title: The use of thallium diethyldithiocarbamate for mapping CNS potassium metabolism and neuronal activity: Tl+ -redistribution, Tl+ -kinetics and Tl+ -equilibrium distribution.
abstract: The potassium (K(+)) analogue thallium (Tl(+)) can be used as a tracer for mapping neuronal activity. However, because of the poor blood-brain barrier (BBB) K(+) -permeability, only minute amounts of Tl(+) enter the brain after systemic injection of Tl(+) -salts like thallium acetate (TlAc). We have recently shown that it is possible to overcome this limitation by injecting animals with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC), that crosses the BBB and releases Tl(+) prior to neuronal or glial uptake. TlDDC can thus be used for mapping CNS K(+) metabolism and neuronal activity. Here, we analyze Tl(+) -kinetics in the rodent brain both experimentally and using simple mathematical models. We systemically injected animals either with TlAc or with TlDDC. Using an autometallographic method we mapped the brain Tl(+) -distribution at various time points after injection. We show that the patterns and kinetics of Tl(+) -redistribution in the brain are essentially the same irrespective of whether animals have been injected with TlAc or TlDDC. Data from modeling and experiments indicate that transmembrane Tl(+) -fluxes in cells within the CNS in vivo equilibrate at similar rates as K(+) -fluxes in vitro. This equilibration is much faster than and largely independent of the equilibration of Tl(+) -fluxes across the BBB. The study provides further proof-of-concept for the use of TlDDC for mapping neuronal activity and CNS K(+) -metabolism. A theoretical guideline is given for the use of K(+) -analogues for imaging neuronal activity with general implications for the use of metal ions in neuroimaging.
authors.affiliation: Leibniz-Institute for Neurobiology, Magdeburg, Germany. tim.wanger@lin-magdeburg.de
authors.forename: Tim
authors.initials: T
authors.lastname: Wanger
authors.forename: Henning
authors.initials: H
authors.lastname: Scheich
authors.forename: Frank W
authors.initials: FW
authors.lastname: Ohl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Goldschmidt
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology; D004333:Drug Administration Routes; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013793:Thallium / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects*
chemical_list: D009942:Organometallic Compounds; D004050:Ditiocarb; D013793:Thallium; C026995:thallium acetate; D011188:Potassium