A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography
Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[<sup>18</sup>F]fluorothymidine positron emission tomography (<sup>18</sup>F-FLT P...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/14/3718 |
| _version_ | 1797589888089980928 |
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| author | Preetha Aravind Sanjay Popat Tara D. Barwick Neil Soneji Mark Lythgoe Katherina B. Sreter Jingky P. Lozano-Kuehne Mattias Bergqvist Neva Patel Eric O. Aboagye Laura M. Kenny |
| author_facet | Preetha Aravind Sanjay Popat Tara D. Barwick Neil Soneji Mark Lythgoe Katherina B. Sreter Jingky P. Lozano-Kuehne Mattias Bergqvist Neva Patel Eric O. Aboagye Laura M. Kenny |
| author_sort | Preetha Aravind |
| collection | DOAJ |
| description | Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[<sup>18</sup>F]fluorothymidine positron emission tomography (<sup>18</sup>F-FLT PET). We determined the magnitude of the <sup>18</sup>F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent <sup>18</sup>F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The <sup>18</sup>F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed <sup>18</sup>F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An <sup>18</sup>F-FLT flare occurred in all lesions in 1 patient, while another patient had an <sup>18</sup>F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (<i>p</i> < 0.001) and <sup>18</sup>F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (<i>p</i> = 0.004 each). Notably, 83% (5/6) of patients who exhibited <sup>18</sup>F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit <sup>18</sup>F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an <sup>18</sup>F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC. |
| first_indexed | 2024-03-11T01:12:31Z |
| format | Article |
| id | doaj.art-4d800044274c415189f5740614cef4f4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T01:12:31Z |
| publishDate | 2023-07-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4d800044274c415189f5740614cef4f42023-11-18T18:43:09ZengMDPI AGCancers2072-66942023-07-011514371810.3390/cancers15143718A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission TomographyPreetha Aravind0Sanjay Popat1Tara D. Barwick2Neil Soneji3Mark Lythgoe4Katherina B. Sreter5Jingky P. Lozano-Kuehne6Mattias Bergqvist7Neva Patel8Eric O. Aboagye9Laura M. Kenny10Department of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKLung Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKLung Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKBiovica International, Uppsala Science Park, 75237 Uppsala, SwedenDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKDepartment of Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UKThymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory “flare” in 3′-deoxy-3′-[<sup>18</sup>F]fluorothymidine positron emission tomography (<sup>18</sup>F-FLT PET). We determined the magnitude of the <sup>18</sup>F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent <sup>18</sup>F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The <sup>18</sup>F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed <sup>18</sup>F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An <sup>18</sup>F-FLT flare occurred in all lesions in 1 patient, while another patient had an <sup>18</sup>F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (<i>p</i> < 0.001) and <sup>18</sup>F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (<i>p</i> = 0.004 each). Notably, 83% (5/6) of patients who exhibited <sup>18</sup>F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit <sup>18</sup>F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an <sup>18</sup>F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC.https://www.mdpi.com/2072-6694/15/14/3718NSCLC<sup>18</sup>F-FLTPETpemetrexedthymidine kinase |
| spellingShingle | Preetha Aravind Sanjay Popat Tara D. Barwick Neil Soneji Mark Lythgoe Katherina B. Sreter Jingky P. Lozano-Kuehne Mattias Bergqvist Neva Patel Eric O. Aboagye Laura M. Kenny A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography Cancers NSCLC <sup>18</sup>F-FLT PET pemetrexed thymidine kinase |
| title | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography |
| title_full | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography |
| title_fullStr | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography |
| title_full_unstemmed | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography |
| title_short | A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show <sup>18</sup>F-Fluorothymidine “Flare” on Positron Emission Tomography |
| title_sort | subset of non small cell lung cancer patients treated with pemetrexed show sup 18 sup f fluorothymidine flare on positron emission tomography |
| topic | NSCLC <sup>18</sup>F-FLT PET pemetrexed thymidine kinase |
| url | https://www.mdpi.com/2072-6694/15/14/3718 |
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