Summary Time-of-flight positron emission tomography is a very effective nuclear imaging modality for the diagnosis and staging of a range of pathologies such as cancer, cardiovascular diseases, or musculoskeletal disorders. Commercial TOF-PET scanners currently employ lutetium-(yttrium)-oxyorthosilicate (L(Y)SO) crystal detectors coupled to silicon photomultipliers (SiPMs) to achieve coincidence time resolutions (CTR) between 200-500 ps full width at half maximum (FWHM). High production costs of L(Y)SO crystals and their intrinsic radiation background are currently hindering the evolution and spread of very promising TOF-PET modalities such as long axial field-of-view (LA-FOV) scanners or studies involving very low doses such as cell tracking or imaging with theranostic agents. New scintillator materials with lower production cost, radiation background-free, and with TOF-level timing accuracy are needed. We propose to use thallium chloride (TlCl) as a scintillator material for TOF-PET. TlCl is a material with a simple cubic structure that allows for a relatively easy and flexible doping process. Preliminary data obtained with TlCl crystals doped with beryllium (Be) and indium (I) show a very fast scintillation component of ~10 ns that has a high potential for very accurate timing measurements. TlCl has a greater detection efficiency than LYSO or even bismuth germanate (BGO) for 511 keV gammas, is background radiation-free, and its estimated production cost is 1/3 of L(Y)SO based on its low melting point of 430C (compared to 2050C for L(Y)SO) and simple lattice structure. Moreover, unlike BGO, TlCl uniquely combines a very fast scintillation process with a high Cherenkov generation yield to further boost timing potential. We aim to prove the feasibility of using TlCl detectors for TOF-PET by combining expertise in crystal growth, simulation of light generation and detection, and benchtop characterization. First, will study the effects of Be and I as dopants in TlCl with the aim of further improve the scintillation properties observed in the preliminary data. We will also optimize the surface treatment of TlCl to maximize the light extraction toward the photodetector. Second, we will develop a simulation framework that allows us to guide the crystal development process and to understand the fundamental timing limits of TlCl. Third, we will characterize individual TlCl crystals with different choices of photodetectors to evaluate their timing and energy resolution accuracy. Results obtained with these crystals will be used to tune and validate the simulation model as well. Finally, we will evaluate the performance of TlCl detector blocks of 4x4 crystal elements. We will evaluate their timing resolution, depth-of-interaction estimation accuracy, and quality of flood histograms.