Our Science Initiatives – Diagnostic Imaging
 (Dr. Peter Choyke, Molecular Imaging Program) |
Imaging plays a major role in cancer detection and treatment. Recognizing this, the Center for Cancer Research (CCR) actively invests in clinical and basic imaging research. The CCR supports investigation in advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT), and optical techniques. The CCR has initiated a Molecular Imaging Program that includes the development and testing of tissue-specific MRI, PET, radionuclide, and optical imaging probes for the detection of cancer.
Facilities
The Molecular Imaging Program designs, develops and tests novel targeted imaging probes for the detection and characterization of cancer. The Molecular Imaging Program is closely aligned with the Radioimmune and Inorganic Chemistry Section of the Radiation Oncology Branch. Facilities include hot and cold synthetic chemistry labs, cell culture and biodistribution, physics and image processing support, optical imaging, and animal care facilities. The Molecular Imaging Program sponsors trainees with a broad range of experience.
CCR researchers have access to a variety of state-of-the-art imaging equipment. Clinical facilities in the Clinical Center’s Imaging Sciences Program include the Diagnostic Radiology Department, Nuclear Medicine and PET Department, and the In Vivo Nuclear Magnetic Resonance (NMR) Center, which houses human and animal MR units ranging in field strength from 1.5 to 7 tesla. The PET department consists of three onsite cyclotrons, three whole-body PET scanners, and a PET-CT scanner. The Clinical Image Processing Service provides image analysis and display, and an electronic picture archive and retrieval system (PACS) distributes images.
Currently under installation are an interventional MR unit in the operating room and a research MRI scanner reserved for CCR research.
Animal imaging facilities include the Mouse Imaging Facility, a shared NIH resource containing MRI, CT, ultrasound, and optical imaging devices available to CCR researchers. A micro PET–CT is also available, and a second unit will soon be added.
Clinical Research
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE–MRI)
To Evaluate Tumor Angiogenesis
DCE–MRI is a method for assessing tumor angiogenesis and response to
directed therapy. DCE–MRI involves injecting an MR contrast agent while
imaging is performed. The resulting images are analyzed using pharmacokinetic
models that yield indices of vessel permeability and extracellular or vascular
volume. The results are displayed as color maps (Figure 1). DCE–MRI
has been used in experimental treatment trials, including breast cancer,
prostate cancer, liver and colon cancer, brain tumors, and bone tumors (Figure
2). Research is ongoing to optimize methods of analyzing, displaying, and
interpreting results. Lead investigator: Peter Choyke, MD, Molecular Imaging Program, 301-435-4046.
MR-Guided Prostate Cancer Treatment Using MRI
Prostate cancer is notoriously difficult to image. CCR imaging research focuses
on using MRI to guide prostate cancer treatment more accurately than is
currently possible with the existing techniques. Methods have been developed
to biopsy and place fiducial markers (seeds) in the prostate under MR guidance
in a standard closed 1.5T and 3.0T MRI unit (Figure 3). Research to improve prostate
cancer localization is also being conducted to aid in prostate cancer therapy,
including the following:
High-Resolution MR of prostate. In order to improve the detection and localization of prostate cancer, MRI scans are performed at 3T using high-resolution T2 weighted scans, MR spectroscopy, and dynamic contrast-enhanced MRI. This research is directed at improving the localization of prostate cancer to permit more directed therapy at the cancer, thus minimizing side effects of treatment. This protocol coordinates with other treatment protocols listed below. For more information contact: Yolanda McKinney, RN, NIH Clinical Center.
MR-guided high-dose-rate brachytherapy. Catheters are placed in the prostate gland under MRI guidance and are used to deliver radiotherapy directly to the prostate while minimizing exposure to regions outside the prostate. Very high doses of radioactivity can thus be directed at the tumor while reducing side effects. This can only be achieved by accurate localization of the catheters by MRI (Figure 4). For more information, contact: Anu Singh, MD, Radiation Oncology Branch, 301-496-5457.
