LED Radiofluidics is developing an apparatus that allows direct or easy conversion of small molecule drugcandidates to positron emission tomography (PET) agents via radiofluorination with a readily accessible, andinexpensive LED light source. PET is a powerful, rapidly developing technology that plays key roles in medicalimaging, as well as drug discovery and development. Despite the exceptional promise, the availability of novelPET agents is limited due to the lack of efficient and simple labeling methods to modify biologically active smallmolecules/drugs. Many small molecule pharmaceuticals and therapeutics contain aromatic or heteroaromaticsystems within their framework; thus, it would be highly desirable for radiolabels to be introduced to this commonorganic subunit easily and efficiently.Unfortunately, current methods to radiofluorinate inactivated arene compounds have only limited success, andoften requires complicated synthesis to access the desired precursors and/or special O2-free handlingtechniques. Progress has been made however, with photoredox systems developed by the Nicewicz and Ligroups 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 aromaticsubstitution (SNAr) and halogen exchange reactions can precisely control the radiofluorination position onaromatic substrates when conducting radiofluorination of C-OR2 or C-X (X = F, Cl, Br, I, NO2) bonds. While theseapproaches offer simple, efficient late stage radiofluorination, both methods require an expensive laser lightsource, and it is anticipated that the setup could be difficult to automate. However, LED Radiofluidics' innovativeand affordable device, using an inexpensive light source (~$200) can offer an answer for the unmet need fordiverse 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 steptoward making this paradigm shifting technology readily available to the field. The specific aims of this Phase Iproject are: 1: To develop a prototype device based on flow reaction and microfluidics using an LED as the lightsource, 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, suchthat 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 moleculepharmaceuticals. Informed by the initial design established in Aim 1, the three synthetic methods identified willbe developed and tested in the device built in Aim 1. LED Radiofluidics hypothesize the microfluidic device willgreatly increase the surface area exposed to the light source, leading to increased yields compared to traditionalset-ups.
Public Health Relevance Statement: Narrative
LED Radiofluidics' photoredox radiolabeling device will add to the American economy and economic
competitiveness in the imaging arena, by offering competition to current imaging devices and their manufacturers
that cannot provide the diversity, ease of radiotracer synthesis and price of LED Radiofluidics' product.
Additionally, the device not only aids in advancing the health and wellness of Americans by producing a novel
selection of targeted PET agents that can improve the detection and diagnosis of disease, but there is potential
to help medical providers monitor treatment, and researchers to better understand biological and chemical
processes. Finally, LED Radiofluidics will be supporting and enhancing partnerships between academic
institutions, through connections between the University of North Carolina, and industry by creating partnerships
with various hospitals, biotech and pharmaceutical companies.
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