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 b+ particles for positron emission tomography (PET) imaging and b- 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. These studies are being performed to understand mechanisms of localization of 64Cu into the tumor cell nucleus and how this affects cell killing. 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 integrin ligands for targeting bone metastases.
Selected Publications:
Shokeen M, Anderson CJ. Molecular imaging of cancer with copper Radiopharmaceuticals and positron emission tomography (PET). Acc Chem Res 2009 42: 832-841.
Almutairi A, Rossin R, Shokeen M, et al.. Biodegradable dendritic positron emitting nanoprobes for the non invasive imaging of angiogenesis. Proc Nat Acad Sci USA 2009 106: 685-690.
Eiblmaier M, Meyer LA, Watson MA, Fracasso PM, Pike LJ, Anderson CJ. Correlating EGFR expression with receptor binding properties and internalization of 64Cu-DOTA-C225 in five cervical cancer cell lines. J Nucl Med 2008 49: 1472-1479.
Eiblmaier M, Meyer LA, Anderson CJ. The Role of p53 in the Trafficking of Copper-64 to Tumor Cell Nuclei. Cancer Biol Ther 2008 7: 63-69.
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.
Last Updated: 08/12/2009 |