Authors: Catharina M L Zegers Wouter van Elmpt Katrin Szardenings Hartmuth Kolb Alan Waxman Rathan M Subramaniam Dae Hyuk Moon Jacqueline C Brunetti Shyam M Srinivas Philippe Lambin David Chien
Publish Date: 2015/07/02
Volume: 42, Issue: 12, Pages: 1840-1849
Abstract
Nine patients with lung cancer and ten with head and neck cancer were included in the analysis NCT01075399 Two sequential pretreatment 18FHX4 PET/CT scans were acquired within 1 week The maximal and mean standardized uptake values SUVmax and SUVmean were defined and the tumortobackground ratios TBR were calculated In addition hypoxic volumes were determined as the volume of the tumor with a TBR 12 HV12 Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated To evaluate the spatial repeatability of the uptake the PET/CT images were registered and a voxelwise comparison of the uptake was performed providing a correlation coefficientAll parameters of 18FHX4 uptake were significantly correlated between scans SUVmax r = 0958 p 0001 SUVmean r = 0946 p 0001 TBRmax r = 0962 p 0001 and HV12 r = 0995 p 0001 The relative coefficients of repeatability were 15 SUVmean 17 SUVmax and 17 TBRmax Voxelwise analysis of the spatial uptake pattern within the tumors provided an average correlation of 065 ± 014Repeated hypoxia PET scans with 18FHX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer 18FHX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxiatargeted treatments18FHX4 is a new 2nitroimidazole PET imaging agent for hypoxia in which structure–activity relationships have been used to optimize pharmacokinetic and clearance properties 1 2 Tumor hypoxia is a condition in which insufficiently vascularized tumor cells deprived of oxygen not only become more aggressive and malignant but also more resistant to treatment by radiation and chemotherapy 3 4 5 The presence of hypoxia is therefore generally considered a poor prognostic disease marker in cancer patients 6 However it is difficult to measure oxygen levels reproducibly and noninvasively in a highly heterogeneous tumor environment Reliable diagnostic methods to detect and quantify tumor hypoxia are therefore needed It has been hypothesized and currently being investigated that inclusion of hypoxic cell sensitizers during treatment ie the delivery of higher radiotherapy doses to hypoxic regions 7 or the use of hypoxiatargeting therapy 8 9 10 11 might improve the outcome in patients with hypoxic tumors 12 18FHX4 has the potential to serve as a clinically useful diagnostic tool to aid the use of hypoxiatargeting therapies in those patients who will most likely benefit from them 13 14This pilot phase 2 study was primarily designed as a test–retest study to investigate the repeatability of 18FHX4 as a noninvasive PET imaging marker for detection of tumor hypoxic regions Here we present the results in patients with lung cancer and patients with head and neck HN cancer
Keywords: