Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice.
BACKGROUND: 3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-prolife...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2945761?pdf=render |
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| author | Mette Munk Jensen Kamille Dumong Erichsen Fredrik Björkling Jacob Madsen Peter Buhl Jensen Liselotte Højgaard Maxwell Sehested Andreas Kjær |
| author_facet | Mette Munk Jensen Kamille Dumong Erichsen Fredrik Björkling Jacob Madsen Peter Buhl Jensen Liselotte Højgaard Maxwell Sehested Andreas Kjær |
| author_sort | Mette Munk Jensen |
| collection | DOAJ |
| description | BACKGROUND: 3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET. METHODOLOGY/PRINCIPAL FINDINGS: In vivo uptake of (18)F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline (18)F-FLT scans were made before either Top216 (n = 7-10) or vehicle (n = 5-7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2'-deoxy-2'-[(18)F]fluoro-D-glucose ((18)F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). (18)F-FLT uptake decreased significantly at 2 hours (-52%; P<0.001), 6 hours (-49%; P = 0.002) and Day 1 (-47%; P<0.001) after Top216 treatment. At Day 5 (18)F-FLT uptake was comparable to uptake in the control group. Uptake of (18)F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of (18)F-FDG was significantly decreased at 6 hours (-21%; P = 0.003), Day 1 (-29%; P<0.001) and Day 5 (-19%; P = 0.05) compared to baseline. CONCLUSIONS/SIGNIFICANCE: One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by (18)F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that (18)F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients. |
| first_indexed | 2024-12-13T04:26:51Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:26:51Z |
| publishDate | 2010-01-01 |
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| spelling | doaj.art-f837851f6efe488b8236523fb82142082022-12-21T23:59:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0159e1296510.1371/journal.pone.0012965Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice.Mette Munk JensenKamille Dumong ErichsenFredrik BjörklingJacob MadsenPeter Buhl JensenLiselotte HøjgaardMaxwell SehestedAndreas KjærBACKGROUND: 3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET. METHODOLOGY/PRINCIPAL FINDINGS: In vivo uptake of (18)F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline (18)F-FLT scans were made before either Top216 (n = 7-10) or vehicle (n = 5-7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2'-deoxy-2'-[(18)F]fluoro-D-glucose ((18)F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). (18)F-FLT uptake decreased significantly at 2 hours (-52%; P<0.001), 6 hours (-49%; P = 0.002) and Day 1 (-47%; P<0.001) after Top216 treatment. At Day 5 (18)F-FLT uptake was comparable to uptake in the control group. Uptake of (18)F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of (18)F-FDG was significantly decreased at 6 hours (-21%; P = 0.003), Day 1 (-29%; P<0.001) and Day 5 (-19%; P = 0.05) compared to baseline. CONCLUSIONS/SIGNIFICANCE: One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by (18)F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that (18)F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.http://europepmc.org/articles/PMC2945761?pdf=render |
| spellingShingle | Mette Munk Jensen Kamille Dumong Erichsen Fredrik Björkling Jacob Madsen Peter Buhl Jensen Liselotte Højgaard Maxwell Sehested Andreas Kjær Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. PLoS ONE |
| title | Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. |
| title_full | Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. |
| title_fullStr | Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. |
| title_full_unstemmed | Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. |
| title_short | Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. |
| title_sort | early detection of response to experimental chemotherapeutic top216 with 18f flt and 18f fdg pet in human ovary cancer xenografts in mice |
| url | http://europepmc.org/articles/PMC2945761?pdf=render |
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