F-18 labelled 3’-deoxy-3’-fluorothymidine (FLT) positron emission tomography (PET) imaging in patients with advanced pancreatic ductal adenocarcinoma: proof-of-concept reproducibility sub-analysis.


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Angela Lamarca1,Prakash Manoharan2,Marie-Claude Asselin3,Peter J Julyan4,Mahbubunnabi Tamal3,Ioannis Trigonis3,Mairéad G McNamara5,Richard A Hubner1,Zarni Win6,Juan W Valle5,Azeem Saleem7
1Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom,2Department of Radiology, The Christie NHS Foundation Trust, Manchester, United Kingdom,3University of Manchester Wolfson Molecular Imaging Centre (WMIC), Institute of Population Health, Manchester, United Kingdom,4Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, United Kingdom,5Department of Medical Oncology, The Christie NHS Foundation Trust; Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom,6Department of Radiology, Imperial College Healthcare NHS Trust, London, United Kingdom,7Department of Applications, Imanova Centre for Imaging Sciences, London, United Kingdom

Abstract

Background

The thymidine analogue FLT is transported and phosphorylated in proliferating cells. FLT tumour uptake correlates with proliferation.

Method

Advanced pancreatic ductal adenocarcinoma (PDAC) patients with target lesion >2cm due to start chemotherapy were eligible. Dynamic FLT PET/CT scanning was performed over 60min, before starting chemotherapy (baseline scan, BS). Intra-patient reproducibility was explored by a second FLT scan within 7 days of BS and before chemotherapy (reproducibility scan, RPS). Lesions were manually delineated by two independent radiologists for determination of inter-radiologist concordance. FLT uptake in the primary tumour and metastases was quantified as standardised uptake value (SUV, mean and max) over 45-60min.

Results

Of the 21 patients consented 18 were scanned, all with primary tumour in situ and 83% with distant metastases (60% in liver). Thirty-five FLT scans were acquired for the whole study, 21 scans were analysed for this reproducibility sub-analysis (17 BS, 4 RPS) and 27 lesions delineated. At baseline, median SUVmean and SUVmax were 1.9 (95%CI 1.8-2.1) and 5.9 (95%CI 4.6-7.8), respectively, for the primary (n=17) and 4.6 (95%CI 3.7-5.2) and 8.9 (95%CI 8.2-10.5), respectively, for metastatic lesions (n=10; 9 liver, 1 lymph node). Intra-patient reproducibility between BS and RPS was good (all lesions; n=8): mean change and standard deviation (SD) of test-retest differences and Lin’s concordance coefficient (LCC) for SUVmean (mean change -5.4%; SD 9.8%; LCC 0.947, p<0.001) were superior to SUVmax (mean change 7.9%; SD 19.2%; LCC 0.642, p<0.001). The reproducibility achieved by the second radiologist was similar (6 lesions): SUVmean (mean change -10.3%, SD 12.8%; LCC 0.534, p=0.005) and SUVmax (mean change 4.7%, SD 14.5%; LCC 0.826, p<0.001). Inter-radiologist concordance was assessed by comparing 12 lesions (8 scans; 4 BS, 4 RPS): LCC for SUVmean and SUVmax were 0.635 (p<0.001) and 0.489 (p=0.019), respectively.

Conclusion

FLT-PET is feasible and reproducible (intra-patient and inter-radiologist) in patients with advanced PDAC.