In vivo dual-tracer compartment model for cell-surface receptors. ROIT(t) and ROIU(t) represent the measured uptake curves of the targeted and untargeted tracers, respectively, in any region of interest, as a function of time, t; ηT and ηU are the imaging system detection efficiencies for the targeted and untargeted tracers (see text for details); K1 and k2 are the rates of exchange of the tracers from the blood concentration (Cp) to the interstitial space (Cf,2 for the targeted tracer and Cf,1 for the untargeted tracer) and back, respectively; and k3 and k4 are the rates of association and dissociation of the targeted tracer to its receptor in a bound state (Cb), respectively. The fraction plasma volume in the tissue is represented by vp. The red circled fraction in the black bordered equation is the parameter attained by the pixel-by-pixel or reference tissue normalization approaches explored in this study. The BP, underlined in red, is known as the “binding potential” and is the key parameter of interest: it is equivalent to k3/k4 and proportional to the receptor concentration by the tracer affinity.