A subset of non-small cell lung cancer patients treated with pemetrexed show 18f-fluorothymidine ‘flare’ on positron emission tomography

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Title: A subset of non-small cell lung cancer patients treated with pemetrexed show 18f-fluorothymidine ‘flare’ on positron emission tomography
Authors: Aboagye, E
Aravind, P
Popat, S
Barwick, TD
Soneji, N
Lythgoe, M
Sreter, KB
Lozano- Kuehne, JP
Bergqvist, M
Patel, N
Kenny, LM
Item Type: Journal Article
Abstract: 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′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-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 18F-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 18F-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 18F-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 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-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 18F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC.
Issue Date: 22-Jul-2023
Date of Acceptance: 20-Jul-2023
DOI: 10.3390/cancers15143718
ISSN: 2072-6694
Publisher: MDPI AG
Start Page: 1
End Page: 14
Journal / Book Title: Cancers
Volume: 15
Issue: 14
Copyright Statement: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Publication Status: Published
Article Number: 3718
Online Publication Date: 2023-07-22
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine

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