knowledge base of the modules (e.g., apoptosis, cell cycle, angiogenesis, etc.) transitioning (re-programming) normal cells to malignant properties and identify critical, controlling mutated proteins in theses transitions as molecular imaging and drug targets. 

Studies will be shown to demonstrate the use of biological measures with PET to detect, stage and separate treatment responders from non-responders – both after short-term therapy and by whether patients have or do not have the drug target prior to treatment. Integrated microfluidic chips are being developed to synthesize, label and measure the biochemical properties of PET biomarkers. A software package, Kinetics Imaging System (KIS) is employed to convert the kinetics of data collected into information – biochemical assays, pharmacokinetics, etc. In vivo and in vitro molecular diagnostics need to become a measurement science.

January 22, 2007

Imaging RNA with Spliceosome-Mediated Trans-Splicing
Zac Walls, Gambhir Lab

Nanoparticle-Based Tumor Targeting and Imaging
Weibo Cai, PhD, Chen Lab

January 29, 2007

Production of radionuclides - The chemistry starts here
David Dick, PhD, Head of Cyclotron Physics

February 5, 2007
Clark Auditorium

Dean W. Felsher, MD, PhD
Associate Professor
Division of Oncology 

Imaging the Death and Resurrection of Cancer 


February 12, 2007
Clark Auditorium

David R. Piwnica-Worms, MD, PhD
Professor, Molecular Biology & Pharmacology
Washington University

Spectral Deconvolution of Multi-Color Reporters for Imaging Signal Transduction Pathways in Real Time 

Genetically-encoded imaging reporters introduced into cells and transgenic animals enable noninvasive, longitudinal studies of dynamic biological processes in intact cells and living animals. A wide variety of bioluminescent luciferase proteins are available and when engineered into fusion proteins rather than cloned into promoter/enhancer sequences, these imaging reporters enable fundamental processes such as post-translational modification, signal transduction cascades, protein-protein interactions, oncogenic transformation, and targeted drug action to be temporally and spatially registered in vivo in real time. Furthermore, multi-color post-translational reporters can be simultaneously imaged to deconvolute signals such as normalized IkB kinase activity in longitudinal assays. These reporters provide a rapid, simple, and accurate method for simultaneously measuring multiple bioluminescent reporters in living cells and may provide new contextual insight into cell-specific molecular and regulatory machinery.

February 26, 2007

Imaging a Viral-Enhanced Immunotherapy for the Treatment of Cancer
Steve Thorne, PhD, Contag Lab
64Cu-Labeled Tetrameric and Octameric RGD Peptides for microPET Imaging of Tumor avb3 Integrin Expression
Zibo Li, PhD, Chen Lab

March 5, 2007

Clinical Projects in Molecular Imaging
Andrew Quon, PhD, Assistant Professor of Radiology
Fellowship Director, Nuclear Medicine Division

March 12, 2007
Clark Auditorium

Victor W. Pike, PhD,
Molecular Imaging Branch (MIB)
NIMH, Bethesda, MD

Discovery of Radioligands for Human Brain Imaging with PET In Vivo-Craft or Science?
The physical, chemical and biological basis of positron emission tomography (PET) as a molecular imaging modality in neuropsychiatric research will be briefly described, leading into a discussion of the properties desired in candidate radioligands for PET imaging of brain proteins (e.g. neurotransmitter receptors and transporters). These properties, their assessment and predictability, will be discussed and exemplified with results from established and new PET radioligands.

March 19, 2007

Clinical Projects in Molecular Imaging
Michael Mcconnell, MD
Director, Cardiovascular MRI Program, Department of Medicine
Associate Director, Cardiovascular Medicine Fellowship Program
Associate Professor, Cardiovascular Medicine, Electrical Engineering (by courtesy), and Molecular and Cellular Physiology (by courtesy)

March 26, 2007

In Vivo Imaging of Beta-lactamase Activity
Hequan Yao, PhD, Rao Lab

Cytokine-Induced Killer Cell Biology: Chemokine-Directed Trafficking to Tumors
Tobi Schmidt, Contag Lab

April 2, 2007

Metabolic Imaging using Hyperpolarized MR agents
Daniel Spielman, PhD
Associate Professor of Radiology (Diagnostic Radiology) and, by courtesy, of Electrical Engineering

April 9, 2007
Clark Auditorium

Brian W. Pogue, PhD 
Assoc. Prof.
Thayer School of Engineering

MRI-guided Near-infrared Spectroscopy of Breast Cancer in vivo 

Integration of Near-Infrared Spectroscopy (NIRS) into standard medical imaging instrumentation has been slow in developing, yet today there have been major developments which make it achievable on a routine basis. NIRS is combined with Image-guided recovery of the tissue components, using standard MR images, to quantify the spectroscopic features of breast cancer. A prototype system integrating NIRS into a 3T MR breast coil is outlined, and the initial approach to using the MR image as the template upon with spectroscopy is completed are discussed.

