¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) is being used much more for response monitoring in multi-center studies. By visual assessment, positron emission tomography (PET) will be scored as negative or positive according to the abnormal ¹⁸F-fluorodeoxyglucose (FDG) uptake at previously involved sites. However, a gray-zone does exist especially in interim-PET scans. Besides visual inspection, semi-quantitative analyses using standardized uptake values (SUVs) allow for an objective assessment of treatment response, thereby eliminating observer variation and providing the opportunity to reduce the gray-zone by adding the quantitative power of PET. However, comparison of SUV results is often hampered by the wide variability in methodology of data acquisition, image reconstruction, and data analysis procedures. In the Netherlands, a protocol for standardization and quantification of FDG-PET whole body studies has been defined for the accurate use of SUVs in FDG-PET multi-center studies. Here, we report a summary of the main issues.