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To measure the variability of cardiac uptake on serial whole-body 18F-FDG PET scans.Two hundred and eighteen whole-body PET scans were performed in 47 patients with different primary malignancies between October 1996 and April 2003 on a dedicated PET system. The number of scans per patient ranged between four and nine. Two experienced nuclear medicine physicians reviewed the scans retrospectively using the non-attenuation corrected images to assess the cardiac FDG uptake. Patients with cardiac uptake less or equal to lung uptake were assigned in the ‘low’ uptake group, and those with cardiac uptake more than the lung uptake were assigned to the ‘high’ uptake group. The reproducibility of cardiac uptake on serial whole-body PET scans and the effect of age, sex, weight, diabetes and primary diagnosis on cardiac uptake was evaluated.There was very good reproducibility (intra-class correlation coefficient=0.77) of individual cardiac FDG uptake on serial whole-body PET scans. Diabetics (n=6) in comparison to non-diabetics were less likely to have high cardiac uptake (odds ratio (OR)=0.24, P<0.05). Patients with lymphoma (n=12) in comparison to patients with other primary diagnoses were more likely to have high cardiac uptake (OR=8.6, P<0.05). There was no association between cardiac uptake and age, sex or weight.Cardiac FDG uptake on whole-body PET does not appear to change significantly over time. It is likely that uptake is determined by individual characteristics; these likely include diabetes and primary diagnosis of lymphoma.