Fluorothymidine Positron Emission Tomography (FLT-PET) Repeatability and Response Evaluation in Advanced Pancreatic Cancer Patients Treated with Gemcitabine-Based Chemotherapy

Angela Lamarca, Prakash Manoharan, Peter Julyan, Mahbubunnabi Tamal, Madhu Rao, Andrew Cotterill, Ioannis Trigonis, Mairead Mcnamara, Richard Hubner, Zarni Win, Juan Valle, Azeem Saleem

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: This study aimed to evaluate the feasibility and repeatability of [18F]-fluorothymidine positron emission tomography (FLT-PET) and its utility as a proliferative imaging marker to evaluate response in patients with advanced pancreatic adenocarcinoma (PDAC) receiving gemcitabine-based chemotherapy. Methods: PDAC patients due to commence gemcitabine-based chemotherapy underwent FLT-PET over 60 minutes, before (baseline) and after 28 days of chemotherapy. Repeatability was assessed by a second FLT-PET scan within 7 days of baseline scan and before starting chemotherapy. Scans were assessed by two independent physician’s to determine inter-reporter concordance. FLT-PET uptake over 45-60 minutes was estimated as maximum and mean standardised uptake values (SUVmax and SUVmean). Exploratory analysis of tissue biomarkers was performed from archival tissue samples. Results: All 18 of the 21 patients consented who were imaged had primary tumour in-situ and 83% had metastases with 60% in liver. 17 patients received gemcitabine-based treatment. Thirty-five FLT-PET scans were acquired (89% evaluable) and 26 lesions delineated (17 primary tumours, 9 liver metastases). At baseline, liver metastases showed higher uptake compared with primary tumour with mean (SD) SUVmax [7.2 (1.1) vs 4.5 (1.3); p < 0.001] and SUVmean [4.7 (0.6) vs 2.1 (0.6); p < 0.001)]. There was good intra-patient repeatability and inter-reporter concordance with mean (SD) test-retest difference and inter-reporter Lin’s concordance coefficient being 4.9% (17.6) and 0.703 for SUVmax and -5.4% (SD 9.8) and 0.710 for SUVmean, respectively. FLT uptake between baseline and post-treatment scans were variable and did not predict for benefit from gemcitabine. However, gemcitabine-capecitabine combination therapy resulted in a higher FLT uptake compared to gemcitabine alone, although this did not translate to clinical benefit. No relationship was observed between tissue markers and FLT in half subjects imaged whose tissue was available. Conclusions FLT-PET is a feasible and reproducible imaging technique in patients with PDAC to evaluate proliferation-targeting therapy, using a simplified imaging protocol in well-designed clinical trials.
Original languageEnglish
JournalClinical Oncology and Research
Early online date27 Nov 2019
DOIs
Publication statusPublished - 2019

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

Fingerprint

Dive into the research topics of 'Fluorothymidine Positron Emission Tomography (FLT-PET) Repeatability and Response Evaluation in Advanced Pancreatic Cancer Patients Treated with Gemcitabine-Based Chemotherapy'. Together they form a unique fingerprint.

Cite this