Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.
OBJECTIVE
To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA).


METHODS
Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium.


RESULTS
The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully.


CONCLUSIONS
The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.
Helmholtz Zentrum München, Research Unit Medical Radiation Physics and Diagnostics , Neuherberg , Germany.
Manuel
M
Kastl
Augusto
A
Giussani
Eric
E
Blanchardon
Bastian
B
Breustedt
Paul
P
Fritsch
Christoph
C
Hoeschen
Maria Antonia
MA
Lopez
D000465:Algorithms; D000818:Animals; D001842:Bone and Bones / Q000528:radiation effects; D002614:Chelating Agents / Q000737:chemistry / Q000627:therapeutic use; D015913:Chelation Therapy / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000528:radiation effects; D008099:Liver / Q000528:radiation effects; D004369:Pentetic Acid / Q000737:chemistry*; D011005:Plutonium / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012984:Software; D014168:Transferrin / Q000378:metabolism
D002614:Chelating Agents; D014168:Transferrin; D011005:Plutonium; D004369:Pentetic Acid
Biokinetic modeling; DTPA; actinides; chelation; decorporation; plutonium