ArticlePloS one2013
Pemetrexed induced thymidylate synthase inhibition in non-small cell lung cancer patients: a pilot study with 3'-deoxy-3'-[¹⁸F]fluorothymidine positron emission tomography.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Role of 3'-Deoxy-3'-[JTO clinical and research reports · 2022Article
- STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Clinical value of 3'-deoxy-3'-[Insights into imaging · 2021Review
- Liver background uptake of [American journal of nuclear medicine and molecular imaging · 2020Article
- Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases.Journal of experimental & clinical cancer research : CR · 2019Article
- Using Radiolabeled 3'-Deoxy-3'-Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018Article
- Article
- Early detection of thymidylate synthase resistance in non-small cell lung cancer with FLT-PET imaging.Oncotarget · 2017Article
- Response Monitoring with [Molecular imaging and biology · 2017Article
- Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small cell lung cancer with FLT-PET imaging.Oncotarget · 2017Article
- Applications of PET imaging with the proliferation marker [18F]-FLT.The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... · 2015Review
- Metabolically active tumour volume segmentation from dynamic [(18)F]FLT PET studies in non-small cell lung cancer.EJNMMI research · 2015Article
- Rapamycin downregulates thymidylate synthase and potentiates the activity of pemetrexed in non-small cell lung cancer.Oncotarget · 2014Article
- CNS metastases in breast cancer: old challenge, new frontiers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesPemetrexed is a thymidylate synthase (TS) inhibitor and is effective in non-small cell lung cancer (NSCLC). 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT), a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients.
methodsFourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET) scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST), time to progression (TTP) and overall survival (OS) were determined.
resultsEleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months); median OS was 13.0 months (range 5.1-30.8 months). Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS.
conclusionsMeasuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in ¹⁸F-FLT uptake within the tumor. No significant association with tumor response, TTP or OS was observed.
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