Estimation of the binding potential BP_ND without a reference region or blood samples for brain PET studies

Binding potential (BP_ND) is a commonly used PET outcome measure because it can be estimated without blood sampling if a brain reference region (RR) devoid of the target of interest exists. For many radioligands, however, no RR exists, and the total distribution volume (V_T), whose estimation requires arterial blood sampling, is normally considered as the outcome measure. Here, we present a method that allows calculation of BP_ND without requiring either blood samples or a RR. The method extends our previous algorithm for estimating non-displaceable distribution volumes (V_ND) without using a RR. Here we show that if a template input function, with arbitrary amplitude but a shape similar to the actual arterial input function, is used in the algorithm, estimation of V_T and V_ND are both proportionally biased, and thus this bias cancels out in the estimation of BP_ND. The method is evaluated using simulated data, human data acquired with the serotonin 1A receptor radioligand [¹¹C]WAY-100635, and blocking data acquired in baboons using the serotonin 1A receptor radioligand [¹¹C]CUMI-101. We evaluated two versions of template input functions: an arbitrarily downscaled version of the actual arterial input function, and an unscaled population-based input function. In addition, we evaluated how shape modifications of the template input function impact the estimates of BP_ND. With the downscaled input function, BP_ND values close to the gold standard were obtained. When the unscaled population-based based input function was used, greater variability was observed but no discernable bias was introduced. When the input function shape was modified, a systematic but small bias in BP_ND was introduced. We conclude that, provided the shape of the arterial input function is adequately described, determination of its amplitude is not necessary for estimation of BP_ND.