A stable total imaging signal can conceal changes in one component of binding.
The human PET experiment used zolpidem to investigate subtype contributions to radiolabeled Ro15-4513 and flumazenil binding. Total Ro15-4513 distribution volume did not decrease clearly, while spectral analysis identified a component reduced by zolpidem and another relatively unaffected component, interpreted in relation to receptor subtypes.
The subtype interpretation depended on tracer selectivity and kinetic modeling rather than direct counting of each receptor. Brain regions required different model treatment. Distribution volume, receptor occupancy and clinical sedation are related but distinct quantities.
An expert should specify whether a conclusion comes from a total signal or a modeled component. A negative total-signal result cannot automatically exclude a subtype effect. Conversely, a modeled occupancy finding does not independently establish an individual’s memory, alertness or driving ability at another time.
Source: PMC3318150, supplied full-text paper. Findings are paraphrased; forensic implications are an interpretation.
Related: Flumazenil PET in Fragile X Syndrome Measures Binding Availability.