Projects Approved October 2000
PreClinical and Correlative Imaging of Tumor Angiogenesis
Mark D. Bednarski, Ph.D., Targasome, Inc.
Summary: The agent is a recently developed molecular imaging technology using a paramagnetic particle targeted toward a cell surface receptor upregulated during the process of tumor angiogenesis. The method uses the human monoclonal antibody, Vitaxin 2, conjugated to polymerized vesicles (V2-PV) labeled with gadolinium ions that bind to the endothelial marker αvβ3 (V2-PV-Gd).
Pre-Clinical Testing of F-18 Fluorocholine
Timothy R. DeGrado, Ph.D., Duke University
Summary: The aim of the project is to develop [18F]fluorocholine (FCH) for detection and localization of cancer using positron emission tomography (PET). The approach is motivated by the findings of elevated choline and choline kinase activity in a variety of cancer types, and recent reports of the utility of [11C]choline in PET studies in prostate carcinoma, brain tumors, and esophageal carcinoma.
Projects Approved September 2002
[F-18]FACBC A Novel Agent for Tumor Imaging by PET
Mark M. Goodman, Ph.D., Emory University
Summary: The objective of this project is to develop a novel fluorine-18 labeled positron emitting alicyclic amino acid, [18F]FACBC, into a clinical project for the diagnostic imaging of human tumors. The movement of amino acids across tumor capillaries is up-regulated in comparison to most normal tissues by carrier-mediated facilitated transport involving both the "L" and "A" amino acid transport systems.
MRI Detection of Angiogensis with αvβ3-Nanoparticles
Gregory M. Lanza, M.D., Ph.D., Washington University
Summary: The subject of this research is the preclinical development of a novel, paramagnetic, targeted contrast agent for magnetic resonance imaging of the αvβ3-integrin expressed by neovascular vessels associated with solid tumors.
Cu-ATSM: Preclinical Development via the DCIDE Program
Jason S. Lewis, Ph.D., Washington University
Summary: Cu-ATSM, labeled with a radioisotope of copper, Cu-64, will have a significant clinical impact for both the imaging of hypoxia and the radiotherapy of cancer. The supporting evidence demonstrates that this compound has rapid uptake for hypoxic tissue for use as an imaging agent and is also effective in treating tumor burdens as a therapeutic agent.
Safety Testing and Toxicology Reports for Cu-ATSM
Preclinical Toxicology Summary
Rabbits: 14-Day Toxicity Study
Rats: 14-Day Toxicity Study
Beagle Dogs: Cardiovascular & Pulmonary Safety Testing
Salmonella Reverse Mutation: Potential Mutagenic Activity
Mouse Lymphoma Assay: Potential Mutagenic Activity
Pharmacology and Toxicology of F-19-Galacto-RGD
Markus Schwaiger, M.D., Technische Universitat Munchen
Summary: The integrin αvβ3 plays an important role in several diseases such as tumor cell metastasis, angiogenesis and inflammation. Galacto-RGD is a recently developed glycosylated cyclic pentapeptide (c(Arg-Gly-Asp-D-Phe-Lys(SAA)) with selective, high-affinity binding to αvβ3. Radiolabeled F-18-Galacto-RGD and positron emission tomography (PET) have been successfully used in animal models to image αvβ3 expression in xenotransplanted tumors as well as in chronic inflammatory processes.