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Radiosynthesis, in vitro and preliminary biological evaluation of [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino) butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer

Tristan Baguet, Jakob Bouton, Jonas Janssens, Glenn Pauwelyn, Jeroen Verhoeven (UGent) , Benedicte Descamps (UGent) , Serge Van Calenbergh (UGent) , Christian Vanhove (UGent) and Filip De Vos (UGent)
(2020) JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 63(10). p.442-455
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Abstract
The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [H-3]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic mu PET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 +/- 1.90%. in vitro experiments show inhibitor constantsK(i)of 90 and 125 mu M for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth
Keywords
Organic Chemistry, Analytical Chemistry, Spectroscopy, Biochemistry, Drug Discovery, Radiology Nuclear Medicine and imaging, [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, [F-18]FABABA, glutamine, oncology, positron emission tomography, EXPRESSION, ASCT2

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MLA
Baguet, Tristan, et al. “Radiosynthesis, in Vitro and Preliminary Biological Evaluation of [F-18]2-Amino-4-((2-((3-Fluorobenzyl)Oxy)Benzyl)(2-((3-(Fluoromethyl)Benzyl)Oxy)Benzyl)Amino) Butanoic Acid, a Novel Alanine Serine Cysteine Transporter 2 Inhibitor-Based Positron Emission Tomography Tracer.” JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, vol. 63, no. 10, 2020, pp. 442–55, doi:10.1002/jlcr.3863.
APA
Baguet, T., Bouton, J., Janssens, J., Pauwelyn, G., Verhoeven, J., Descamps, B., … De Vos, F. (2020). Radiosynthesis, in vitro and preliminary biological evaluation of [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino) butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 63(10), 442–455. https://doi.org/10.1002/jlcr.3863
Chicago author-date
Baguet, Tristan, Jakob Bouton, Jonas Janssens, Glenn Pauwelyn, Jeroen Verhoeven, Benedicte Descamps, Serge Van Calenbergh, Christian Vanhove, and Filip De Vos. 2020. “Radiosynthesis, in Vitro and Preliminary Biological Evaluation of [F-18]2-Amino-4-((2-((3-Fluorobenzyl)Oxy)Benzyl)(2-((3-(Fluoromethyl)Benzyl)Oxy)Benzyl)Amino) Butanoic Acid, a Novel Alanine Serine Cysteine Transporter 2 Inhibitor-Based Positron Emission Tomography Tracer.” JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS 63 (10): 442–55. https://doi.org/10.1002/jlcr.3863.
Chicago author-date (all authors)
Baguet, Tristan, Jakob Bouton, Jonas Janssens, Glenn Pauwelyn, Jeroen Verhoeven, Benedicte Descamps, Serge Van Calenbergh, Christian Vanhove, and Filip De Vos. 2020. “Radiosynthesis, in Vitro and Preliminary Biological Evaluation of [F-18]2-Amino-4-((2-((3-Fluorobenzyl)Oxy)Benzyl)(2-((3-(Fluoromethyl)Benzyl)Oxy)Benzyl)Amino) Butanoic Acid, a Novel Alanine Serine Cysteine Transporter 2 Inhibitor-Based Positron Emission Tomography Tracer.” JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS 63 (10): 442–455. doi:10.1002/jlcr.3863.
Vancouver
1.
Baguet T, Bouton J, Janssens J, Pauwelyn G, Verhoeven J, Descamps B, et al. Radiosynthesis, in vitro and preliminary biological evaluation of [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino) butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 2020;63(10):442–55.
IEEE
[1]
T. Baguet et al., “Radiosynthesis, in vitro and preliminary biological evaluation of [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino) butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer,” JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, vol. 63, no. 10, pp. 442–455, 2020.
@article{8667070,
  abstract     = {{The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value. Hence, the aim of this study is to develop a fluorine-18-labeled version of a V-9302 analogue, one of the most potent inhibitors of ASCT-2. The precursor was labeled with fluorine-18 via a nucleophilic substitution of the corresponding benzylic bromide. The cold reference product was subjected to in vitro assays with [H-3]glutamine in a PC-3 and F98 cell line to determine the affinity for both the human and rat ASCT-2. To evaluate the tracer potential dynamic mu PET, images were acquired in a mouse xenograft model for prostate cancer. The tracer could be synthesized with an overall nondecay corrected yield of 3.66 +/- 1.90%. in vitro experiments show inhibitor constantsK(i)of 90 and 125 mu M for the PC-3 and F98 cells, respectively. The experiments in the PC-3 xenograft demonstrate a low uptake in the tumor tissue. We have successfully synthesized the radiotracer [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid. in vitro experiments show a good affinity for both the human and rat ASCT-2. However, the tracer suffers from poor in vivo tumor uptake in the PC-3 model. Briefly, we present the first fluorine-18-labeled derivative of compound V-9302, a promising novel ASCT-2 blocker used for inhibition of tumor growth}},
  author       = {{Baguet, Tristan and Bouton, Jakob and Janssens, Jonas and Pauwelyn, Glenn and Verhoeven, Jeroen and Descamps, Benedicte and Van Calenbergh, Serge and Vanhove, Christian and De Vos, Filip}},
  issn         = {{0362-4803}},
  journal      = {{JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS}},
  keywords     = {{Organic Chemistry,Analytical Chemistry,Spectroscopy,Biochemistry,Drug Discovery,Radiology Nuclear Medicine and imaging,[F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid,[F-18]FABABA,glutamine,oncology,positron emission tomography,EXPRESSION,ASCT2}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{442--455}},
  title        = {{Radiosynthesis, in vitro and preliminary biological evaluation of [F-18]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino) butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer}},
  url          = {{http://doi.org/10.1002/jlcr.3863}},
  volume       = {{63}},
  year         = {{2020}},
}
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