Contents
Lawrence Berkeley Laboratory was formerly known as Lawrence Radiation Laboratory. During the time of the lab studies provided here the lab was not a national lab yet, and so only known as LBL. The national lab status was obtained in 1995, when it became known as Lawrence Berkeley National Lab LBNL. At that time these studies had concluded and the remaining data and tissues were transferred to the National Radiobiology Archives at University of Washington, PNL.
Summary
PI: Dr. Patricia Durbin
Isotopes: neptunium-237, plutonium-237, plutonium-238, americuim-241, and strontium-90
Species: Primates: Cynomolgus, Rhesus (Macaca mulatta), Stumptail, mice
Methods: Injection, intravenous or intermuscular/intraperitoneal.
Purpose: Metabolism studies on primates for understanding of control and distribution.
History
The Lawrence Berkeley Laboratory was founded in 1931 by Ernest Orlando Lawrence, a University of California Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics.
From Chuck Watson (NRA) file called “DURBIN” in “I. Primate materials”:
“Dr. Durbin’s collection of primate materials is unique, and it includes materials shipped to her from a control colony maintained by the late Dr. Gertrude Van Wagenen of the Yale Medical School and from the primate studies conducted by the late Dr. Lawrence Tuttle at the University of Rochester and the Delta Regional Primate Center in Louisiana, as well as materials collected by Dr. Durbin and her co-workers at LBL. Two Macaque species are represented: 157 rhesus and 48 cynomolgus monkeys of both sexes with ages ranging from newborns to senility (at about 30 years of age). The materials from Dr. Van Wagenen are injected normal controls (all rhesus, 48 animals). The bulk of the population (157) animals) were injected with tracer to low-toxicity amounts of 241Am or 238Pu or injected with or fed 90Sr, and two animals were injected with 237Np and one with 233U.”
Electronic and hard copies of the numerical research database were previously transferred to the NRA on September 1990 and September 1992. Not all monkeys had tissues collected, some contributed numerical data only.
Dr. Durbin’s laboratory was demolished in early 1995 that provided a smaller remodeled space that no longer accommodated storage of these studies. This prompted Durbin to turn over the data and tissues the the National Radiobiology Archive except for the preserved monkey bones preserved in 70% alcohol in 100 jars, as recommended by the NRAAC at that time.
The LBL also held historical materials from Crocker Laboratory’s WWII work on radioelement distribution in tissues and bone of rats. These materials consisted of microscope slides of undecalcified bone sections and their contact autoradiographs (72 slide boxes) and original lantern slides prepared by Dr. J.G. Hamilton to illustrate radioelement distributions and localization in the 1930’s. These materials were recommended to be sent to the Tennessee Library Special Collection by the NRAAC.
Monkey Studies Data
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Study Abstracts
Biokinetics of Strontium/Actinides
PATRICIA DURBIN
Our objective is to advance internal radiation dosimetry and radiation protection. Biokinetic models for the element provide the means to calculate radiation dose rates and integral doses in the tissues in which they are deposited. These models and their validity depend on reliable measurements (biokinetic data) of initial element distribution and its retention over time in human tissues. Human data adequate for biokinetic modeling do not exist for the actinides, and it is necessary to rely on data from suitable laboratory animals. Macaca, a genus of Old-World monkeys phylogenetically closely related to man, were the subjects of these experiments. Biokinetic data were obtained from the monkeys after injection of one of the following nuclides: 241Am; 30 adult, I d to 6 y post-injection (p.i.); 238Pu, 27 adolescent and adult, 2 d to 3 y p.i.; 237Np, 2 adult, 4 d and 2 y p.i.; 9°Sr,90 growing and adult, 1 d to 19.5 y p.i. Monkeys were managed individually. Radio analysis of all bones (many subdivided), soft tissues, and excreta, and serial external counting achieved material balances _ 90% of the injected radioactivity. No live animals remain; we have radio analyzed all samples; we are completing reduction and entry of numerical data into the computer archive; soft tissue and most sets of bone autoradiographs are complete. Analysis of the numerical data and autoradiographs will quantitatively describe the initial distributions and temporal changes of the study elements in a laboratory animal that is a developmentally, anatomically, and physiologically ideal substitute for man. We will analyze and publish the archived data from this project and will construct mechanistic models to serve as foundations for improved models of the study elements in man and other animals.
