Optimal sampling schedule (OSS) is of great interest in biomedical experiment design, as it can improve the physiological parameter estimation precision and significantly reduce the samples required. A number of well designed algorithms and software packages have been developed, which deal with the instantaneous measurements at discrete times. However, in nuclear medicine tracer kinetic studies, the imaging systems, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), take measurements (images) based on continuous accumulation over time intervals. In this case, the existing algorithms cannot be used to design OSS so as to reduce the image frame numbers. In this paper, a general OSS design algorithm for the accumulative measurement is proposed. The potential usefulness of the algorithm is demonstrated by its designing OSS in [18F] fluoro-2-deoxy-D-glucose (FDG) studies with PET to estimate the local cerebral metabolic rate of glucose. The robustness of parameter estimation using the OSS with respect to intra-subject and inter-subject parameter variations is also presented.