[18F]F-PEG-folate PET

[18F]F-PEG-folate ([18F]F-SFB-folate) is a folate analogue (Gent et al., 2013) that binds to folate receptor α and β (FRα and FRβ) with similar affinities, followed by internalization into cells. FRα is overexpressed in certain types of cancer, and FRβ is expressed on activated macrophages in sites of inflammation and in autoimmune diseases, including arthritis. [18F]F-PEG-folate has shown excellent results in assessment of arthritis and treatment response in animal studies (Chandrupatla et al., 2017, 2018a, 2018b), and very promising initial results in humans with rheumatoid arthritis (Verweij et al., 2020). Effective dose is lower than with [18F]FDG (Verweij et al., 2020).

The in vitro affinity of [18F]F-PEG-folate to folate receptors is 1.8-fold lower than that of folate, but 3-fold higher than that of 5-methyltetrahydrofolate (Gent et al., 2013), which is the primary biologically active form of folate. Binding to folate receptors in vivo is specific, as shown with rat arthritis model where the uptake of [18F]F-PEG-folate in arthritic sites was blocked by glucosamine-folate (Gent et al., 2013).

60-min PET scans have been performed in [18F]fluoro-PEG-folate in rats (Chandrupatla et al., 2018b) and in humans (Verweij et al., 2020). Radioactivity is rapidly cleared from blood, leading to plateau in arthritic joints already ∼ 1 min after tracer administration. In the arthritic joints the tissue radioactivity concentration was increasing very slowly until the end of the scan (60 min), while in healthy joints the concentration decreased rapidly (Verweij et al., 2020).

In human studies with arterial plasma sampling and metabolite analysis, irreversible two-tissue compartment model with vascular volume fraction was found to provide the best fitting to data (Verweij et al., 2020). Compartment model based Ki correlated linearly with SUV. Arterial sampling may not be necessary, since Kis estimated with venous sampling and arterial sampling correlated well (Verweij et al., 2020).

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Chandrupatla DMSH, Molthoff CFM, Lammertsma AA, van der Laken CJ, Jansen G. The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis. Drug Deliv Transl Res. 2019; 9(1): 366-378. doi: 10.1007/s13346-018-0589-2.

Paulos CM, Turk MJ, Breur GJ, Low PS. Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis. Adv Drug Deliv Rev. 2004; 56(8): 1205-1217. doi: 10.1016/j.addr.2004.01.012.

Steinz MM, Ezdoglian A, Khodadust F, Molthoff CFM, Srinivasarao M, Low PS, Zwezerijnen GJC, Yaqub M, Beaino W, Windhorst AD, Tas SW, Jansen G, van der Laken CJ. Folate receptor beta for macrophage imaging in rheumatoid arthritis. Front Immunol. 2022; 13: 819163. doi: 10.3389/fimmu.2022.819163.

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Updated at: 2023-02-27
Created at: 2023-02-26
Written by: Vesa Oikonen