Project title NMR receptor imaging

cause functional lymphatic abnormalities detectable my MR imaging, before changes in morphology or size become apparent. Examples of such functional abnormalities include altered intranodal lymphatic fluid flow due to micrometastases in the sinuses, or increased neovascular permeability and blood flow. Using genetically engineered tumor ceils, radiotracer studies and compartmental analysis we will now directly correlate nodal tumor burden with LCDIO accumulation. Combined with cell biology studies on cellular uptake into different nodal populations a more complete picture of LCDIO transport to lymph nodes and its magnetic effects will be obtained. The approach will be validated in human lymph nodes using MR imaging, immunohistochemistry against the dextran coat of LCDIO and correlative analysis. The latter studies are especially are especially relevant since little data exists on nodal LCDIO distribution and correlative histology in human lymph nodes. By providing a quantitative assessment of LCDIO transport to lymph nodes. By providing a quantitative assessment of LCDIO transport to lymph nodes this research should enhance the non-invasive characterization of nodal status in patients with known primary cancers and may ultimately aid in the design of novel therapeutic lymphotropic drug carriers. Thesaurus Terms: contrast media, lymph node neoplasm, magnetic resonance imaging, metastasis, neoplasm/cancer classification/staging disease model, iron oxide, neoplasm / cancer pharmacology, neoplastic cell, neoplastic growth bioimaging/biomedical imaging, human tissue, immunocytochemistry, laboratory mouse, lymph node, lymphadenectomy, radiotracer

Institution:

Fiscal Year: Department: Project Start: Project End: Icd: IRG:

Massachusetts General Hospital 55 Fruit St Boston, MA 02114 1999 01'Apt-93 28-Feb-02 National Cancer Institute RNM

protein receptors on hepatocytes and to cholecystokinin (CCK) receptors on pancreas cells and demonstrated improved differentiation of benign and malignant lesions (MR receptor imaging). In the current Project we propose to a) complete the investigations of MR receptor imaging of the pancreas and b) to extend previous research to antigenic and/or receptor sites present on malignant cells. W e p r e s ent data on magnetoimmunoconjugates based on a monocrystalline iron oxide nanocompound (MION) including studies to optimized our coupling strategies and showed that most of the antibody affinity can be retained through conjugation. The proposed research expands on successful in vivo cell culture experiments and in vivo MR imaging with such antibody MION conjugates directed to tumor cell surface structures (MION-L6) or internalized compartments (MION-BR96). We anticipate that results, models and conjugation technology from this research can be used to assess cell surface structure in a variety of neoplastic systems (breast cancer, lung cancer, pelvic malignancies, lymphoma etc.) MR imaging of tumor antigens is expected 'to allow in vivo typing of malignant tissues, to enhance detection of cancer and to predict efficacy of immunotherapy with chemoconjugates and immunotoxins. Thesaurus Terms: contrast media, diagnosis design/evaluation, magnetic resonance imaging, neoplasm/cancer diagnosis, receptor carbohydrate receptor, cell membrane, chemical conjugate, histology, immunoconjugate, iron oxa ide, membrane structure, neoplastic growth, nuclear magnetic resonance spectroscopy, pancreas neoplasm, pharmacokinetics laboratory rat

Institution:

Fiscal Year: Department: Project Start: Project End: ICD: IRG:

Massachusetts General Hospital 55 Fruit St Boston, MA 02114 1999 05-Jan-89 31-Mar-02 National Cancer Institute NCI

3ROJECT TITLE

~ROJECT TITL[ NMR RECEPTOR IMAGING Grant Number: PI Name:

5P01CA48729-110005 Weissleder, Ralph

Abstract: The goal of this research is to extend our previ-

ous magnetic resonance (MR) receptor imaging research and develop novel immunospecific contrast agents for the in vivo characterization of cancer. These agents ideally act as ~molecular probes~ for cell surface structures either in normal tissue or in tumor tissue. During the previous funding period, we have successfully synthesized and directed superparamagnetic magnetoconjugates to asialoglyco-

386

TARGETED METAL CHELATORS FOR DIAGNOSTIC IMAGING Grant Number: PI Name:

5R01CA42925-12 Welch, Michael J.

Abstract: Metal radionuclides are widely used in diagnostic

imaging. Radioisotopes of gallium, indium, technetium and copper are used in nuclear medicine studies while gadolinium chelates act as paramagnetic contrast agents in conjunction with nuclear magnetic resonance imaging (MRt). New improved chelating agents for these metal ions have been designed.