Abstract
{sup 99m}Tc-technetium ({sup 99m}Tc) and {sup 188}Re-rhenium ({sup 188}Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first {sup 188}Re-folate derivative [{sup 188}Re(CO){sub 3}-picolylamine monoacetic acid 188Re-PAMA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural {sup 99m}Tc-analog [{sup 99m}Tc-PAMA folate (1)] reported previously. Methods: In vitro stability of compound was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. Results: Cell binding experiments showed high and FR-specific uptake. In vivo, compound accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) [: 1.87{+-}0.04 percent injected dose per gram of weight tissue (% ID/g) vs. : 2.33{+-}0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04{+-}0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity (: 14.5{+-}1.32, 4 h p.i.) was lower than for compound (58.0{+-}12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range (: 0.15{+-}0.01 vs. : 0.13{+-}0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed
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Mueller, Cristina;
[1]
Schubiger, P August;
[1]
Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)];
Schibli, Roger;
[1]
Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch
- Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland)
Citation Formats
Mueller, Cristina, Schubiger, P August, Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], Schibli, Roger, and Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch.
Isostructural folate conjugates radiolabeled with the matched pair {sup 99m}Tc/{sup 188}Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors.
United Kingdom: N. p.,
2007.
Web.
doi:10.1016/j.nucmedbio.2007.05.011.
Mueller, Cristina, Schubiger, P August, Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], Schibli, Roger, & Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch.
Isostructural folate conjugates radiolabeled with the matched pair {sup 99m}Tc/{sup 188}Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors.
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2007.05.011
Mueller, Cristina, Schubiger, P August, Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], Schibli, Roger, and Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch.
2007.
"Isostructural folate conjugates radiolabeled with the matched pair {sup 99m}Tc/{sup 188}Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors."
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2007.05.011.
@misc{etde_21026558,
title = {Isostructural folate conjugates radiolabeled with the matched pair {sup 99m}Tc/{sup 188}Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors}
author = {Mueller, Cristina, Schubiger, P August, Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], Schibli, Roger, and Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch}
abstractNote = {{sup 99m}Tc-technetium ({sup 99m}Tc) and {sup 188}Re-rhenium ({sup 188}Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first {sup 188}Re-folate derivative [{sup 188}Re(CO){sub 3}-picolylamine monoacetic acid 188Re-PAMA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural {sup 99m}Tc-analog [{sup 99m}Tc-PAMA folate (1)] reported previously. Methods: In vitro stability of compound was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. Results: Cell binding experiments showed high and FR-specific uptake. In vivo, compound accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) [: 1.87{+-}0.04 percent injected dose per gram of weight tissue (% ID/g) vs. : 2.33{+-}0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04{+-}0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity (: 14.5{+-}1.32, 4 h p.i.) was lower than for compound (58.0{+-}12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range (: 0.15{+-}0.01 vs. : 0.13{+-}0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed significantly improved the tumor-to-kidney ratio (: 1.59{+-}0.30, 4 h p.i.). Conclusions: The isostructural radiofolates and displayed almost identical pharmacokinetic profiles and accumulated both specifically in FR-positive tumors. However, only the coapplication of the antifolate pemetrexed improved the biodistribution of the radiotracers in such ways that a potential therapeutic application of compound can be envisaged in the future.}
doi = {10.1016/j.nucmedbio.2007.05.011}
journal = []
issue = {6}
volume = {34}
place = {United Kingdom}
year = {2007}
month = {Aug}
}
title = {Isostructural folate conjugates radiolabeled with the matched pair {sup 99m}Tc/{sup 188}Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors}
author = {Mueller, Cristina, Schubiger, P August, Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], Schibli, Roger, and Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)], E-mail: roger.schibli@pharma.ethz.ch}
abstractNote = {{sup 99m}Tc-technetium ({sup 99m}Tc) and {sup 188}Re-rhenium ({sup 188}Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first {sup 188}Re-folate derivative [{sup 188}Re(CO){sub 3}-picolylamine monoacetic acid 188Re-PAMA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural {sup 99m}Tc-analog [{sup 99m}Tc-PAMA folate (1)] reported previously. Methods: In vitro stability of compound was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. Results: Cell binding experiments showed high and FR-specific uptake. In vivo, compound accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) [: 1.87{+-}0.04 percent injected dose per gram of weight tissue (% ID/g) vs. : 2.33{+-}0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04{+-}0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity (: 14.5{+-}1.32, 4 h p.i.) was lower than for compound (58.0{+-}12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range (: 0.15{+-}0.01 vs. : 0.13{+-}0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed significantly improved the tumor-to-kidney ratio (: 1.59{+-}0.30, 4 h p.i.). Conclusions: The isostructural radiofolates and displayed almost identical pharmacokinetic profiles and accumulated both specifically in FR-positive tumors. However, only the coapplication of the antifolate pemetrexed improved the biodistribution of the radiotracers in such ways that a potential therapeutic application of compound can be envisaged in the future.}
doi = {10.1016/j.nucmedbio.2007.05.011}
journal = []
issue = {6}
volume = {34}
place = {United Kingdom}
year = {2007}
month = {Aug}
}