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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

1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester (a) and N-Boc-fluoropropoxytryptophan methyl ester (b).
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fig2: 1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester (a) and N-Boc-fluoropropoxytryptophan methyl ester (b).

Mentions: Using N-Boc-tosylpropoxytryptophan methyl ester as a precursor, we are able to shorten the synthetic step to one-step synthesis. 1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester and N-Boc-fluoropropoxytryptophan methyl ester are shown in Figure 2.


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)

1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester (a) and N-Boc-fluoropropoxytryptophan methyl ester (b).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: 1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester (a) and N-Boc-fluoropropoxytryptophan methyl ester (b).
Mentions: Using N-Boc-tosylpropoxytryptophan methyl ester as a precursor, we are able to shorten the synthetic step to one-step synthesis. 1H-NMR of N-Boc-tosylpropoxytryptophan methyl ester and N-Boc-fluoropropoxytryptophan methyl ester are shown in Figure 2.

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