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Molecular Imaging Program

Research

The goal of the Molecular Imaging Program (MIP) is to develop targeted imaging methods that accelerate the development of cancer therapies.

The Molecular Imaging Program (MIP) was established in 2004. The MIP is focused on the development of in vivo imaging agents targeted to cancer for early detection and monitoring. The explosion of available molecular targets for therapy has been accompanied by similar opportunities in diagnostic imaging, however, the role of imaging biomarkers in cancer diagnosis and therapy monitoring is still controversial. Given the high risks and high costs of conducting research in this field, the Molecular Imaging Program is well positioned to answer some of these questions on behalf of the oncology community.

The MIP has three sections: A Molecular Imaging Clinic for human imaging, a Pre-clinical Imaging Section and a Physics Section.

The Molecular Imaging Clinic, which opened in 2009, is located in Building 10 on the main Bethesda campus of NIH. Here, we investigate potential diagnostic imaging agents that employ nuclear, optical or magnetic resonance reporters in human subjects. Currently, there are twelve active human procotols which involve the following PET fluorinated agents: FLT, Fluciclitide, Fluciclavine, Paclitaxel, Sodium Fluoride, Estradiol and the following Indium labeled antibodies: Trastuzumab and MORAb-009. Agents under consideration include hypoxia, apoptosis and cytokine markers. In addition to commercial sources, our current internal radiochemistry resources are: the Image Probe Development Center (Gary Griffiths, NHLBI), Frederick NCI (Cancer Imaging Program), PET department (Clinical Center NIH), Radiolabeling facility (Building 21, Clinical Center Chang Paik), Molecular Imaging Probe lab (Shawn Chen, NIBIB).

A special interest of the MIC is prostate cancer. The Molecular Imaging Clinic is a full partner in the Prostate Cancer Multidisciplinary Clinic focusing on MRI, PET and SPECT, for the detection, staging and monitoring of prostate cancer in its various clinical states (from localized to metastatic) in conjunction with the Urologic Oncology Branch, Radiation Oncology Branch, Medicine Branch, Laboratory of Pathology and the Center for Interventional Oncology.

In the preclinical section we are pursuing a variety targeted agents. Optical imaging is a major area of investigation because it is highly sensitive, requiring low cost imaging equipment, and does not expose the patient to ionizing radiation. This effort is led by Dr. Hisataka Kobayashi, MD, PhD. Unlike other imaging modalities, optical probes can be activated at the site of disease. For instance, we have developed an activatable optical contrast agent that only fluoresces when it is activated by gamma-glutaminase, an enzyme highly expressed by some tumors. In a colitis associated colon cancer (CAC) model we have used a mini-endoscope, equipped with a fluorescent camera, to detect tumors less than 1 mm in diameter, many of which are flat and otherwise difficult to detect. We can use similar methods for detecting HPV infection in mouse models. Similarly, in a peritoneal dissemination model of ovarian cancer, this agent detected tiny peritoneal implants. In another approach, a targeting vector (e.g. Herceptin) is conjugated to a non-activated fluorophore or an active fluorophore made inactive by conjugation (dimer formation). Upon internalization at the target lesion, it fluoresces leading to very high target to background ratios (up to 40-fold) making even very tiny foci of cancer highly visible. This holds promise for improving the detection and excision of cancers during endoscopy and surgery. Additionally, we have uncovered a number of activatable fluorophores that produce phototoxic effects on tissue with high light flux. This means that the same agent might be a diagnostic at low flux but become therapeutic at higher energies.

We are developing a variety of radionuclide targeted imaging agents for clinical translation. This effort is led by Elaine Jagoda PhD. Our current portfolio includes imaging agents for c-MET, mesothelin, ACE inhibitors and TEM8 associated with angiogenesis. This work is in collaboration with CCR colleagues who have a deep interest in these targets (Bottaro, Pastan, Eckelman, St Croix respectively). Our preclinical work includes in vitro assays, biodistribution and early therapy studies. We have both microSPECT and microPET scanners for this work. Additionally, we are pursuing cell tracking studies in T lymphocytes to better understand the fate of such cells after immune stimulation and cellular therapies. This work is conducted by Noriko Sato, MD, PhD. In MRI we have designed high sensitivity labeled dendrimers as contrast agents which have been tested in large animals for lymphatic imaging.

The MIP is an example of multidisciplinary team, combining the skills of chemists, physicists, imagers and biologists. Our physicists have built new cameras and devices that improve image quality or validation methods. For instance, MIP physicists designed and built a portable flat panel projection gamma camera for pre-clinical use.

The MIP not only provides imaging expertise to the CCR but encourages specific scientific collaborations within CCR. It is highly cross-disciplinary and highly translational covering imaging physics to pre-clinical to clinical imaging. The research conducted by the MIP is inherently high risk/high impact because of the high costs involved with performing this research. MIP leverages the rich research environment of the CCR to enhance collaborations with basic scientists and clinicians.

This page was last updated on 4/11/2012.