The detector scheme for MR or CT-guided NIR is perhaps the most complicated decision for integration, as most useful choices take optical spectroscopy out of the "inexpensive" category. Two prototype systems for frequency domain and broadband spectral imaging of tissue are discussed, and it is shown that the spectral tomography system is ideal for fluorescence or bioluminescence tomography in vivo. This type of hybrid imaging is still in its infancy, yet using it to guide therapy or to properly individualize therapy choice is the next logical step. Use of MRI or CT as the backbone technology to exploit NIRS is a logical step for integration of this modality into clinical use.

At the small animal imaging, much more can be achieved, and the combination of 3T MR with NIRS for small animal studies is also discussed. Molecular tracers such as Epidermal Growth Factor and Protoporphyrin IX are shown to be increased in glioma models. The use of hybrid imaging systems such as image-guided NIRS is likely to be the next major phase of imaging instrumentation development, as it allows quantification of molecular tracers and biophysical imaging of tissue, using contrast mechanisms which are not otherwise available.

April 16, 2007

PET: Current and emerging applications in radiation therapy
Billy W. Loo Jr., MD, PhD, DABR
Instructor, Department of Radiation Oncology
Thoracic Radiation Oncology Program Leader

April 23, 2007

MRI Applications in Molecular Imaging
Mike Mosely, PhD
Associate Professor of Radiology

April 30, 2007

Targeted Delivery of TNF to avb3 Positive Tumor Enhanced the Anti-tumor Effect of TNF
Hui Wang, PhD, Chen Lab

MicroPET Imaging of Urokinase-type Plasminogen Activator Receptor Expression Using 64Cu-Labeled Peptides
Gang Niu, PhD, Chen Lab

May 7, 2007

Image Analysis and Quantitation for Lung Cancer Imaging: From Bedside to Bench
David Paik, PhD
Assistant Professor, Radiology-Diagnostic Radiology

May 14, 2007
Clark Auditorium

Julie L. Herberg, PhD
Physicist, Lawrence Livermore Nat'l Lab

Stretching the limits of MRI through development of microcoil technology and novel contrast agents for molecular imaging.

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) have been extensively used for chemical, material, biological, and medical applications. Our group at Lawrence Livermore National Laboratory (LLNL) has used Magnetic Resonance Microscopy (MRM) to examine a variety of materials, including polymeric materials and biofilms. During the first part of this Seminar, I will discuss the advantages and limitations of using MRM techniques for analyzing these types of materials. In addition, I will discuss how commercial MRM systems are not well suited for the analysis of very small volumes (on the order of 10 m3 volume element of an MR image) due to the inherent lack of sensitivity of MRI (often greater than g/ml limit of detection). To address the issue of sensitivity of the MRM system, I will discuss our development of rf microcoils, which inherently have large sample filling factors and efficient coupling of the excitation and detection radio frequencies to the sample. LLNL has developed a fabrication methodology suited for development and construction of any desired geometry microcoils with laser lithography. These small NMR coils of various geometries can be prepared to exact specification on curved surfaces with micron level feature sizes. Lithographical techniques can produce rf microcoils, shim coils, and gradient coils. Currently, we are using the rf microcoils to develop a portable microcoil NMR system that consists of a hand-held 450g magnet and an RF probe with laser-fabricated microcoils, which are integrated into a tabletop system. Such a system is ideal for chemical identification of trace substances in the field. Similar principles can be extended to develop highly sensitive MRM for molecular imaging. This technology could eventually lead to a portable MRM system.

The second part of this Seminar will discuss a new type of MRI contrast agent that can provide brighter and more physiologically relevant MR images than the current state-of-the-art in MRI. The MRI contrast agents that we are investigating could target and highlight specific types of tissues and would be highly beneficial for both detection and therapy of cancer. Attachment of a Gd3+ contrast agent, Gd-DOTA, and an antibody targeting mechanism to a water-soluble silica coated quantum dot may allow for tissue specific contrast. Results will be presented to demonstrate that Gd-DOTA attached to quantum dot displays a greater contrast to traditional, non-specific contrast agents. In addition, I will discuss the advantages of our approach, including greater relaxivity and greater simplicity of the synthesis process.

