Comparison of 225actinium chelates: tissue distribution and radiotoxicity.
The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N""-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.
Davis
I A
IA
Life Sciences Division, Oak Ridge National Laboratory, Tennessee 37831-6101, USA.
Glowienka
K A
KA
Boll
R A
RA
Deal
K A
KA
Brechbiel
M W
MW
Stabin
M
M
Bochsler
P N
PN
Mirzadeh
S
S
Kennel
S J
SJ
D000186:Actinium / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005260:Female; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D002614:Chelating Agents; D017879:Isothiocyanates; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D000186:Actinium