Design of Infusion Schemes for Neuroreceptor Imaging: Application to [(11)C]Flumazenil-PET Steady-State Study.
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.
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Ling
L
Feng
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Claus
C
Svarer
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Karine
K
Madsen
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Morten
M
Ziebell
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Agnete
A
Dyssegaard
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Anders
A
Ettrup
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Hanne Demant
HD
Hansen
PET and Cyclotron Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Szabolcs
S
Lehel
Heart Centre, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus, Denmark.
Stig
S
Yndgaard
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medicine Sciences, Copenhagen University, Blegdamsvej 3, 2200 Copenhagen, Denmark; Danish Research Centre Magnetic Resonance, Copenhagen University Hospital, Hvidovre Hospital, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
Olaf Bjarne
OB
Paulson
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medicine Sciences, Copenhagen University, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Gitte Moos
GM
Knudsen
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medicine Sciences, Copenhagen University, Blegdamsvej 3, 2200 Copenhagen, Denmark; Epilepsy Clinic, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Lars Hageman
LH
Pinborg
D000328:Adult; D002250:Carbon Radioisotopes; D005246:Feedback; D005260:Female; D005442:Flumazenil / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
D002250:Carbon Radioisotopes; D005442:Flumazenil