Quantification of PET infusion studies without true equilibrium: A tissue clearance correction. Issue 4 (April 2020)

• Record Type: Journal Article
• Authors: Hillmer, Ansel T; Carson, Richard E
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 40:Issue 4(2020)
• Page Start: 860
• Page End: 874
• Publication Date: 2020-04
• Subjects: Equilibrium -- infusion -- modeling -- positron emission tomography -- volume of distribution; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X19850000
• Languages: English
• ISSNs: 0271-678X

Abstract

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( V T ) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the formV T = V T ( A ) / ( 1 + β γ V T ( A ) ), where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and V T(A) is the apparent V T . Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [ 18 F]FPEB, (−)-[ 18 F]flubatine, and [ 11 C]UCB-J. TCC reduced bias in V T estimates for all radiotracers and significantly reduced intersubject variance in V T for [ 18 F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.