Molecular Modeling in Metal Based Imaging Agent Design

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Metal based radio pharmaceuticals are widely used in diagnostic imaging and radiotherapy. Molecular modeling is an under utilized tool in understanding the in vivo behavior of radiometal complexes and designing new radiometal based imaging and the therapeutic agents. A major goal of this work will involve the development of new force fields for metals of interest in imaging modalities such as SPECT, PET and MRI, these include copper, gallium, indium, technetium, and gadolinium. A second goal is the development of computer based methods for predicting the octanol/water partition coefficient for metal chelate complexes. A third goal will be probing the relationship between the structural and electronic natures of metal- bifunctional chelate (BFC) complexes and the biological behavior of metal BFC-biomolecule conjugates. The development of such tools will significantly aid the development of new metal based imaging and potentially therapeutic agents. Molecular mechanics force fields for metals of interest will allow the prediction of stability, charge, and lipophilicity all of which significantly affects the in vivo behavior of the metal-ligand complex. At present the dearth of computer aided molecular design techniques which can handle metal chelate complexes hinders the rapid development of the new metal based imaging agents with their unique radiochemical or magnetic behaviors.