Development of LED Photoredox Radiolabeling Device

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 microfluidic device will
greatly increase the surface area exposed to the light source, leading to increased yields compared to traditional
set-ups.