ISSN:
1573-904X
Keywords:
radioactive tracer molecules
;
technetium
;
blood—brain barrier (BBB)
;
permeation
;
log P
;
ECV304 cells
;
brain uptake
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. To check the influence of structuralcharacteristics on theirpermeation through the blood—brain barrier (BBB), a set of radioactive[99mTc]chelates bearing amine groups was synthesizedand tested in vitro as well as in vivo. Methods. Compounds with different log P and pKa values wereobtained by complex forming reactions of [99mTc]pertechnetate withvarying substituents. Transport was studied in rats and mice, as wellas in an ECV304 cell culture model. Results. In vitro higher permeation was found for compounds withelectron attracting substituents in β-position to the amine group (pKavalues 7.4 to 8.3) than for those with more basic amine groups (pKavalues 〉 8.9) even for similar log D pH 7.4. In vivo brain uptake between0.8 and 4.8;pc of the injected dose (ID) per organ was found for theformer, whereas 〈0.4% ID were present for the latter. Conclusions. Three structurally diverse classes of [99mTc]chelatesshowed distinct patterns with regard to brain uptake in vivo and BBBpermeability in vitro which could not be predicted by their lipophilicityalone. The close correlation between the data from rats and mice andthose obtained with cell cultures render the ECV304 cells an attractivemodel for the screening of new compounds.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007598703357
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