Laboratory of Nuclear Medicine and Radiation Biology (University of California, Los Angeles) Atomic Energy Commission Contract at (04-1) Gen-12

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UNIVERSITY OF CALIFORNIA, LOS ANGELES LABORATORY OF NUCLEAR MEDICINE AND RADIATION BIOLOGY LOS ANGELES, CALIFORNIA 90024 RESEARCH AND DEVELOPMENT PROGRAM

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IN TRODTJ C TORY STA "EMENT i EFFECTS OF RADIATION ON LIVING O?.GANISPlS (06 01 01) Applied Mainnialian Radiobiology (Byfield and Bennett) 1 MOLECULAR AND CELLULAR RADIOBIOLOGY (06 01 02) Bio synthetic Control (Fulco) Deve lopmen t a 1 Regulation (Harary ) Manialian Cell Biology (Cerschcnson) LAND AND FRESH WATER ENVIROXNENTAL SCIENCES (06 02 04) Ecology of the Nevada Test Site (Beatley) 64 Analysis of Ecosystems (Turner) 77 Distribution and Interrelationship of Elements 8 3 Ecology of Desert Arthropods (Edney) 85 in Biological Systems (Alexander) Nutrient and Radionuclide Cycling (Romney) 90 Plant Physiology and Ecology (Wallace) 97 Quantitative Plant Ecology (Wallace) 102 Physiology of Mineral Accumulation in Plants (Lunt) 100 Soil Survey and Characterization (Hale) ' 104

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TABLE OF CONTENTS RADIOLOGICAL G HEALTH PHYSICS & INSTRUXENTATION (06 02 08) Medical. Physics Instrumentation (Cassen) LO 6 Radiation Measurements Program (Huth) 108 NUCLEAR MEDICAL RESEARCH (06 03 01) Clinical Nuclear Medicine (Taplin) 112 Basic Nuclear Medicine (Poe) 120 Radiod ingnos tic Agent Devc iopment (Rob ins on) 130 Biomedical Cyclotron Facility (MacDonsld) 143 Leukemia Biology (Hays and Vredevoe) 149

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LABORATORY OF NUCLEAR MEDICINE AND RADIATION BIOLOGY UNIVERSITY OF CALIFORNIA, LOS ANGELES SAN FRANCISCO OPERATIONS OFFICE Biology and Medicine I RESEARCH AND DEVELOPMENT PROGRAM The overall objectives of the Laboratory of Nuclear Medicine and Radiation Biology may be summarized a s follows: a. Investigation of the effects of ionizing radiation on systems of biological significance and on living organisms. b. Assessment and study of the imrcediate and long term consequences of the environmental radioactivity on flora, fauna, and man. c. Development of beneficial uses of ionizing radiation and radioactive substances i n medicine and biology. d . The conduct of training and educational activities in fields related to the biological and medical aspects of radiation. Decisions on programmatic adjustments made i n the last year or two are being implemented and the impact of these adjustments is reflected in the FY 1973 and FY 1974 budget requests.In view of this,brief comments on all of our programs, a s organized by divisions,with reference to budgetary needs and changes might help to provide perspective. Biochemistry: (Budget Category 06 01 02). This high - quality program remains a t about the status quo, but the return to AEC funding of two permanent staff members temporarily funded from other sources i n FY 1972 will increase costs slightly in FY 1973 and FY 1974. Developmental Cell Biology: (Budget Category 06 01 02). This relatively new program has not expanded t o the level projected when i t was undertaken because of budget limitations. Modest expansion o f support i s required t o firmly establish this program, which i s highly productive and has exceptional promise for important contributions. Environmental Radiation: Top priority has been biology program. A most important development during the past year has been the recruitment of Dr. Eric Edney t o head up this program. Reorientation of the program is now taking place, but a central part of the strategy is recruitment of two additional staff members t o add strength in critical I given i n the last two or three years t o strengthening the environmental I The cost of these recruitments will be partially offset by reductions

