Pilot, proof-of-concept studies for determining the feasibility of the use of FLT-PET in patients with pancreatic adenocarcinoma.

Abstract

TPS4146 Background: Pancreatic cancer (PC) has one of the lowest 5-year survival rates. Gemcitabine (G)-based chemotherapy is standard-of-care first-line systemic therapy. Fluorine-18 radiolabelled 3-deoxy-3-fluorothymidine (FLT), a thymidine analogue, is a substrate for thymidine kinase 1 (TK1), which is highly expressed in proliferating cells in late G1/S phase. FLT uptake (imaged and quantified by positron emission tomography (PET)) correlates with pathology-based proliferation markers and with decreases with therapy in a number of cancers. G, a nucleoside analogue, decreases proliferation by inhibiting DNA synthesis, primarily acting on S and G1/S phase thus decreasing tumour FLT uptake. Human equilibrative nucleoside transporter (hENT1) transports G and FLT into cells, making hENT1 activity a key determinant of both FLT uptake and G efficacy. Methods: Two parallel proof-of-concept studies are designed to explore the feasibility of assessing proliferation, nucleoside transport, magnitude of treatment-related FLT uptake changes and understanding the pathophysiological basis of FLT-PET imaging in patients (pts) with (1) localized or (2) advanced PC. Up to 24 PC pts with ECOG PS 0-2, able to undergo imaging and with at least one potentially evaluable lesion larger than 2cm on CT/MRI are eligible. Pts with localized disease (study 1) will have dynamic FLT-PET pre-operatively preceded by a radiolabelled H2O PET scan to assess tumour perfusion. These pts will also undergo 2-deoxy-2-fluoro-D-glucose (FDG)-PET and diffusion-weighted MR scans. For pts with metastatic disease (study 2), dynamic FLT-PET will be performed before and after G-based chemotherapy. FLT uptake expressed as a standardized uptake value (SUV), will be determined. Tumour pathological markers from the surgical samples and imaging parameters will be correlated; hENT1 status will be assessed (by immunohistochemistry) after surgery (study 1) and before treatment (study 2). Reproducibility FLT-PET studies will be performed in a cohort of subjects to assess the variability in uptake quantification.