[C-11]UCB-A, a novel PET tracer for synaptic vesicle protein 2 A

Estrada, Sergio (author): Uppsala universitet,Plattformen för Preklinisk PET-MRI

Thibblin, Alf (author): Uppsala universitet,Avdelningen för Molekylär Avbildning

Sprycha, Margareta (author): Uppsala universitet,Avdelningen för Molekylär Avbildning

Tytgat, Dominique (author): UCB Pharma, Brussels, Belgium.;Sanofi Aventis Deutschland GmbH, Frankfurt, Germany.

Antoni, Gunnar (author): Uppsala universitet,Avdelningen för Molekylär Avbildning

(creator_code:org_t)

Elsevier BV, 2016
2016
English.
In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 43:6, s. 325-332

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

Introduction: Development of a selective and specific high affinity PET tracer, [C-11]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 V-T. A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. Results: 3-5 GBq of [C-11]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65 GBq/mu mol. In vitro binding showed high selective binding towards SV2A. [C-11]UCB-A displayed a dose-dependent and reversible binding to SV2A as measured with PET in rats and pigs and the V-T could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [C-11]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. Conclusions: We have developed the novel PET tracer, [C-11]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400 MBq of [C-11]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 V-T values. This will have to be further validated in human studies.

By the author/editor: Estrada, Sergio; Lubberink, Mark; Thibblin, Alf; Sprycha, Margare ...; Buchanan, Tim; Mestdagh, Nathal ...; show more...; Kenda, Benoit; Mercier, Joel; Provins, Laurent; Gillard, Michel; Tytgat, Dominiqu ...; Antoni, Gunnar; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Radiology Nuclea ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.