The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in (18)F-deoxyglucose (FDG) or (18)F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy.A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting.Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV(ave)), to assess reproducibility, showed only a small difference in physiological uptake (-0.006 ± 0.224 in 118 follow-up FDG scans and 0.09 ± 0.81 in 111 follow-up FLT scans).It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol.