We proposed a novel PET protocol, which allows shortening of the total PET duration with sequential administration of two tracers. To calculate quantitative OEF, CBF and CMRO2 images, a mathematical formulation was developed. This formulation can be applied both in H215O–15O2 and 15O2–H215O, and enables estimating the quantitative functions from the PET scan by the residual radioactivity first administrated and built into a model. To test validity and applicability, accuracy and precision of quantitative values of OEF, CBF, and CMRO2 obtained by the present DARG, we compared them with the three-step ARG approach in our experimental study using monkeys. The accuracy of the functional values was confirmed and the enhancement of statistical noise was reasonably small. The global OEF values obtained by the present method also agreed well with those obtained by the arterial-sinus difference measurement. In addition, the simulation study showed that the error sensitivity of the present method was almost of the same degree as the three-step method. These findings suggest that the present protocol could be applicable to human studies.