The performance of positron emission tomography (PET) scanners is dictated, to a large extent, by the properties and dimensions of the scintillator elements used to form the detectors. Critical properties of the scintillator material include its brightness, its stopping power and its decay time. Because of its fundamental importance in nuclear medicine imaging, and the limitations of current scintillator materials, research into new detector materials remains active. In this proposal, we study the potential for a rare-earth garnet, (GdxLu1-x)3(GayAl1-y)5O12:Ce (abbreviated as GLuGAG) to be used as a scintillator in PET detectors. It has an unprecedented combination of properties, including high stopping power (attenuation length 1.3 cm at 511 keV), high light yield (~66,000 photons/MeV deposited) and a fast decay time (~40 ns), and unlike most other very bright scintillators, it is not moisture sensitive. Because it has a cubic crystal structure, it also can be fabricated using ceramic techniques. This allows the material to be made at lower temperatures and more quickly than conventional scintillators grown as single crystals. It also offers tantalizing possibilities for directly fabricating scintillator elements in the desired size and shape with no cutting. Ceramic scintillators therefore have the potential to result in much lower cost materials compared with traditional scintillators. Several years of development and characterization work on GLuGAG has been completed and at this stage small samples of materials with excellent properties can be reliably fabricated using ceramic techniques. The goals of this proposal are to i) fine-tune the composition of GLuGAG to minimize the decay time and maximize the light output; ii) to fully characterize the scintillation properties of GLuGAG; iii) to scale up the volume of material produced such that it is large enough for a complete PET block detector unit; iv) to investigate directly fabricating elements in the size and shape required; v) to characterize the performance of GLuGAG elements of appropriate sizes for PET applications in terms of energy resolution and timing resolution; vi) and to build and evaluate pairs of complete PET detector modules for comparison against the performance of existing commercial detectors in terms of spatial resolution, efficiency, energy and timing resolution. We also will explore more advanced PET detector designs with dual-ended readout for depth- encoding, and read out of GLuGAG scintillator arrays using large-area silicon photomultiplier technology. The combination of GLuGAG's outstanding scintillation properties, and the ability to fabricate it with high transparency using ceramic approaches (a feature not shared by any other scintillator with plausible density for PET applications) offers tremendous potential to favorably and significantly shift the cost/performance trade-off in PET detector design, thereby impacting all applications of PET from the clinic through small-animal research.