Comparative Analysis of Folate Derived PET Imaging
Agents with [<sup>18</sup>F]-2-Fluoro-2-deoxy‑d‑glucose
Using a Rodent Inflammatory Paw Model
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Abstract
Activated
macrophages play a significant role in initiation and
progression of inflammatory diseases and may serve as the basis for
the development of targeted diagnostic methods for imaging sites of
inflammation. Folate receptor beta (FR-β) is differentially
expressed on activated macrophages associated with inflammatory disease
states yet is absent in either quiescent or resting macrophages. Because
folate binds with high affinity to FR-β, development of folate
directed imaging agents has proceeded rapidly in the past decade.
However, reports of PET based imaging agents for use in inflammatory
conditions remain limited. To investigate whether FR-β expressing
macrophages could be exploited for PET based inflammatory imaging,
two separate folate-targeted PET imaging agents were developed, 4-[<sup>18</sup>F]-fluorophenylfolate and [<sup>68</sup>Ga]-DOTA-folate,
and their ability to target activated macrophages were examined in
a rodent inflammatory paw model. We further compared inflamed tissue
uptake with 2-[<sup>18</sup>F]fluoro-2-deoxy-d-glucose ([<sup>18</sup>F]-FDG). microPET analysis demonstrated that both folate-targeted
PET tracers had higher uptake in the inflamed paw compared to the
control paw. When these radiotracers were compared to [<sup>18</sup>F]-FDG, both folate PET tracers had a higher signal-to-noise ratio
(SNR) than [<sup>18</sup>F]-FDG, suggesting that folate tracers may
be superior to [<sup>18</sup>F]-FDG in detecting diseases with an
inflammatory component. Moreover, both folate-PET imaging agents also
bind to FR-α which is overexpressed on multiple human cancers.
Therefore, these folate derived PET tracers may also find use for
localizing and staging FR<sup>+</sup> cancers, monitoring response
to therapy, and for selecting patients for tandem folate-targeted
therapies