99mTc-DADT complexes substituted with heterocyclic amines: effect of substitution on in vivo reactivity.
Alkylpiperidinyl and alkylpyrrolidinyl 99mTc-DADT complexes were synthesized and tested for their ability to cross the BBB. Each complex was a mixture of two epimers separated by HPLC. More lipophilic epimers were biologically evaluated in mice, at various time intervals. Similar biodistribution patterns were obtained for both piperidinyl and pyrrolidinyl DADT-complexes. Brain uptake or retention was influenced by the heterocyclic amine introduced into the DADT backbone. Subcellular concentration of selected 99mTc-DADT complexes was more profound in crude nuclear and post-microsomal fractions. Moreover, interaction of 99mTc-2,2,6,6,9,9-hexamethyl-4,7-diaza-4-(3-methylpyrroli dinyl)-ethyl-1,10- decanedithiol with either lipids or microsomes of whole brain was almost unaffected by time. This may suggest that a possible selective site of interaction and metabolism for DADT complexes occurs in brain.
Papadopoulos
M
M
Radiopharmaceuticals Laboratory, Institute of Radiosotopes and Radiodiagnostics, NCSR Demokritos, Attiki, Greece.
Stathaki
S
S
Mastrostamatis
S
S
Varvarigou
A
A
Chiotellis
E
E
D000588:Amines / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000588:Amines; D006571:Heterocyclic Compounds; D015609:Organotechnetium Compounds; D013438:Sulfhydryl Compounds