Automated synthesis ofN-(2-[18F]Fluoropropionyl)-<scp>l</scp>-glutamic acid as an amino acid tracer for tumor imaging on a modified [18F]FDG synthesis module

Liu, Shaoyu; Sun, Aixia; Zhang, Zhanwen; Tang, Xiaolan; Nie, Dan; Ma, Hui; Jiang, Shende; Tang, Ganghua

doi:10.1002/jlcr.3505

Cited by 3 publications

(3 citation statements)

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“…and N-(2-[ 18 F]fluoropropionyl)-L-glutamic acid [10][11][12][13]. (S)-4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) is an L-glutamate derivative used with PET for tumour detection and visualisation through targeting of the cystine/glutamate antiporter protein (xCTor SLC7A11), which is a subunit of the transport system x c − [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Soloviev

Lewis

2022

Mol Imaging Biol

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Purpose (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is an L-glutamate derivative used as a PET biomarker to assess intracellular redox status in vivo through targeting of the cystine/glutamate antiporter protein, xc− transporter. In this report, we describe a radiosynthesis of [18F]FSPG for use in PET studies that address specific challenges in relation to the radiotracer purity, molar activity, and quality control testing methods. Procedures The radiosynthesis of [18F]FSPG was performed using a customised RNPlus Research automated radiosynthesis system (Synthra GmbH, Hamburg, Germany). [18F]FSPG was labelled in the 3-fluoropropylmoiety at the 4-position of the glutamic acid backbone with fluorine-18 via substitution of nucleophilic [18F]fluoride with a protected naphthylsulfonyloxy-propyl-L-glutamate derivative. Radiochemical purity of the final product was determined by radio HPLC using a new method of direct analysis using a Hypercarb C18 column. Results The average radioactivity yield of [18F]FSPG was 4.2 GBq (range, 3.4–4.8 GBq) at the end of synthesis, starting from 16 GBq of [18F]fluoride at the end of bombardment (n = 10) in a synthesis time of 50 min. The average molar activity and radioactivity volumetric concentration at the end of synthesis were 66 GBq µmol−1 (range, 48–73 GBq µmol−1) and 343–400 MBq mL−1, respectively. Conclusion Stability tests using a 4.6 GBq dose with a radioactivity volumetric concentration of 369 MBq mL−1 at the end of synthesis showed no observable radiolysis 3 h after production. The formulated product is of high radiochemical purity (> 95%) and higher molar activity compared to previous methods and is safe to inject into mice up to 3 h after production.

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Section: Introductionmentioning

confidence: 99%

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Soloviev

Lewis

2022

Mol Imaging Biol

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“…[ 18 F]FPGLU (Liu et al, 2017;Sun et al, 2017), (2S,4R)-4-fluorol-glutamate ([ 18 F](2S,4R)4F-GLU) (Ploessl et al, 2012), and 3.…”

Section: Discussionmentioning

confidence: 99%

Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma

Lei

Xiang

et al. 2021

Front. Chem.

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Purpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-labeled glutamate analog, [18F]AlF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl)-l-glutamate ([18F]AlF-NOTA-NSC-GLU), for HCC imaging.Procedures: [18F]AlF-NOTA-NSC-GLU was synthesized via a one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AlF-NOTA-NSC-GLU in HCC, we conducted positron emission tomography/computed tomography (PET/CT) imaging and competitive binding of [18F]AlF-NOTA-NSC-GLU in human Hep3B tumor-bearing mice. The transport mechanism of [18F]AlF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro.Results: [18F]AlF-NOTA-NSC-GLU was prepared with an overall radiochemical yield of 29.3 ± 5.6% (n = 10) without decay correction within 20 min. In vitro competitive inhibition experiments demonstrated that the Na+-dependent systems XAG-, B0+, ASC, and minor XC- were involved in the uptake of [18F]AlF-NOTA-NSC-GLU, with the Na+-dependent system XAG- possibly playing a more dominant role. Protein incorporation studies of the Hep3B human hepatoma cell line showed almost no protein incorporation. Micro-PET/CT imaging with [18F]AlF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B human hepatoma-bearing mouse models. After [18F]AlF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AlF-NOTA-NSC-GLU was 2.06 ± 0.17 at 30 min post-injection. In vivo competitive binding experiments showed that the tumor-to-liver uptake ratio decreased with the addition of inhibitors to block the XAG system.Conclusions: We have successfully synthesized [18F]AlF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AlF-NOTA-NSC-GLU may be a potential candidate for HCC imaging. Also, a further biological evaluation is underway.