Both the development of lithographically produced microcoils and nanoparticles coated with a water-soluble thin silica shell doped with paramagnetic Gd3+ ions attach allow for flexibility in MRM and MRI that will provide a basis for new developments in this field. This work was performed under the auspices of the U.S. Department of Energy by the University of California Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48

May 21, 2007

Stanford Radiology 3D Lab: Clinical and Research Highlights
Sandy Napel, PhD
Associate Professor of Radiology
Co-Director, 3D Medical Imaging Laboratory
Associate Member, MIPS

June 4, 2007

4:30-5pm Reception
5-5:45pm Seminar
5:45-6pm Q&A

In Vivo evolution of ribozyme
Hui Wang, PhD, Chen Lab

Fluorescent labeling of RNA using small-molecular probes
Anca Dragulescu-Andrasi, Ph.D., Rao Lab

June 11, 2007
Clark Auditorium

Bruce J. Tromberg, PhD
Laser Microbeam and Medical Program,
Beckman Laser Institute and Medical Clinic,

Medical Imaging in Thick Tissues Using Diffuse Optics
Medical diagnostic techniques based on near infrared (NIR) transillumination were first introduced more than 70 years ago to detect breast cancer. Although NIR light penetrates tissue to depths of several centimeters, early methods were not successful due to the fact that these approaches were qualitative and did not account for distortions from multiple light scattering.

Recent advances in temporal- and spatial- frequency-domain "photon migration" now make it possible to separate light absorption from scattering in thick tissues. Temporal frequency-domain methods measure the phase shift and amplitude of MHz - GHz intensity-modulated waves (1), while spatial frequency-domain techniques utilize structured light patterns to form wide-field images of tissue optical properties (2). Both approaches are based on comparing measured data with radiative transport models to form images, i.e. "diffuse optical imaging (DOI)", and acquire spectra, i.e. "diffuse optical spectroscopy (DOS)".

This talk reviews principles of light propagation in tissue and describes the development of DOI/DOS for non-invasively characterizing tissue structure and biochemical composition. Particular emphasis is placed on the development of broadband methods for quantitative, high-resolution measurements of NIR absorption and scattering spectra between 600-1000 nm (3). These data are used to determine the tissue concentration of deoxygenated hemoglobin, oxygenated hemoglobin, methemoglobin, lipid, and water, as well as the tissue "scatter power". Clinical study results are shown highlighting the sensitivity of broadband DOS to metabolic changes in breast cancer detection and therapeutic drug monitoring (4,5). Broadband spatial frequency-domain imaging is used in pre-clinical animal models to dynamically map intrinsic brain signals and monitor the efficacy of chemotherapeutic agents. These findings will be placed in the context of conventional imaging methods, such as MRI, in order to assess the current and future role of diffuse optics in medical imaging (6).

June 18, 2007

Clark S360

Image Guidance During Interventional Procedures: Beyond Fluoroscopy
Rebecca Fahrig, PhD
Assistant Professor, Department of Radiology

June 25, 2007

Protein modifications that regulate oxygen sensing and tumor angiogenesis
Amato Giaccia, PhD
Professor & Director, Division of Radiation and Cancer Biology
Department of Radiation Oncology
Stanford University School of Medicine

July 9, 2007
Clark Auditorium

Daniel B. Vigneron, PhD 
Professor, Radiology, UCSF

Application of Hyperpolarized Carbon-13 MR Metabolic Imaging for Prostate Cancer Research 

Carbon-13 MRS of labeled substrates has the potential to improve the characterization of prostate cancer based on known changes in metabolic fluxes through glycolysis, the citric acid cycle and fatty acid synthesis. To study this 13C metabolism in vivo, we have applied an exciting new advance in metabolic imaging, hyperpolarized 13C MR described by Ardenkjaer-Larsen JH, et al. Using this method, 50,000+ fold signal enhancement allows in vivo detection of a 13C hyperpolarized compound such as pyruvate and its metabolic products following injection. We applied this method to study transgenic mouse models of prostate cancer. Using a 15 second 3D MRSI sequence, we have observed rapid uptake of pre-polarized 13C-pyruvate in vivo and its metabolism to 13C labeled lactate in primary and metastatic tumors. Significantly higher 13C-lactate levels were detected in tumors as compared to normal tissues. 

