The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.
With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.
National Radiological Protection Board, Didcot, Oxon, UK.
G N
GN
Stradling
S A
SA
Gray
M
M
Ellender
J C
JC
Moody
A
A
Hodgson
M
M
Pearce
I
I
Wilson
R
R
Burgada
T
T
Bailly
Y G
YG
Leroux
D000280:Administration, Inhalation; D000576:Americium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D001822:Body Burden; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000528:radiation effects; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D004369:Pentetic Acid / Q000494:pharmacology*; D011005:Plutonium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats
D000577:Amides; D001372:Aza Compounds; D011728:Pyridones; C076998:N,N',N'',N'''-tetra(1,2-dihydro-1-hydroxy-2-oxopyridine-6-carbonyl)-1,5,10,14-tetraazatetradecane; D011005:Plutonium; D004369:Pentetic Acid; D000576:Americium