Feasibility study of TSPO quantification with 18FFEPPA using population-based input functionReport as inadecuate

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The input function IF is a core element in the quantification of Translocator protein 18 kDa with positron emission tomography PET, as no suitable reference region with negligible binding has been identified. Arterial blood sampling is indeed needed to create the IF ASIF. In the present manuscript we study individualization of a population based input function PBIF with a single arterial manual sample to estimate total distribution volume VT for 18FFEPPA and to replicate previously published clinical studies in which the ASIF was used.


The data of 3 previous 18FFEPPA studies 39 of healthy controls HC, 16 patients with Parkinson’s disease PD and 18 with Alzheimer’s disease AD was reanalyzed with the new approach. PBIF was used with the Logan graphical analysis GA neglecting the vascular contribution to estimate VT. Time of linearization of the GA was determined with the maximum error criteria. The optimal calibration of the PBIF was determined based on the area under the curve AUC of the IF and the agreement range of VT between methods. The shape of the IF between groups was studied while taking into account genotyping of the polymorphism rs6971.


PBIF scaled with a single value of activity due to unmetabolized radioligand in arterial plasma, calculated as the average of a sample taken at 60 min and a sample taken at 90 min post-injection, yielded a good interval of agreement between methods and optimized the area under the curve of IF. In HC, gray matter VTs estimated by PBIF highly correlated with those using the standard method r2 = 0.82, p = 0.0001. Bland-Altman plots revealed PBIF slightly underestimates ~1 mL-cm3 VT calculated by ASIF including a vascular contribution. It was verified that the AUC of the ASIF were independent of genotype and disease HC, PD, and AD. Previous clinical results were replicated using PBIF but with lower statistical power.


A single arterial blood sample taken 75 minute post-injection contains enough information to individualize the IF in the groups of subjects studied; however, the higher variability produced requires an increase in sample size to reach the same effect size.

Author: Rostom Mabrouk, Antonio P. Strafella, Dunja Knezevic, Christine Ghadery, Romina Mizrahi, Avideh Gharehgazlou, Yuko Koshimori, Syl

Source: http://plos.srce.hr/


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