%0 Journal Article
%T Decreased defluorination using the novel beta-cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET
%A Mahabuba Jahan
%A Olof Eriksson
%A Peter Johnstr£¿m
%A Olle Korsgren
%A Anders Sundin
%A Lars Johansson
%A Christer Halldin
%J EJNMMI Research
%D 2011
%I Springer
%R 10.1186/2191-219x-1-33
%X [18F]FE-DTBZ-d4 was synthesized by alkylation of 9-O-desmethyl-(+)-DTBZ precursor with deuterated [18F]FE bromide ([18F]FCD2CD2Br). Radioligand binding potential [BP] was assessed by an in vitro saturation homogenate binding assay using human endocrine and exocrine pancreatic tissues. In vivo pharmacokinetics and pharmacodynamics [PK/PD] was studied in a porcine model by PET/computed tomography, and the rate of defluorination was quantified by compartmental modeling.[18F]FE-DTBZ-d4 was produced in reproducible good radiochemical yield in 100 ¡À 20 min. Radiochemical purity of the formulated product was > 98% for up to 5 h with specific radioactivities that ranged from 192 to 529 GBq/¦Ìmol at the end of the synthesis. The in vitro BP for VMAT2 in the islet tissue was 27.0 ¡À 8.8, and for the exocrine tissue, 1.7 ¡À 1.0. The rate of in vivo defluorination was decreased significantly (kdefluorination = 0.0016 ¡À 0.0007 min-1) compared to the non-deuterated analogue (kdefluorination = 0.012 ¡À 0.002 min-1), resulting in a six fold increase in half-life stability.[18F]FE-DTBZ-d4 has similar PK and PD properties for VMAT2 imaging as its non-deuterated analogue [18F]FE-DTBZ in addition to gaining significantly increased stability against defluorination. [18F]FE-DTBZ-d4 is a prime candidate for future preclinical and clinical studies on focal clusters of beta cells, such as in intramuscular islet grafts.Dihydrotetrabenazine [DTBZ], derived from the neuroactive pharmaceutical tetrabenazine, is a ligand for the vesicular monoamine transporter 2 [VMAT2] which is expressed primarily in cells associated with the regulation of neurotransmission. It is especially associated with the dopaminergic system, and [11C]DTBZ has previously been used to study, for example, aspects of dementia [1] and Parkinson's disease [2] in the clinic. High VMAT2 expression has also been found in insulin-producing beta cells in the endocrine islets of Langerhans, but not in the exocrine pancreas [3], and the
%K beta cell mass
%K dihydrotetrabenazine
%K PET
%K VMAT2
%U http://www.ejnmmires.com/content/1/1/33