Abstract LED Radiofluidics is developing an apparatus that allows direct or easy conversion of small molecule drug candidates to positron emission tomography (PET) agents via radiofluorination with a readily accessible, and inexpensive LED light source. PET is a powerful, rapidly developing technology that plays key roles in medical imaging, as well as drug discovery and development. Despite the exceptional promise, the availability of novel PET agents is limited due to the lack of efficient and simple labeling methods to modify biologically active small molecules/drugs. Many small molecule pharmaceuticals and therapeutics contain aromatic or heteroaromatic systems within their framework; thus, it would be highly desirable for radiolabels to be introduced to this common organic subunit easily and efficiently. Unfortunately, current methods to radiofluorinate inactivated arene compounds have only limited success, and often requires complicated synthesis to access the desired precursors and/or special O2-free handling techniques. Progress has been made however, with photoredox systems developed by the Nicewicz and Li groups at the University of North Carolina at Chapel Hill; their work describes arene C–H fluorination with 18F – that allows direct conversion of drugs to PET agents. They also have determined that the nucleophilic aromatic substitution (SNAr) and halogen exchange reactions can precisely control the radiofluorination position on aromatic substrates when conducting radiofluorination of C-OR2 or C-X (X = F, Cl, Br, I, NO2) bonds. While these approaches offer simple, efficient late stage radiofluorination, both methods require an expensive laser light source, and it is anticipated that the setup could be difficult to automate. However, LED Radiofluidics’ innovative and affordable device, using an inexpensive light source (~$200) can offer an answer for the unmet need for diverse PET agents via our photoredox-based development of radiofluorinated PET agents. The goal of this application is to establish feasibility of the envisioned radiofluorination device as a first step toward making this paradigm shifting technology readily available to the field. The specific aims of this Phase I project are: 1: To develop a prototype device based on flow reaction and microfluidics using an LED as the light source, with the goal of greatly reducing the cost of the light reactor without compromising radiolabeling yields. An initial module supporting synthesis of an [18F]F-DOPA derivative will be co-developed with the device, such that this well-established photoredox radiolabeling reaction can be demonstrated and optimized on the device, and 2: To demonstrate the ability of the concept by fluorinating members of a class of existing small molecule pharmaceuticals. Informed by the initial design established in Aim 1, the three synthetic methods identified will be developed and tested in the device built in Aim 1. LED Radiofluidics hypothesize the microfl...