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“…Tab. 2 The comparisons of [ 18 F]AIF-NOTA-NSC-GLU, [ 18 F]FPGLU*, [ 18 F]FSPG* and [ 18 F](2S,4R)4F-GLU* *Data were first published by[37][38][39]41]…”

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confidence: 99%

Biological evaluation of [18F]AIF-NOTA-NSC-GLU as a PET tracer for hepatocellular carcinoma

Lin

Xiang

et al. 2020

Preprint

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Purpose 18F-labeled amino acids (AAs) as tumor-specific imaging agents play a critical role in hepatocellular carcinoma (HCC) imaging. In this work, we evaluated the synthesis and biological properties of a simple 18F-labeled glutamate analogue, [18F]AIF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl))-l-glutamate ([18F]AIF-NOTA-NSC-GLU) for HCC imaging via one-step reaction sequence. Methods [18F]AIF-NOTA-NSC-GLU was synthesized via the one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AIF-NOTA-NSC-GLU in HCC, we conducted PET/CT imaging and competitive binding of [18F]AIF-NOTA-NSC-GLU in human Hep3B 2.1-7 tumor-bearing mice. The transport mechanism of [18F]AIF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro. Results [18F]AIF-NOTA-NSC-GLU was prepared with decay-corrected radiochemical yield of 29.3 ± 5.6% (n=10) within 20 min. In vitro competitive inhibition experiments demonstrated that Na+-dependent Systems XAG-, B0+, ASC and minor XC- were involved in the uptake of [18F]AIF-NOTA-NSC-GLU, with Na+-dependent System XAG- possibly playing a more dominant role. Protein incorporation studies of the Hep3B 2.1-7 human hepatoma cell line found almost no protein incorporation. Micro-PET/CT imaging with [18F]AIF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B 2.1-7 human hepatoma-bearing mouse models. After [18F]AIF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AIF-NOTA-NSC-GLU reached the peak at 30 min post-injection (2.06 ± 0.17). In vivo competitive binding experiments exhibited that the tumor-to-liver uptake ratio decreased by the addition of the inhibitors to block the system XAG-. Conclusion We have successfully synthesized [18F]AIF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AIF-NOTA-NSC-GLU might have good clinical potential as a PET tumor-detecting agent for HCC imaging.

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Automated synthesis ofN-(2-[¹⁸F]Fluoropropionyl)-l-glutamic acid as an amino acid tracer for tumor imaging on a modified [¹⁸F]FDG synthesis module

Cited by 3 publications

References 15 publications

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma

Biological evaluation of [18F]AIF-NOTA-NSC-GLU as a PET tracer for hepatocellular carcinoma

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Automated synthesis ofN-(2-[18F]Fluoropropionyl)-l-glutamic acid as an amino acid tracer for tumor imaging on a modified [18F]FDG synthesis module

Cited by 3 publications

References 15 publications

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid

Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma

Biological evaluation of [18F]AIF-NOTA-NSC-GLU as a PET tracer for hepatocellular carcinoma

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Automated synthesis ofN-(2-[¹⁸F]Fluoropropionyl)-l-glutamic acid as an amino acid tracer for tumor imaging on a modified [¹⁸F]FDG synthesis module