Iodine-125 and fluorine-18 labeled aryl-1,4-dialkylpiperazines: Potential radiopharmaceuticals for in vivo study of the dopamine uptake system

A series of fluorine-18 and iodine-125 labeled aryl-1,4-dialkylpiperazine analogs, derivatives of GBR 12935, were synthesized as radiotracers for positron emission tomography or single photon emission computerized tomography imaging of the brain based on their affinity for the presynaptic dopamine r...

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Bibliographic Details
Published in:International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes Applied radiation and isotopes, 1992-05, Vol.43 (5), p.671-680
Main Authors: van Dort, Marcian E., Kilbourn, Michael R., Chakraborty, Pulak K., Richfield, Eric K., Gildersleeve, David L., Wieland, Donald M.
Format: Article
Language:English
Subjects:
Animals
Brain - diagnostic imaging
Brain - metabolism
Chemistry
Dopamine - metabolism
Exact sciences and technology
Fluorine Radioisotopes
Heterocyclic compounds
Iodine Radioisotopes
Isotope Labeling
Mice
Organic chemistry
Piperazines - chemical synthesis
Preparations and properties
Tomography, Emission-Computed
Tomography, Emission-Computed, Single-Photon
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Summary:A series of fluorine-18 and iodine-125 labeled aryl-1,4-dialkylpiperazine analogs, derivatives of GBR 12935, were synthesized as radiotracers for positron emission tomography or single photon emission computerized tomography imaging of the brain based on their affinity for the presynaptic dopamine reuptake system. High specific activity fluorine-18 tracers were prepared by nucleophilic aromatic substitution reactions; iodine-125 tracers were prepared by isotopic exchange reactions. In vitro competitive binding studies demonstrated that iodine substitution is tolerated in the 4-position of the phenyl ring of the phenalkylpiperazine group. In vivo regional brain biodistribution studies in mice indicated no selectivity of the radioiodinated ligands for the dopamine reuptake site, with striatum/cerebellum concentration ratios of 1. Similar negative results with the new fluorine-18 derivatives demonstrated that in vivo selectivity for the dopamine reuptake site appears to be critically dependent on the carbon chain length between the piperazine ring and the solitary aromatic ring. These studies suggest that development of new radiopharmaceuticals based on the GBR 12935 structure cannot be based solely on considerations of in vitro binding affinities.
ISSN:0883-2889
DOI:10.1016/0883-2889(92)90039-H