Test-retest reliability and convergent validity of (R)-[¹¹C]PK11195 outcome measures without arterial input function

The PET radioligand (R)-[¹¹C]PK11195 is used to quantify the 18-kDa translocator protein (TSPO), a marker for glial activation. Since there is no brain region devoid of TSPO, an arterial input function (AIF) is ideally required for quantification of binding. However, obtaining an AIF is experimentally demanding, is sometimes uncomfortable for participants, and can introduce additional measurement error during quantification. The objective of this study was to perform an evaluation of the test-retest reliability and convergent validity of techniques used for quantifying (R)-[¹¹C]PK11195 binding without an AIF in clinical studies.

Data from six healthy individuals who participated in two PET examinations, 6 weeks apart, were analyzed. Regional non-displaceable binding potential (BP_ND) values were calculated using the simplified reference tissue model, with either cerebellum as reference region or a reference input derived using supervised cluster analysis (SVCA). Standardized uptake values (SUVs) were estimated for the time interval of 40-60 min.

Test-retest reliability for BP_ND estimates were poor (80% of ICCs < 0.5). BP_ND estimates derived without an AIF were not correlated with BP_ND, total or specific distribution volume from the 2TCM using an AIF (all R² < 12%). SUVs showed moderate reliability but no correlation to any other outcome measure.

Caution is warranted when interpreting patient-control comparisons employing (R)-[¹¹C]PK11195 outcome measures obtained without an AIF.