To compare prospectively the accuracy of positron emission tomography (PET) with leukocytes labeled in vitro with (18)F fluorodeoxyglucose (FDG) versus that of conventional scintigraphy with leukocytes labeled in vitro with (111)In oxine in patients suspected of having infection. This HIPAA-compliant study had institutional review board approval; informed consent was obtained from all patients. Patients were 25 men and 26 women aged 32-86 years. In vitro labeling of autologous human leukocytes with FDG and (111)In-oxine was performed according to published methods. Labeling efficiencies and cell viability were determined. Imaging was performed 2.5-5.8 hours after injection of 196-315 MBq of FDG-labeled leukocytes and approximately 24 hours after injection of 17-25 MBq of (111)In-oxine-labeled leukocytes. Forty-three (20 men, 23 women; mean age, 59 years; range, 32-86 years) patients could be successfully imaged with both tracers. Six patients were not injected with FDG-labeled leukocytes because of low labeling efficiency (<35%). Two patients were injected with FDG-labeled leukocytes but were not imaged. One reader interpreted all results as positive or negative for infection. Imaging results were compared with final diagnoses. Labeling efficiencies and cell viabilities were compared by using the paired t test. Differences between PET and scintigraphy were determined by using the McNemar test. For the 43 patients who were imaged with both tracers, labeling efficiency of FDG was lower than that of (111)In oxine (72% +/- 8 [standard deviation] vs 90% +/- 5, P < .001). Viability of FDG-labeled leukocytes was not different from that of (111)In-oxine-labeled leukocytes (98% +/- 1 vs 97% +/- 3). There were no differences between FDG PET and (111)In scintigraphy in terms of sensitivity (87% vs 73%), specificity (82% vs 86%), or accuracy (84% vs 81%). PET with FDG-labeled leukocytes was comparable to scintigraphy with (111)In-oxine-labeled leukocytes. Further investigation in a larger population with dedicated PET or PET/computed tomography seems warranted. Copyright RSNA, 2006.