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Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging.

Shih IH, Duan XD, Kong FL, Williams MD, Yang K, Zhang YH, Yang DJ - Biomed Res Int (2014)

Bottom Line: Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time.However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model. (18)F-FTP could be synthesized with high radiochemical yield.Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Systems Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT

Objective: This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer.

Methods: Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv).

Results: Radio-TLC and HPLC analyses of (18)F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F-FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model.

Conclusion: (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

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Related in: MedlinePlus

Synthetic scheme of [18/19F]fluoropropoxytryptophan (18/19F-FTP).
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fig1: Synthetic scheme of [18/19F]fluoropropoxytryptophan (18/19F-FTP).

Mentions: The synthetic scheme of FTP is shown in Figure 1. Three steps were involved in the synthesis. In step 1, thionyl chloride (2.4 mL, 34 mmol) was dissolved in anhydrous methanol (100 mL) and cooled to 0°C. 5-Hydroxytryptophan (5.00 g, 22.7 mmol) was added in portions. After temperature returned to room temperature, the mixture was refluxed overnight. The solvent was evaporated, followed by silica-gel packed column chromatographic purification using ethyl acetate : hexane (4 : 1, v/v) as an eluent to yield 5-hydroxytryptophan methyl ester hydrochloride 5.18 g (84% yield). 1H-NMR (300 MHz, CDCl3): 7.23 (d, J = 8.7 Hz, 1 H), 7.15 (s, 1 H), 6.91 (d, J = 2.1 Hz, 1 H), 6.73 (dxd, J = 8.7, J′ = 2.3 Hz, 1 H), 4.29 (t, J = 6.3, 1 H), 3.83 (s, 3 H), and 3.26–3.42 (m, 2 H). 13C-NMR (300 MHz, CDCl3): 169.8, 150.8, 132.2, 127.9, 125.4, 112.2, 112.1, 105.6, 102.1, 53.5, 52.7, and 26.7.


Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging.

Shih IH, Duan XD, Kong FL, Williams MD, Yang K, Zhang YH, Yang DJ - Biomed Res Int (2014)

Synthetic scheme of [18/19F]fluoropropoxytryptophan (18/19F-FTP).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127279&req=5

fig1: Synthetic scheme of [18/19F]fluoropropoxytryptophan (18/19F-FTP).
Mentions: The synthetic scheme of FTP is shown in Figure 1. Three steps were involved in the synthesis. In step 1, thionyl chloride (2.4 mL, 34 mmol) was dissolved in anhydrous methanol (100 mL) and cooled to 0°C. 5-Hydroxytryptophan (5.00 g, 22.7 mmol) was added in portions. After temperature returned to room temperature, the mixture was refluxed overnight. The solvent was evaporated, followed by silica-gel packed column chromatographic purification using ethyl acetate : hexane (4 : 1, v/v) as an eluent to yield 5-hydroxytryptophan methyl ester hydrochloride 5.18 g (84% yield). 1H-NMR (300 MHz, CDCl3): 7.23 (d, J = 8.7 Hz, 1 H), 7.15 (s, 1 H), 6.91 (d, J = 2.1 Hz, 1 H), 6.73 (dxd, J = 8.7, J′ = 2.3 Hz, 1 H), 4.29 (t, J = 6.3, 1 H), 3.83 (s, 3 H), and 3.26–3.42 (m, 2 H). 13C-NMR (300 MHz, CDCl3): 169.8, 150.8, 132.2, 127.9, 125.4, 112.2, 112.1, 105.6, 102.1, 53.5, 52.7, and 26.7.

Bottom Line: Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time.However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model. (18)F-FTP could be synthesized with high radiochemical yield.Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Systems Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT

Objective: This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer.

Methods: Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv).

Results: Radio-TLC and HPLC analyses of (18)F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F-FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model.

Conclusion: (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

Show MeSH
Related in: MedlinePlus