The goal of this proposal is to address hypotheses regarding the imaging and therapy of cancer, in particular the targeting of the process of cancer metastasis with 64Cu-labeled peptides that target the avB3 integrin. The process of cancer metastasizing to the bone has been shown to be highly dependent on the presence of integrins, in particular the B3 integrin. Developing a bone imaging agent which specifically targets the avB3 integrin will allow clinicians to discriminately target sites of bone metastasis and would permit them to better determine the efficacy of a patient's treatment and plan additional therapy as needed.
The specific aims, in brief, are (1) to develop 64Cu-CB-ligand conjugated peptides which possess enhanced in vivo stability. (2) Use micro PET imaging in conjunction with in vitro analysis to determine the binding affinity of these 64Cu-Cbligand conjugated peptides for the avB3 integrin, and to evaluate the use of the radiopharmaceuticals as PET bone metastasis imaging agents; and (3) to evaluate these 64Cu-CB-ligand conjugated peptides as therapeutic agents for bone metastasis.
|Zheleznyak, Alexander; Wadas, Thaddeus J; Sherman, Christopher D et al. (2012) Integrin ?(v)?? as a PET imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation. Mol Imaging Biol 14:500-8|
|Shokeen, Monica; Wadas, Thaddeus J (2011) The development of copper radiopharmaceuticals for imaging and therapy. Med Chem 7:413-29|
|Odendaal, Antoinette Y; Fiamengo, Ashley L; Ferdani, Riccardo et al. (2011) Isomeric trimethylene and ethylene pendant-armed cross-bridged tetraazamacrocycles and in vitro/in vivo comparisions of their copper(II) complexes. Inorg Chem 50:3078-86|
|Wadas, Thaddeus J; Wong, Edward H; Weisman, Gary R et al. (2010) Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease. Chem Rev 110:2858-902|
|Barnard, Peter J; Holland, Jason P; Bayly, Simon R et al. (2009) Macrocyclic diamide ligand systems: potential chelators for 64Cu- and 68Ga-based positron emission tomography imaging agents. Inorg Chem 48:7117-26|
|Wadas, Thaddeus J; Deng, Hongju; Sprague, Jennifer E et al. (2009) Targeting the alphavbeta3 integrin for small-animal PET/CT of osteolytic bone metastases. J Nucl Med 50:1873-80|
|Wadas, Thaddeus J; Eiblmaier, Martin; Zheleznyak, Alexander et al. (2008) Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors. J Nucl Med 49:1819-27|
|Anderson, C J; Wadas, T J; Wong, E H et al. (2008) Cross-bridged macrocyclic chelators for stable complexation of copper radionuclides for PET imaging. Q J Nucl Med Mol Imaging 52:185-92|
|Heroux, Katie J; Woodin, Katrina S; Tranchemontagne, David J et al. (2007) The long and short of it: the influence of N-carboxyethyl versusN-carboxymethyl pendant arms on in vitro and in vivo behavior of copper complexes of cross-bridged tetraamine macrocycles. Dalton Trans :2150-62|
|Wadas, T J; Wong, E H; Weisman, G R et al. (2007) Copper chelation chemistry and its role in copper radiopharmaceuticals. Curr Pharm Des 13:3-16|
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