[18F]AlF-NOTA-folate PET

[18F]AlF-NOTA-folate conjugate (Chen et al., 2016) binds specifically to folate receptors, which facilitate the transport of folate and folate conjugates in to the cells. In contrast, the reduced folate carrier and Proton-coupled folate transporter cannot transport conjugated folates. In preclinical studies, [18F]AlF-NOTA-folate accumulates in folate receptor positive tumours (Chen et al., 2016), macrophages in atherosclerotic plaques (Silvola et al., 2018), experimental autoimmune encephalomyelitis (EAE) lesions (Elo et al., 2019), autoimmune myocarditis (Jahandideh et al., 2020), murine model of acute colitis (Gerami et al., 2026), and gliomas (Miner et al., 2023).

Analysis methods

Model input function

Conversion of image-derived BTAC to PTAC

Folate receptors have been found on human erythrocytes and neutrophils (Høier-Madsen et al., 2008).

Plasma-to-blood ratio in mice is ∼1.5 (Chen et al., 2016; Silvola et al., 2018), and it stays relatively constant during the study (unpublished results), suggesting that a fraction of [18F]AlF-NOTA-folate is bound to blood cells. In rats, the plasma-to-blood ratio was closer to 2 (Jahandideh et al., 2020), suggesting that the tracer stays in plasma.

Metabolite correction

In rats, the fraction of intact [18F]AlF-NOTA-folate remains high during the PET scan: 0.88 at 60 min after administration (Elo et al., 2019).

Brain

Rat brain data with metabolite-corrected plasma input function can be analysed with Logan plot, providing regional distribution volume (DV) of the tracer (Elo et al., 2019), suggesting reversible [18F]AlF-NOTA-folate uptake in the brain. In the EAE model, contralateral hemisphere could be used as reference region, omitting the need for blood curve, either in Logan plot or SUVR (Elo et al., 2019).

Myocardium

In rat myocardial PET, both Logan and Patlak plots fit the data reasonably well, and both correlate with SUV (Jahandideh et al., 2020). This suggests that [18F]AlF-NOTA-folate uptake may have both reversible and irreversible components.


See also:


Literature

Chen Q, Meng X, McQuade P, Rubins D, Lin SA, Zeng Z, Haley H, Miller P, González Trotter D, Low PS. Synthesis and preclinical evaluation of folate-NOTA-Al18F for PET imaging of folate-receptor-positive tumors. Mol Pharm. 2016; 13(5): 1520-1527. doi: 10.1021/acs.molpharmaceut.5b00989.

Elo P, Li XG, Liljenbäck H, Helin S, Teuho J, Koskensalo K, Saunavaara V, Marjamäki P, Oikonen V, Virta J, Chen Q, Low PS, Knuuti J, Jalkanen S, Airas L, Roivainen A. Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats. J Neuroinflammation 2019; 16:252. doi: 10.1186/s12974-019-1612-3.

Jahandideh A, Uotila S, Ståhle M, Virta J, Li XG, Kytö V, Marjamäki P, Liljenbäck H, Taimen P, Oikonen V, Lehtonen J, Mäyränpää MI, Chen Q, Low PS, Knuuti J, Roivainen A, Saraste A. Folate receptor β-targeted PET imaging of macrophages in autoimmune myocarditis. J Nucl Med. 2020; 61(11): 1643-1649. doi: 10.2967/jnumed.119.241356.

Miner MWG, Liljenbäck H, Virta J, Kärnä S, Viitanen R, Elo P, Gardberg M, Teuho J, Saipa P, Rajander J, Mansour HMA, Cleveland NA, Low PS, Li XG, Roivainen A. High folate receptor expression in gliomas can be detected in vivo using folate-based positron emission tomography with high tumor-to-brain uptake ratio divulging potential future targeting possibilities. Front Immunol. 2023; 14:1145473. doi: 10.3389/fimmu.2023.1145473.

Silvola JMU, Li XG, Virta J, Marjamäki P, Liljenbäck H, Hytönen JP, Tarkia M, Saunavaara V, Hurme S, Palani S, Hakovirta H, Ylä-Herttuala S, Saukko P, Chen Q, Low PS, Knuuti J, Saraste A, Roivainen A. Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography. Sci Rep. 2018; 8(1):9720. doi: 10.1038/s41598-018-27618-4.



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Updated at: 2026-01-25
Created at: 2026-01-22
Written by: Vesa Oikonen