Metal Fluorination For biomolecules: Expanding The Radiofluorination Toolbox

Summary
Radiofluorination is one of the most important processes in molecular imaging, and to date, metal-
centered fluorination by either substitution or exchange mechanisms have been infrequently
designed and implemented for short-lived fluorine-18 since its inception in the early 1970s. The
broad aims of the project are to develop new methods of fluorine-18 incorporation into complex
molecules by using irreversible metal-fluorine bond formation. This will both complement and
contrast the currently existing fluorination methods for radiochemistry, including that of aluminium
fluoride (AlF), which has proven successful but with some apparent limitations. Each metal center
will be evaluated for its pharmacological properties, as well as indirect effects such as the capacity
to act as a multi-modality core or ability to pair with a therapeutic isotope in the same chelator to
create a theranostic pair, and upon testing the suitable functionality that the methods are resistant
to, we will demonstrate the best routes (as defined by the properties measured previously) in a
head-to-head against currently existing AlF radiolabeling for a well-known biological target,
prostate-specific membrane antigen (PSMA) and carbonic anhydrase IX (CAIX), that we have
extensive experience in handling and imaging in-house. At the same time, application of
successful methods within the GMP set-up will enable swift future translation and progress of a
method, rather than being abandoned as unsuitable for human-use.

Grant Number: 1R21EB035675-01A1
NIH Institute/Center: NIH
Principal Investigator: Laurence Carroll