Limits...
18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L-PGDS enzyme.

Huang HL, Huang YC, Lee WY, Yeh CN, Lin KJ, Yu CS - PLoS ONE (2014)

Bottom Line: The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 ± 4.8% and 97.6 ± 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the isoform, microsomal prostaglandin E synthase 1.No binding to GST-alpha and GST-pi was observed.The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu, Taiwan.

ABSTRACT
Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9:1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP-HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 ± 4.8% and 97.6 ± 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST-pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS.

Show MeSH

Related in: MedlinePlus

Bar diagram for the radiometabolite analysis of the radiotracer using semipreparative RP-HPLC.The blood samples were taken at various time points after [18F]FBuEA-GS 3 was injected intravenously.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4128654&req=5

pone-0104118-g008: Bar diagram for the radiometabolite analysis of the radiotracer using semipreparative RP-HPLC.The blood samples were taken at various time points after [18F]FBuEA-GS 3 was injected intravenously.

Mentions: The radiometabolite of [18F]FBuEA-GS 3 was analyzed by semipreparative RP-HPLC (Fig. S6). Blood samples were taken from each rat at various times post injection. The subsequent HPLC chromatogram of the sample showed an identifiable peak corresponding to [18F]FBuEA-GS 3. The peaks of [18F]FBuEA-GS 3 in all chromatograms obtained from various time points were integrated and the radioactivity counts were plotted against time points (Fig. 8). The in vivo haliflife (t1/2) of [18F]FBuEA-GS 3 was determined to be 60 min.


18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L-PGDS enzyme.

Huang HL, Huang YC, Lee WY, Yeh CN, Lin KJ, Yu CS - PLoS ONE (2014)

Bar diagram for the radiometabolite analysis of the radiotracer using semipreparative RP-HPLC.The blood samples were taken at various time points after [18F]FBuEA-GS 3 was injected intravenously.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128654&req=5

pone-0104118-g008: Bar diagram for the radiometabolite analysis of the radiotracer using semipreparative RP-HPLC.The blood samples were taken at various time points after [18F]FBuEA-GS 3 was injected intravenously.
Mentions: The radiometabolite of [18F]FBuEA-GS 3 was analyzed by semipreparative RP-HPLC (Fig. S6). Blood samples were taken from each rat at various times post injection. The subsequent HPLC chromatogram of the sample showed an identifiable peak corresponding to [18F]FBuEA-GS 3. The peaks of [18F]FBuEA-GS 3 in all chromatograms obtained from various time points were integrated and the radioactivity counts were plotted against time points (Fig. 8). The in vivo haliflife (t1/2) of [18F]FBuEA-GS 3 was determined to be 60 min.

Bottom Line: The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 ± 4.8% and 97.6 ± 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the isoform, microsomal prostaglandin E synthase 1.No binding to GST-alpha and GST-pi was observed.The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu, Taiwan.

ABSTRACT
Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9:1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP-HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 ± 4.8% and 97.6 ± 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST-pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS.

Show MeSH
Related in: MedlinePlus