PROJECT SUMMARY / ABSTRACT Positron-emission tomography (PET) studies play a critical role in many areas of neurological health by enabling quantitative in vivo measurements of specific neuroreceptor systems (e.g. receptor density, drug occupancy, endogenous ligand occupancy) to (i) evaluate fundamental hypotheses about disease or (ii) aid in the development of novel treatments targeting those receptors. As biological understanding evolves, novel PET radiotracers targeting relevant receptors are continually being developed, but access to these novel PET ligands is extremely limited. Short half-lives limit tracer distribution beyond the initial institution where it was developed, and it can be very difficult for other investigators in the field to perform additional studies to evaluate, validate, or make use of the novel ligand. Due to the relatively infrequent usage in early stages, and the absence of foreseeable widespread diagnostic use for many neurotracers, commercial radiopharmacies are not interested in manufacturing them. Instead, researchers can only benefit from these novel tracers by producing the tracers themselves, an endeavor that incurs an enormous resource cost to set up suitable space and equipment, and then develop and optimize an in-house synthesis protocol for routine production. New microscale technologies for radiotracer production have the potential to overcome these challenges by reducing consumption of expensive reagents (~100x), increasing yields, and shortening synthesis times, and their compact size allows self-shielded operation and avoids the need for the infrastructure (hot cells) of a conventional radiochemistry lab. DropletPharm, Inc. is commercializing a droplet-based reaction technology in which radiotracers are prepared in high-yield and molar activity in a device the size of a coffee cup. By reducing costs of all aspects of tracer production (isotope, reagents, operator time, space, capital), and relying on commercial [18F]fluoride sources, this technology will enable a highly economical pathway to build out a “network” of low-cost radiopharmacies for supplying a variety of investigational PET tracers for researchers in academia and pharmaceutical companies. As a proof-of-concept, DropletPharm plans to adapt the radiosynthesis of an early-stage kappa opioid receptor (KOR) ligand, [18F]LY2459989, to the droplet radiosynthesizer, establish a cGMP compatible radiosynthesis process, and compare the costs (between conventional and droplet-based approaches) of the synthesis development effort as well as routine batch production. This particular ligand shows considerable promise for imaging the KOR / dynorphin systems in humans, and supplying it to researchers will benefit studies of a wide range of neuropsychiatric disorders in which KOR/dynorphin is implicated, including chronic pain, anxiety, depressive disorders, substance abuse and other conditions with far-reaching negative impacts on society. Success of the pro...