Research Abstract:
The major focus of our research is the development, evaluation and application of radiopharmaceuticals containing metal radionuclides for diagnostic imaging and targeted radiotherapy of cancer. We are particularly interested in 64Cu (T1/2 = 12.7 hours), in large part because it emits Beta+ particles for positron emission tomography (PET) imaging and Beta- particles for radiotherapy. The agents we are studying are 64Cu-labeled bifunctional chelate-receptor ligand conjugates for imaging and therapy of various types of cancer. Somatostatin is a peptide hormone of which certain tumors have upregulated receptors. We are developing new radiolabeled bifunctional-chelator-peptide conjugates of these receptor ligands for PET and radiotherapy. We are also interested in understanding thein vivo metabolism and in vitro subcellular metabolism of these agents. One aspect of these metabolism studies is the correlation of the nature of the bifunctional chelate and the radiometal to differences in the biodistribution of radiometal-chelate-biomolecule conjugates. With collaborators from the University of New Hampshire, we developed cross-bridged macrocyclic chelators for 64Cu that form highly stable complexes in animal models in vivo. The greater in vivo stability of 64Cu-labeled cross-bridged chelator somatostatin conjugates impart signficantly improved uptake in tumors with more rapid clearance from blood and liver compared to 64Cu-labeled somatostatin analogs with less stable chelators. Another major area of research in our lab is the development of imaging agents targeting the process of cancer metastasis. Towards this goal we are investigating radiolabeled inhibitors of matrix metalloproteinases for imaging of tumors to predict metastatic potential and radiolabeled integrin ligands for targeting bone metastases.
Selected Publications:
Eiblmaier M, Andrews R, Laforest R, Rogers BE, Anderson CJ. Nuclear Uptake and Dosimetry of 64Cu-labeled Chelator-Somatostatin Conjugates in a SSTr2-transfected Human Tumor Cell Line. J Nucl Med 2007 48:1390-1396.
Sprague JE, Kitaura H, Zou W, et al. Non-invasive Imaging of Osteoclasts in Parathyroid Hormone-Induced Osteolysis Using a 64Cu-labeled RGD Peptide. J Nucl Med 2007 48:311-318.
Sprague JE, Peng Y, Fiamengo AL, et al. Synthesis, Characterization and in vivo Studies of Cu(II)-64-labeled Cross-bridged Tetraazamacrocycle-amide Complexes as Models of Peptide Conjugate Imaging Agents. J Med Chem 2007 50:2527-2535.
Wadas TJ, Wong EH, Weisman GR, Anderson CJ. Copper chelation chemistry and its role in copper radiopharmaceuticals. Current Pharmaceutical Design 2007 13:3-16.
Wadas TJ, Anderson CJ. Labeling of TETA-and CB-TE2A-conjugated peptides with copper-64. Nature Protocols. 2006 1:3062-3068.
Last Updated: 09/05/2007 |