[(11)C]UCB-A, a novel PET tracer for synaptic vesicle protein 2A.
Development of a selective and specific high affinity PET tracer, [(11)C]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine VT. A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats.



3-5GBq of [(11)C]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65GBq/μmol. In vitro binding showed high selective binding towards SV2A. [(11)C]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the VT could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [(11)C]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain.



We have developed the novel PET tracer, [(11)C]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400MBq of [(11)C]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline VT values. This will have to be further validated in human studies.
Preclinical PET platform, Uppsala University, Uppsala, Sweden.
Sergio
S
Estrada
Nuclear Medicine & PET, Uppsala University, Uppsala, Sweden; Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
Mark
M
Lubberink
Nuclear Medicine & PET, Uppsala University, Uppsala, Sweden; PET Centre, Uppsala University Hospital, Uppsala, Sweden.
Alf
A
Thibblin
PET Centre, Uppsala University Hospital, Uppsala, Sweden.
Margareta
M
Sprycha
UCB Pharma, Brussels, Belgium.
Tim
T
Buchanan
UCB Pharma, Brussels, Belgium.
Nathalie
N
Mestdagh
UCB Pharma, Brussels, Belgium.
Benoit
B
Kenda
UCB Pharma, Brussels, Belgium.
Joel
J
Mercier
UCB Pharma, Brussels, Belgium.
Laurent
L
Provins
UCB Pharma, Brussels, Belgium.
Michel
M
Gillard
UCB Pharma, Brussels, Belgium.
Dominique
D
Tytgat
Preclinical PET platform, Uppsala University, Uppsala, Sweden; PET Centre, Uppsala University Hospital, Uppsala, Sweden. Electronic address: gunnar.antoni@pet.medchem.uu.se.
Gunnar
G
Antoni
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D000077287:Levetiracetam; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D013552:Swine; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489618:Sv2a protein, rat; D000077287:Levetiracetam; D010889:Piracetam
Epilepsy; Preclinical PET; SV2A; [(11)C]UCB-A