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in other programs, but an additional $30,000 will still be required over the Congressional Allocation in FY 1973 if we are to proceed with these plans in an orderly fashion. Nuclcar 1,Iedicine: (!3udgct Category 06 03 01). The aiolnedical Cyclotron became iully ope-rational i n FY 1972. activity in radio p haro ace utica ls and clinical research is taking phce. TO capitalize on the cyclotron, modest increases in this budget area are required. It i s expected that important interaction with the new Radiation Measureinent Division wili develop, beginning i n FY 1973. In supp rt of the capab?-lity, expanded RadFation i3iology: (Budget Categories 00 01 01 and 06 01 02). This important division in the Laboratory has been understaffed and undersupported inthe past due tose vcr e budget stringency. Two additions to the staff have been made on a non-salaried basis with support being mostly inthe form of laboratory space. To provide modest levels of support i n one of the new areas, Dr.Ben a ett ' slate effects program was re oriented into a collaborative program with Dr. Byfield on the effects of ionizing radiation on mammalian an in als and tissue. This program is very productive , although minimally supportcld, and we request a modest increase in FY 1974. Other areas of Radiation Riology have suffered for insufficiency of technical support which we seek t o add inthe FY 1974 budget. Radiation Ncasurcmcnt: (Budget Category 06 02 08). This is a new program initiated this y car, and developed by Mr. Huth. Basic research will be 8 conducted in radiation sensing by physical means. XpplicaCion areas will be i n medicine and i n the area of environmental problems. These programs will interact importantly with other programs i n the Laboratory. It is obviouslv difficult to project accurately the rate of buildup inthe program; hDwever, w e expect a mare rapid development than would be allowed by the Congressional Budget and a r ? th crc fore requesting an increase. will be needed i n PY 1974 t o enable this progrsm t o achieve its objectives. As the above coiments indicate, many excellent programs have been undersupported in recent years. Nevertheless) even within these limitations important changes have ta!cen place and new programs added t o improve t h e capability of thc Laboratory t o continue t o make icp or tant contributions to An additional increase The composition of costs and staffing for FY 1972, FY 1973, and FY 1974, are sumniarized below for the entire Biology and Medicine Program by major categories of expense. FY 1972 FY 1973 FY 1974 Direct Man Years 9 1 3 103 122 Direct Scientific Man Years 80 914 109

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FY 1972 FY 1973 FY 1974 111 Cost Per Man Year Data: (Shown i n Thousands) Cost Per Direct Man Year $ 25.9 $ 26.0 $ 24.6 Cost Per Direct Scientific Flan Year $ 29.3 $ 29.2 $ 27.5 Total Cost and Manpower data for individual research projects are summarized by Biology and Hedicinc Activity categories in the chart on Page iv. detailed cost and manpower data is given i n the individual project statements on succeeding pages. As will be noted i n the individual project statements the method used at this Laboratory for allocating indirect costs to research projects consists of prorating total indirect costs on the basis of the percentage of total direct salary expense that each research group incurs. This method of assigning indirect costs is believed to be sufficiently accurate and appropriate for an organization of our size and relative uniformity of composition. However, under this method of pro ration indirect costs are not specifically identifiable under individual research projects and for this reason, the composition of indirect expense for the total Program is summarized below. Compos ition of Indirect Expense : I Manpower (Shown as Full Time Equivalence): Total Indirect Personnel 36 U: C. Accounting & Purchasing Services 34.6 Total Indirect Costs $ 790.0

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ADDITIOXAL EXPLANATION FOR OPERATING COSTS RESEARCH AND DEVELOPYINT ACTIVITIES SAN FRANCISCO OPERATIO!JS OFFICE BIOLOGY AND EI EDICT NE 1. Contractor : Laboratoryof Nuclear bledicine and Radiation Biology University of California, Los Angeles Contract No.: AT (04-1) GEN-12 3. AEC Budget Activity No.: 4 . Date Prepared: Publications, UCLA Reports 7 . Person ir, Charge: 8.Project Term: From: 1970 To: Continuing FY 1972 FY 1973 FY 1974 LO. c o s t s : FY 1972 FY 1973 FY 1974 * Total indirect expense of the Contract pro - rated among individual projects on the basis of the percentage of total direct salary expense represented by the

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11. PUBLICATIONS DURING FY 1977 Efficiency in Tetrahymena. J. Plant and Cell Physiol. 12, 461-464 (1971). Effects of Cold - Shifts on the Translational cyte s in the Rejection of Tumor Cells. Arch. Surgery '102, 574-577 (1971). Advances in Radiation Therapy. Ann. Int. Med. 75 (l), 97-110 (1971). Evaluation of Hepatic Preservation Techniques Using the Isolated Rat Liver. and Located on the X-Chromosome? Europ. J. Clin. Biol. Res. (In Press). By field, J. E.: Ionizing Radiation and V in cristi ne : Possible Neurotoxic Synergism. Radiol. Clin. Biol. 4l, 129-138 (1972). Vitro Radio sensitization by Chemotherapeutic Agents. Radiol. (In Press). A Direct Radioassay for of Inhibition of Tumor Cell DNA Synthesis by Immune Cells in Gross Virus Induced Leukemia. Europ. J. Clin. Biol. Res.(In Press). cyte Stimulation of Phagocytosis of Syngeneic Tumor Cells. by Cytosine Arabinoside. (Submitted). Induction of Neuroblastoma Differentiation Radiation Repair in Mouse L-1210 Leukemia Cells. (Submitted). Quantitative Aspects of sensitization in Human Cancer Biopsies. 2nd Cong. Europ. Aqsoc. Radiol., Amsterdam, 1971, Excerpta Medica Intern. Cong. Ser. 234, 106 (1971) (Abstract). tion by Cytosine Arabinoside. Induction of Neuroblastonia Different la - Demonstration a t Xth International Conference L-1210 Leukemia Cells.Amer. SOC. Cell Biol., New Orleans, November, 1971, Radiation Repair i n Mouse tion by Cytosine Arabinoside. meeting Amer. Assoc. Adv. Science,Philadelphia, December, 1971 (Abstract). Induction of Neuroblastoma Different i a -

