True molecular imaging is generated by compounds that target specific bio-molecules or molecular pathways. We propose to develop a solid-phase radiolabeling process that will lead to higher sensitivity radiopharmaceuticals with a higher margin of safety (nano-dosing) for molecular imaging and targeted radiotherapeutics. The approach should lead to rapid production of ultra-high specific activity radioiodine labeled radiopharmaceuticals with no other chemical components in the final solution except the injection vehicle. This process will help realize the era of true "carrier free" radiopharmaceutical preparations that will enhance target uptake and avoid potential pharmacological and toxic effects of excess active cold drug. Our previous efforts support the use of solid phase radiolabeling methods to achieve this nano-dosing concept. Our target molecule for solid-phase production is radiolabeled meta-iodobenzylguanidine (MIBG), a radiopharmaceutical used in children to detect and treat tumors originating from the neural crest and visualization of adrenergic tone of the heart. Two synthetic approaches will be used to obtain different variations of the solid-phase MIBG precursor. The first involves polymerization of custom organo-tincontaining divinylbenzene monomers to produce a rigid highly cross-linked resin. The second adds the organo-tin linker to preformed, porous, low cross-linked polymer beads. The different processes will produce solid-phase polymers with different 3-dimensional physical properties. Each will be evaluated for radiochemical and pharmaceutical performance with emphasis on radiolabeling methods and specific regulatory considerations as they pertain to eventual GMP manufacture. Choosing the most consistent and robust solid-phase resin with the optimal performance for radiolabeling is essential for ultimate FDA approval. The analytical profile of the products obtained will be compared to determine the safest and most efficient manufacturing process. Specifications for the polymer precursor must be established to produce arge scale GMP quality material for validation studies. The ultimate goal is to achieve a highly robust process for the production of radioiodinated Pharmaceuticals at ultra-high specific activity.