Purpose: The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (F-FPPRGD) in cancer patients and to compare its uptake in malignant lesions with F-FDG uptake. Methods: A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had F-FPPRGD PET/CT prior to treatment. Maximum standardized uptake values (SUV) and mean SUV (SUV) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between F-FPPRGD uptake and F-FDG uptake were also evaluated in 28 of the 35 patients. Results: Areas of high F-FPPRGD accumulation (SUV range 8.9 - 94.4, SUV range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV range 2.1 - 6.3, SUV range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with F-FDG, F-FPPRGD showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV and SUV) for F FPPRGD and those for F-FDG. Conclusion: The biodistribution of F-FPPRGD in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between F-FPPRGD and F-FDG uptake confirms that the information provided by each PET tracer is different. [ABSTRACT FROM AUTHOR]