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sion. Proc. Amer. Assoc. Ca. Res. (In Press) (Abstract). tion Repair i n L-1211) Cells. ROC.A mer. Assoc. Ca. Res. (In Press) (Abstract Repair Inhibitors (Type I11 Radiosynergizers) In Vitro. Rad. Res. (In Press) Breaks by Antibiotics and a Normal Metabolite. Rad. Res. (In Press) (Abstract 12. SCOPE OF THE PROJECT The work supported in this section includes several projects directed towards a n understanding of the effects of ionizing radiation on mammalian animals and tissues.It also includes some basic studies on the effects of radiation on cell division in eukaryotes, together with continued studies on the possib le long term effects of radiation damage on neo pl asia and organism surviva: Several aspects of this work are directed specifically towards increasing survival at the animal level.In addition,a portion of the time i s devoted t o improving the results of clinical radiation therapy through a ration a liza - tion of combined radiation therapy and anti - neo plastic drugs by the development of in vitro radio sensitization assays. In aggregate,the various projec: are weighted towards improving the application of radiation at the organism level and t o developing radio protective measures within a technical range which may be realistically applicable at the human level. 13. R.ELATIONSRIP TO OTHER PROJECTS Part of the work being pursued in this project relates closely to other invest gat ions in this division which deal with the mechanisms of radiation damage. . However, we are particularly interested in examining in detail the process of repair of X-ray damage i n mammalian cells, and particularly the effects of various drugs on inhibiting this repair.In other projects being conducted here we are interested in developing means of increasing radioprotec tion (and protection against radio dine tic drugs) through a process w e term "thermal bone marrow expansion. I ' This work necessarily relates to studies being conducted in several of the AEC national laboratories and t o many hema to logical and radio biological studies being done throughout the In other work we are interested in the developmental biology of neuroblastoma cells,particularly in there ver sibi lit y of the malignancy of these cells. Specifically, we are concerned with the tumor-specific transplantation anti - - gens o f these cells and the ro lk of murine C-type viruses i n the malignant transformation of murine neuro blasts. o cer lap several other investigations within the Developmental Biology Division; of the Laboratory, particularly the work of Drs. Herschman and de Vellis. These studies parallel but do notI Finally,weare continuing our work on analysis of the lifecycle of eukaryoti. cells. This particular investigation is in transition. We have almost com- : ple ted the studies on synchronized Tetrahymena and will begin analogous experiments on mammalian cells during the next fiscal year. These studies relate closely to the work on life - cycle analysis being pursued a t several other AEC installations particularly Los Alamos and Argonne. i

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will be the reduction of the perceived background level. This effo will in essence, however, attempt to arrive at detection of nuclear interactions by their time signature,i,e.,in the sub-nanosecond the effects of temperature, light,etc. on the nuclear radiation detection process are minimized. extremenly low level,in vivo counting of even lowest energy radi at me point of emphasis for gaining increased sensitivity To the extent that this becomes possible Applications would liein 13. RELATIONSHIP TO OTHER PROJECTS The project relates to that of Dr. F. Goulding a t Livermore. supported programs at Bat tell e Northwest, Lovelace Foundation, Argonne National Laboratory relate to our proposed program. Laboratory programs i n Nuclear Medicine, Environmental Biology and Radiati Biology will develop. 14. TECHNICAL PROGRESS I N FY 1972 The first two members of this group joined the staff in June, 1972. 15. EXPECTED RESULTS I N FY 1973 This will be the first year of operation of the project.Initial effort will be the recruitment of staff. We expect tosee the following progress made in basic areas : 1. It i s expected that the germanium detector “module” described above w i become operational and several other detectors for special application will have been developed. 2 . Some methods of crystal growth will have been examined and evaluated by the end of the FY 1972. It is expected t h a t a good diagnosis of what element o r imperfection is causing difficulties in detector characteristics will have been made. 3 . Development of fast electronics with moderate energy resolution for high count rate applications will be underway. nanosecond detection for very small signals should be ina good stage of development and some basic measurements should already be completed on the subject to provide guidance for the nextstep s. The theory of sub4. Methods for measurements of trap characteristics should be well setup should be at a better stage of understanding that at present. A routir method of analysis of germanium ingot samples is expected t o be complet Characteristics of traps created by 7irradiation Application research will depend on staffing progress and exploratory research and cannot be specified at this time. 16. EXPECTED RESULTS I N FY 1974 We expect continued progress i n the basic research initiated in FY 73 and application research should be underway on medical and environmental

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ADDITIOXAL EXPLANATION FOR OPERATING COSTS RESEARCH AND DEVELOFMENT ACTIVITIES SAN FRANCISCO OPERATIONS OFFICE BIOLOGY AND MEDICINE - 1. Contractor : Laboratory of Nuclear Nedicine and Radiation Biology University of California, Los Angeles Contract No,: AT (04-1) GEN-12 2'. Project Title : CLINICAL NUCLEAR MEDICINE 3. AEC Budget Activity No. : 4. Date Prepared: 5 . Method of Reporting: Semi-annual and Final Reports UCLA and HARBOR GENERAL HOSPITAL 7. Person i n Charge: …