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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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1H-NMR of cold fluoropropoxytryptophan (FTP).
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fig3: 1H-NMR of cold fluoropropoxytryptophan (FTP).

Mentions: After hydrolysis, 1H NMR of fluoropropoxytryptophan (FTP) is shown in Figure 3. During radiosynthesis, the activity of N-Boc-18F-fluoropropoxytryptophan methyl ester was 0.30 GBq (55.63%, decay-corrected). The radioactivity, radiochemical yield, and end-of-synthesis (EOS) time for 18F-FTP were 0.13 GBq, 37.73% (decay-corrected), and 90 min, respectively. Radio-TLC (1 M ammonium acetate : methanol = 4 : 1, v/v) showed that the retarded factor (Rf) value was 0.9. HPLC of tosyl precursor and 18F-FTP showed that the retention time (Rt) was 16 min and 9 min, respectively (Figure 4(a)). The no-carrier-added displacement product corresponded to the unlabeled FTP under the same TLC and HPLC system. Radiochemical purity determined by HPLC and radio-TLC of the title compound was >96% (Figure 4). The specific activity of 18F-FTP determined by HPLC was 74 GBq/μmol. The pyrogenicity test (Bacterial Endotoxins) was <175 EU/4 mL and the pH was about 6.5. The product was sterile. There was no corruption for membrane filter integrity. LC-MS showed no more than 0.04% acetonitrile or methylene chloride of residual solvents in 18F-FTP product. Automated module for production of FTP and the flow chart of the module are shown in Figure 5.


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 cold fluoropropoxytryptophan (FTP).
© Copyright Policy
Related In: Results  -  Collection

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

fig3: 1H-NMR of cold fluoropropoxytryptophan (FTP).
Mentions: After hydrolysis, 1H NMR of fluoropropoxytryptophan (FTP) is shown in Figure 3. During radiosynthesis, the activity of N-Boc-18F-fluoropropoxytryptophan methyl ester was 0.30 GBq (55.63%, decay-corrected). The radioactivity, radiochemical yield, and end-of-synthesis (EOS) time for 18F-FTP were 0.13 GBq, 37.73% (decay-corrected), and 90 min, respectively. Radio-TLC (1 M ammonium acetate : methanol = 4 : 1, v/v) showed that the retarded factor (Rf) value was 0.9. HPLC of tosyl precursor and 18F-FTP showed that the retention time (Rt) was 16 min and 9 min, respectively (Figure 4(a)). The no-carrier-added displacement product corresponded to the unlabeled FTP under the same TLC and HPLC system. Radiochemical purity determined by HPLC and radio-TLC of the title compound was >96% (Figure 4). The specific activity of 18F-FTP determined by HPLC was 74 GBq/μmol. The pyrogenicity test (Bacterial Endotoxins) was <175 EU/4 mL and the pH was about 6.5. The product was sterile. There was no corruption for membrane filter integrity. LC-MS showed no more than 0.04% acetonitrile or methylene chloride of residual solvents in 18F-FTP product. Automated module for production of FTP and the flow chart of the module are shown in Figure 5.

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