Anderson's Group

The major focus of our research is the development, evaluation and application of radiopharmaceuticals containing metal radionuclides for diagnostic imaging of disease and targeted radiotherapy. We are particularly interested in ⁶⁴Cu (T_1/2 = 12.7 h), in large part because it emits β+ particles for positron emission tomography (PET) imaging and β- particles for radiotherapy. Our research has focused on ⁶⁴Cu-labeled bifunctional chelate-receptor ligand conjugates for imaging and therapy of disease. The molecular targets we are evaluating include somatostatin, integrins and matrix metalloproteinases. These targets have applications in cancer, as well as heart and lung diseases. We are also interested in understanding the in 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 target tissues with more rapid clearance from blood and liver compared to ⁶⁴Cu-labeled analogs with less stable chelators (Figure below).

(A) MicroPET images (projection; two bed positions) obtained in AR42J tumor-bearing rats injected with either CB-TE2A-Y3-TATE (0.774 mCi, 3.5 μg) (left) or 64Cu-TETA-Y3-TATE (0.727 mCi, 2.7 μg) (right) at 4 h post-injection. (B) 64Cu activity uptake at 1, 4, and 24 h post-administration of 64Cu-CB-TE2A-Y3-TATE or 64Cu-TETA-Y3-TATE. Standard uptake values (SUV) for liver and kidneys. (C) SUV for tumor. SUVs were calculated by measuring the activity in ROIs from microPET images of AR42J pancreatic tumor-bearing Lewis rats (n = 2, mean ± SEM).

For the NHLBI-PEN project, we will evaluate more stable chelators as carriers of ⁶⁴Cu on the nanoparticle constructs. We will also evaluate ⁶⁴Cu-labeled α_Vβ₃ integrin ligands, both small molecule and nanoparticle analogs, in animal models of vascular injury.

The Division of Radiological Sciences has 14 research laboratories comprising 3,225 square feet. The laboratories are equipped for synthesis and evaluation of radioactive and non-radioactive compounds. Specific equipment includes a cell culture suite, normal/reversed-phase and size-exclusion HPLC systems, a LC-Mass Spectrometer, radio-TLC scanners, radioactivity dose calibrators, two autoradiography devices, gamma and beta counting equipment, uv-visible-fluorescent plate reader and a microbeta plate reader.

The imaging component of this grant is centered around the use of the Concorde (Knoxville, TN) microPET small animal imaging PET scanners. We currently have a microPET Focus 120 and a microPET Focus 220. These scanners have special resolution of 1.51 mm in the center of the field of view, with a sensitivity of 3.1%. We also have access to a microCT system (microCAT II, Imtek, Inc., Knoxville, TN). This scanner has resolution of 40-100 microns with rapid acquisition and reconstruction times. The microCT and microPET images have co-registration capabilities. A Bioscan Inc. NanoSPECT/CT imaging system was recently purchased by David Piwnica-Worms and the WU Molecular Imaging Center. In early 2006, this small animal imaging system will be available to the NHLBI-PEN for gamma imaging with radionuclides such as ¹¹¹In.