MR in evaluating laparoscopic prostatectomy. Laparascopic surgery is a minimally invasive surgical alternative for prostate cancer that offers faster recovery and fewer side effects. MRI scans are obtained prior to laparoscopic surgery to localize the tumor and ensure that the procedure is appropriate (Figure 5). The prostate specimen is then carefully compared with the MRI findings to improve the technique. Laparoscopic prostatectomy results in a few small incisions in the abdomen. For more information contact: Peter Pinto, MD or Jonathan Coleman, MD, Urologic Oncology Branch, 301-496-6353.
Ultrasound in Evaluating Premenopausal Women on Raloxifene
This study is designed to assess the effects of raloxifene, a drug that is used to reduce the risk of breast cancer in high-risk women and that has
been used to prevent breast cancer relapse. Long-term raloxifene use may affect the uterus and ovaries, however, and this study is designed to assess
these effects on women by using transvaginal ultrasound. Endometrial biopsies are obtained from abnormal areas (Figure 5u). This study will improve understanding
of the long-term effects of this class of drugs on the uterus and ovaries.
For more information, contact Ahalya Premkumar, MD, NIH Clinical Center.
PET–CT for Evaluating Cancer
PET is a highly sensitive modality for cancer detection but has limited resolution.
CT has excellent resolution but is not as sensitive for cancer. Combined
in a single unit, the PET–CT offers the best of both worlds. Many
CCR studies involve the use of PET–CT (Figure 6). For instance, PET–CT
can be used to track lymphoma status in patients. In addition to conventional
PET, which uses fluorodeoxyglucose (FDG), other PET agents are available
for clinical trials, including radiolabeled water (Figure 7), carbon monoxide,
and numerous experimental PET agents.
Animal Imaging
Dendrimer-Based MR Contrast Agents for Sentinel Lymph Nodes
The sentinel lymph node concept has reduced the need for radical node
dissections. A new dendrimer-based contrast agent has been developed
that demonstrates
the sentinel lymph node using MRI and optical methods in experimental
animals (Figure 8). Lead
investigator: Hisataka Kobayashi, Molecular Imaging Program, 301-435-8344.
Integrin-Targeted Nanoparticles for MRI Imaging of Angiogenesis
A characteristic of angiogenic vessels is overexpression of integrins. MRI-loaded
nanoparticles that bind to integrins have been developed and are being
tested. If successful, these particles could carry a payload of a therapeutic
agent to treat tumor angiogenesis. Lead investigator: Peter Choyke, MD.
Optical Imaging of Metastases
Optical imaging is a low-cost method of monitoring tumor growth and spread.
Using tumors transfected with green fluorescent protein, or luciferase,
tumors can be monitored noninvasively in a relatively simple light box.
For instance, a colon cancer cell line injected intraperitoneally in a
mouse can be monitored with optical imaging to determine common patterns
and sequences of spread and response to treatment without having to sacrifice
an animal at each time point (Figure 9). Lead investigator: Steve Libutti, MD, Surgery Branch, 301-496-5049.
Imaging of Anti-HER2/neu Monoclonal Antibodies
Many breast cancers express the marker HER2/neu on their cell surfaces, making
HER2/neu a potential target for imaging and therapy. In this work, Herceptin®,
a murine anti-HER2/neu monoclonal antibody, was conjugated with a linker
labeled with indium-111, a radiotracer (Figure 10). Using this agent, researchers
detected implanted human breast tumors in mice. The agent could become
a method for targeting breast cancer for imaging and therapy. Lead investigator: Martin Brechbiel, PhD, Radiation Oncology Branch.
Targeted Imaging of Prostate Cancer
Prostate cancers are notoriously difficult to detect even using high-resolution
MRI methods. This research focuses on the discovery of new targeted
imaging probes based on optical, radionuclide/PET and MRI methods for
identifying cancers within the gland and at metastatic sites. Monoclonal
antibodies and aptamers directed against prostate-specific membrane
antigen (PSMA) are being tested in mice with potential application
to humans. Lead Investigator: Peter
Choyke, MD.