July 16, 2007

Recent advances in computed tomography
Norbert Pelc, PhD

July 23, 2007

Functional Neuroimaging - a Biomarker?
Gary Glover, PhD

July 30, 2007

Ribozyme Mediated Imaging of mRNA-update
Gayatri Gowrishankar, PhD, Rao Lab

Studying Drug Modulated Multi-protein Interactions by Split Reporters
Paul Ramasamy, PhD, Gambhir Lab

August 6, 2007

A site-specific integration system for non-viral gene therapy
Michele Calos, PhD

August 13, 2007
Clark Auditorium

Jeff W. Lichtman
Professor, Molecular & Cellular Biology


August 20, 2007

Imaging prodrug conversion in an effective cancer therapy using a new drug and evolved enzymes
A.C. Matin, PhD

August 27, 2007

18F-labeled Proteins as Probes for Positron Emission Tomography (PET)
Mohammad Namavari, PhD

September 10, 2007

Imaging brain hemodynamics and oxygenation in patients with cerebrovascular disease
Greg Zaharchuk, PhD

September 17, 2007
Clark Auditorium

Xiaoliang Sunney Xie, PhD
Prof. of Chemistry
Harvard University

Single-molecule Imaging of Transcription, Translation and Replication in Living Cells; and Vibrational Imaging of metabolites and Drugs in Living Organisms
The combination of specific probes and advanced microscopy allows detecting and tracking a particular protein with single-molecule sensitivity, nanometer spatial precision, and millisecond time resolution in living bacterial cells. This yields quantitative information regarding many fundamental processes in molecular biology. Metabolites and drugs, usually difficult to detect, can be imaged and monitored in living organisms with coherent anti-Stokes Raman scattering (CARS) microscopy that requires no fluorescence labels, and offers extremely high sensitivity.

September 24, 2007

Accelerating tomographic image reconstruction for positron emission tomography using computer graphics hardware
Guillem Pratx, Levin Lab
Site specific conjugation of proteins to quantum dots
Zuyong Xia, Ph.D., Rao Lab

October 1, 2007

Nanoplatforms for molecular imaging and therapy
Xiaoyuan (Shawn) Chen, PhD

October 8, 200
Clark Auditorium

Martin G. Pomper, MD, PhD
Assoc. Prof. of Radiology
Johns Hopkins University

Translational Molecular Imaging for Oncology

Although most clinical diagnostic imaging studies employ anatomic techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, much of radiology research currently focuses on adapting these conventional methods to physiologic imaging as well as on introducing new techniques and probes for studying processes at the cellular and molecular levels in vivo, i.e. molecular imaging. Molecular imaging promises to provide new methods for the detection of minimal changes in diseased tissue and support for personalized therapy. Although molecular imaging has been practiced in various incarnations for over 20 years in the context of nuclear medicine, other imaging modalities have only recently been applied to the noninvasive assessment of physiology and molecular events. Nevertheless, there has been sufficient experience with specifically targeted contrast agents and high-resolution techniques for MR imaging and other modalities that we must begin moving these new technologies from the laboratory to the clinic. Several projects relevant to oncology will be discussed with emphasis on how they were/will be moved from the bench to the clinic.

October 15, 2007

Monitoring Stem Cell Fate by Bioluminescence Imaging
Helen Blau, PhD
The Donald E. and Delia B. Baxter Professor of Pharmacology and Professor of Chemical and Systems Biology

October 22, 2007

Screening for Cancer: Does Early Detection Save Lives?
Sylvia Plevritis, PhD

October 29, 2007

Glycobiology at the cell surface
Jennifer Prescher, PhD, SMIS Fellow

Qdot Conjugates for in vivo Molecular Imaging
Min-Kyung So, PhD, Rao Lab

November 5, 2007
Clark Auditorium

Mina J. Bissell
Lawrence Berkeley Laboratory
Berkeley, CA

The architectural basis of tissue specificity: the relationship between the genome and 3D structure


November 19, 2007

Advanced Imaging of Articular Cartilage: From Morphology to Physiology
Garry Gold, PhD

November 26, 2007

Application of magnetic nanoparticles for multimodality imaging
Ha-Young Lee, Ph.D., Chen Lab

18F Labeling of Biomolecules Using Anionic Fluoride in an Aqueous Environment
Christopher Caires, Guccione Lab

December 3, 2007

New technologies to enhance the molecular sensitivity of positron emission tomography
Craig Levin, PhD

December 10, 2007
Clark Auditorium

Anna Wu, PhD
Professor, Department of Molecular & Medical Pharmacology
Associate Director, CIMI

Antibodies and Antimatter: ImmunoPET for Imaging Cancer

January 3, 2008

Predicting tumor response to targeted therapy from non-invasive imaging
Jill Lin, Paik Lab

In vivo imaging of embryonic stem cell transplantation immunobiology
Rutger-Jan Swijnenburg, PhD, Wu Lab

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.