Biological Evaluation of New Actinide-Chelating Agents
PATRICIA DURBIN
Alpha-emitting actinides deposited in bone, liver, or lungs (if inhaled) induce cancer. Complexation by transferring prevents excretion and effectuates deposition in target organs. The only known way to reduce cancer risk is by accelerating actinide excretion with chelating agents. The similar coordination properties of Pu(IV) and Fe(llI) indicate that macromolecules containing four bidentate Fe(III)-binding groups should form excretable Pu(IV) complexes at pH 7 but spare essential divalent metals. Ligating groups of microbial iron-sequestering agents (siderophores)–catechol (CAM), hydroxamate (X), and hydroxypyridinone (HOPO)–are being incorporated into octadentate ligands. Molecular backbones are: aminoalkane LIFESCIENCESDIVISION 59LAWRENCEBERKELEYLABORATORY (spermine, 3,4,3-LI); ethylenediamine (H); triethyleneamine (TREN); desferrioxamine (DFO) to which a fourth group is attached. Solubility and acidity of CAM are increased by additions to the benzene ring: sulfonate, CAM(S); carboxyl, CAM(C); methyiamide, MeTA.M, We evaluate ligands (injected or oral) in mice for promoting excretion of i.v.-injected 23SPu(IV) and for acute toxicity using liver and kidney lesions as endpoint. Among ligands tested, seven promoted more Pu excretion than CaNa3-DTPA at the standard dosage of 30 Ilmole kg”-injected i.p.; nine given orally were superior to CaNa3-DTPA; six left no Pu residue in kidneys (Pu complexes are stable at low pH); six that were tested at 1/10 to 1/3 the standard dosage were still effective for Pu removal, but CaNa3-DTPA is not. Ten ligands and CaNa_-DTPA were ranked for the following: a) Pu removal after injection, b) Pu removal after garage, c) percent injected Pu left in kidneys. In order of combined ranking, ligands with better overall Pu removal than CaNa3-DTPA are: 1) 3,4,3-LI(I,2HOPO); 2) DFO-(1,2-HOPO); 3) 3,4,3-LIMeTAM; 4) 3,4,3LICAM(S); 5) DFO-MeTAM; 6) 3,4,3-LICAM(C); 7) H(2,2)MeTAM. Ligands 2, 4, 6 were tested for removal of 24iAm(III) and 237Np(V); they promoted significantly more Np excretion than CaNa3-DTPA, but were essentially ineffective for removing Am. Ligands 1, 3, 4, 5 were acutely toxic if injected at 1000 µmole kg1 which is 3,000 to 10,000 times their effective dosages. Planned research includes:
- Evaluation of new ligands for Pu removal (syntheses of new ligands containing MeTAM or low-toxicity 2Me-(3,4-HOPO) are in progress);
- Evaluation or reevaluation of acute toxicity of effective ligands using a revised protocol (10 daily injections of 100 µmole kg1, which is 300 to 1000 times their effective dosages);
- Biokinetic studies, including GI absorption, of representative effective free ligands using colorimetry of their Fe(llI) complexes or 3H-labeling and, for some ligands, the 59Fe-labeled ferric-ligand complexes; and
- Evaluation of HOPO ligands for removing Am(III) and Np(V).
Recommended Reading:
Konzen K, Brey R, Guilmette R. Early blood plutonium retention in nonhuman primates compared to the NCRP 156 wound biokinetic model. Health Phys. 2015 Mar;108(3):383-7. doi: 10.1097/HP.0000000000000209. PMID: 25627953.
Lawrence Berkeley National Lab. (LBNL) (1993). Catalog of Research Abstracts, 1993: Partnership opportunities at Lawrence Berkeley Laboratory. https://doi.org/10.2172/10106125
Poudel, Deepesh, Klumpp, John A., Bertelli, Luiz, et al., “Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates,” Health Physics 113, no. 2 (2017), https://doi.org/10.1097/HP.0000000000000675
