TY - JOUR

T1 - Design of Infusion Schemes for Neuroreceptor Imaging

T2 - Application to [(11)C]Flumazenil-PET Steady-State Study

AU - Feng, Ling

AU - Svarer, Claus

AU - Madsen, Karine

AU - Ziebell, Morten

AU - Dyssegaard, Agnete

AU - Ettrup, Anders

AU - Hansen, Hanne Demant

AU - Lehel, Szabolcs

AU - Yndgaard, Stig

AU - Paulson, Olaf Bjarne

AU - Knudsen, Gitte Moos

AU - Pinborg, Lars Hageman

PY - 2016

Y1 - 2016

N2 - This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [(11)C]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers.

AB - This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [(11)C]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers.

KW - Adult

KW - Carbon Radioisotopes

KW - Feedback

KW - Female

KW - Flumazenil

KW - Humans

KW - Infusions, Intravenous

KW - Male

KW - Metabolome

KW - Middle Aged

KW - Models, Biological

KW - Positron-Emission Tomography

KW - Sensory Receptor Cells

KW - Time Factors

KW - Young Adult

KW - Clinical Trial

KW - Journal Article

U2 - 10.1155/2016/9132840

DO - 10.1155/2016/9132840

M3 - Journal article

C2 - 27123457

VL - 2016

JO - BioMed Research International

JF - BioMed Research International

SN - 2314-6133

M1 - 9132840

ER -