Funds are requested for acquisition of a real time charged particle autoradiographic imager for the Johns Hopkins University. This device will assist molecular target detection (whole body and tissue distribution, target specificity), radioligand development (pharmacokinetics and pharmacological specificity, correlation with protein expression), radiopharmaceutical dosimetry (both whole body and tissue dosimetry). Investigations of protein regulation, cell proliferation, tissue metabolism and vascularization will also be enhanced. The Biospace Measures Beta Imager 2000Z charged particle imaging system (2000Z) has been selected because of its multiple advantages. Its large field of view will permit whole body autoradiography and its high sensitivity will permit imaging of H-3 labeled ligands. With the 2000Z positrons, betas, alphas and electrons associated with various radiotracers can be detected at spatial resolutions of 60 to 500 micrometer, at a detection threshold of 0.007 cpm/mm2 for 3H and with an efficiency as high as 90%. Linearity of the imager is within 2 % over the dynamic range of 104. The 2000Z Imager allows simultaneous detection of two or three isotopes using decay time differences or charged particle energies for discrimination. Multiple labeling opens up new applications with simultaneous quantification of several molecular targets at a time which will support drug and radioligand selectivity studies. Data are collected in list mode making it possible to retrospectively examine images acquired over different collection time-periods. The device can display the collected image in real-time, thereby eliminating under and over-exposures. RELEVANCE: The 2000Z Imager will be regularly employed by a major group of NIH funded researchers. Each of the included projects have strong NIH funding and are relevant to public health. They cover development of radiopharmaceuticals and radiation methodologies to treat cancer and diagnostic methods for improved detection of cancer and cardiovascular diseases. This instrument will have a strong impact on the development of new radioligands and for validation of new quantification algorithms for PET and SPECT. It will be also essential in the development of radionuclide therapies based on beta and alpha particle radiation and will significantly impact selection of ligands and isotopes, methods of delivery, estimation of dosimetry, and measurement of treatment response. [unreadable] [unreadable] [unreadable]