Contribution to a conference proceedings/Journal Article

FZJ-2026-03767

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png (S)-7-[18F]F-FT-2102: A Candidate for mIDH1-PET Imaging

Gemki, M. (Corresponding author)FZJ* ; Schneider, D.FZJ* ; Schulze, A.FZJ* ; Bier, D.FZJ* ; Zlatopolskiy, B.FZJ* ; Neumaier, B.FZJ*

2025
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.nucmedbio.2025.109308

Abstract: Introduction: Somatic point mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification. However, current methods for detecting mutated IDH1 (mIDH1) require invasive tissue sampling, making them unsuitable for follow-up examinations or long-term studies. Positron emission tomography (PET) with mIDH1-selective radioligands is a promising approach to enable non-invasive assessment of the IDH status. Therefore, the aim of this study was to prepare and evaluate (S)-7-[18F]F-FT-2102, a radiofluorinated derivative of the FDA-approved mIDH1-selective inhibitor olutasidenib (FT-2102).[1] Methods: The Me3Sn-substituted radiolabeling precursor 1 and (S)-7-F-FT-2102 were prepared starting from a commercially available anthranilic acid derivative. The radiosynthesis of (S)-7-[18F]F-FT-2102 ([18F]2) (Scheme 1A) was performed by Cu-mediated radiofluorination with a NextGen Cu-mediator and the reaction conditions were optimized by a "Design of Experiments (DoE)" approach.[2] Cellular uptake of (S)-7-[18F]F-FT-2102 was investigatedin mIDH1-positive (U87-mIDH1) and -negative (U87-WT) glioma cells. Results: The precursor for radiolabeling and the reference compound were obtained in total yields of 14% and 15% over 14 and 9 steps, respectively. Subsequent radiofluorination under optimized reaction conditions (8.75 μmol precursor, 33.5 μmol [Cu(4-PhPy)4](ClO4)2 as mediator in 800 μL DMI at 115 °C for 10 minutes) followed by deprotection of the radiolabeled intermediate and HPLC purification afforded (S)-7-[18F]F-FT-2102 in radiochemical yields of 39 ± 10% (n = 9) over two steps (synthesis time: 130 ± 5 min; activity yield: 13 ± 4%), radiochemical purities of >99%, and molar activities of 43.0 – 84.2 GBq/μmol (Scheme 1A). Cellular uptake studies (Scheme 1B) demonstrated significantly higher accumulation of the tracer in U87-mIDH1 (5.2 ± 0.9%×100 μg protein-1) compared to U87-WT (2.6 ± 0.3%×100 μg protein-1) cells (p < 0.001). Conclusions: (S)-7-[18F]F-FT-2102 was successfully prepared in good radiochemical yields, molar activities, and purities using DOE-optimized NextGen Cu-mediated radiofluorination. Preferential accumulation of the tracer candidate in mIDH1-positive glioma cells justifies further preclinical evaluation of (S)-7-[18F]F-FT-2102 in suitable in vivo tumor models.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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