Simultaneous dual-isotope positron emission tomography (PET) is used to improve disease evaluation. Two distinct molecular probes are simultaneously provided to the imaging target. One of the probes is labeled with a radionuclide that emits positrons to provide double coincidence events in PET. The other probe is labeled with a radionuclide that emits positrons+prompt gammas to provide triple coincidence events in PET. One of the probes is a metabolic probe, and the other probe is a selective probe that includes a ligand or antibody that is biologically responsive to receptor/antigen status. A PET system is employed that can provide simultaneous double coincidence and triple coincidence PET images. The resulting images provide simultaneous metabolic imaging and receptor/antigen imaging. Applications include disease evaluation, such as cancer staging (e.g., for breast cancer, prostate cancer, etc.).