Univeristy of California School of Medicine San Francisco, the Radiological Laboratory Semiannual Report December 31, 1956, Atomic Energy Commission Contract No. at-11-1-Gen-10, Project No. 2

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Unclassified Health and Biology University of California School of Medicine, S a n Francisco Department of Radiology f o r period ending December 31, 1956 Atomic Energy Commission Contract No. AT-11-1-GEN-10, Project No. 2

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TABE OF CONTENTS I. Absorbed Dose Calibration 11. Preventive Maintenance Work Age, Growth, and the LD,, of X-Rays Influence of Strain on Acute X-Ray Lethality Acute X-Ray Lethality Studies with the Rat. i n the Mouse. Recovery Rate Studies LD5,, Death Rate, and Recovery Rate Tresuwnt of Patients Enumeration of Blood Platelets

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The six-month period covered by this report i s naturally divided int o three nearly equal parts by changing operations involving the sy-nchrotreated; during the second part, a complete calorimetric recalibration of the 70-Mv x-rays from the synchrotron w a s made and a large amount of preventive maintenance work was done; and during the third part, the treat - ment of cancer patients w a s reinstituted. the major effort of this section has been directed towards improvement i n our therapy technique (new field shapes , back pointer, positioning devices) as well as assisting i n treatment planning, performing the irradiations, and calculating doses delivered i n regions of interest.A routine which is reasonably smooth has not yet been achieved and this sort of acti*y During the first part, a group of patients with cancer wm being During the treatment periods "he method described i n the previous progress report (UCSF-13) f o r determining the dose absorbed in water from an x - r a y beam was used again, This method employs a vacuum cal or be ter to measure the energy content of the x-ray beam and also the energy transmission of t h a t beam through a large water phantom. of the phantom, the difference between the cal or he ter energy mpasurements i s the energy absorbed i n th? phantom. A detailed examination of the distri but ion of local energy absorption, as judged by ionization, leads t o formation of a numerical integral in term of (gram of water) times (per cent of peak ionization in that gram of water), which integral should also represent the energy absorbed in the phantrm. ence (- lo$) i n density effect for ionization observed i n the beam compared with that outside the beam i s necessary t o have all parts of the above inte gral refer to energy absorption in the water rather than t o the ionization actually observed. Apart from a leakage correction out from the sides The primary r e s u l t from the calorimeter is the beam energy density per monitor integration unit. 1956, respectively, gave 0.652 and 0.647 milli,joules/& per monitor unit. For the latter figure, the maxirmrm experimental uncertainty is estimated at 1.29 and the standard deviation at O.@. arises from lack of kuowledge of the air temperature i n the monitoring ionThe determinations of March and October, Most of the uncertainty

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X-ray beams of nominal diameter 3,5 and 5.0 cm are used for the these f i e l d s are 0.674 and 0.727 racl/MU, respectively, at the peak of the depth dose curve. comparing ionization per monitor unit at the peak of several f i e l d s . For example, calling the peak ionization fora 15-cm field 1.000, the rel - ative peak ionization for the smaller fields has been determined t o be 0.722 and 0.780, respectively. Dividing the energy calibration f o r each small field by the relative ionization figure gives 0.934 and 0.931 rad/MU as independent determinations of the energy calibration for the 15-cm The experimental results for These results have been extended t o larger fields by The absolute comparison between energy absorption i n water and cavlty ionization has been determined with an extrapolation chamber. Since the extrapolation chamber could not readily be immersed i n water, measurements with it were actually made i n a Pressclwood phantom and subsequently the ionization response r a t i o (- 1.01)between water and Pressdwood was determined with other, immersibie chambers. Correcting the observed ionization for electrometer scale, for recozbination loss, for conversion t o the peak i n water, and t o 760 mm Hg and 0 ' C., we found i.080 esu/cc per monitor unit. Dividing the above energy calibration by this Selected Victoreen thimble chambers have been irradiated i n the 15-cm beam under a variety of circumstances. by application of a Co60 correction factor and are corrected t o 760 mm Hg and 22 The unit of the corrected reading w i l l here be labelled groups of three a t the peak of the 15-cm beam, with the thb ble centerlines 200 cm from the target)is 0.970 "r" per monitor unit. Readings taken are reduced The average response of five thimbles (exposed in Pressdwocd i n Victoreen thimbles have'also been irradiated a few t be s in a 1/8-in. lead cap and i n an ll.5-cm Lucite cube, as suggested in National Bureau of Standards Handbook No. 55. Table I summarizes the beam energy density needed f o r unit detector response under the circumstances cited. We note a very substantial disagreement, many times repeated, between thimbles with a CosO correction factor. determined by the National Bureau of Standards and have also been compared vith good agreement a t another hospital with factors similarly determined for their chambers. The Coeo corrections have been

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Detector Environment Beam Energy Extrapolation chamber Water The largest single item in this category was the replacement of the vacuum system supplied with a new one. elopment as a backlog job for over a year and was designed for optimum performance and t o fit i n existing space i n the synchrotron. between changing injectors and producing x-rays has been reduced from a previous minimum of 24 hours t o 3 hours, the interlocking system on the new controls is not quite complete. The new system has been under devThe time loss For lack of delivery of one part, Other items i n this category include making spares for special funct ional parts such as the quadrant chamber and a complete "five-year'' servicing such as repacking the ball-bearings of the several electric motors. Experiments aimed at specification of a chemical dosimeter more stable and more sensitive than the conventional ferrous sulfate dosimeter have continued. The concept currently being exploited i s t o protect the ferrous ion by forming a large cmplex ion by addition of an organic acid. Inorganic complexing additives have been tried but generally result in a decrease in sensitivity.

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Simplifying somewhat the situation for the organic acids, those containing an NH, group exhibit decreased sensitivity, those containing = OH s o u p exhibit moderately increased sensitivity, and those containing a COOH group exhibit markedly increased sensitivity. Of the latter group, benzoic acid has been studied most. The sensitivity increases linearly from 1.0 relative to the conventional ferrous sulfate with no benzoic acid t o a stable value of about 3.5 when the molar concentration of the benzoic acid is about 1.5 times that of the ferrous i o n . Thus one might suspect t h a t the complex consists of 3 benzoic acid molecules and 2 ferrous ions. The sensitivity increase may be explaine$ by the close association of OH groups t o the ferrous ion i n the complex and thereby achieving, either by ease of removal of an OH f r e e radical or by simple proximity, an increase i n the probability for iron oxidations. The greater sensitivity of COOH groups than OH groups may indicate hydration of the double bond of t h i s group creating, i n effect, C(OH), and therefore increasing the iocal population of OH groups. The stability of the benzoic acid-ferrous sulfate dosimeter (in1.0N &SO4) is phenomenal. About 20 l i t e r s of one fornulation was mixed ia June, 1956 and is apparently unchanged either in ferric ion content or in sensitivity to date. Small aliquots of it are being irradiated elmost daily to check uniformity of response and technique found with higher sensitivity than that with benzoic acid, bstto date these are not as stable. System have been The mix-and-try method of finding better systems is not currently being used. Instead, measurements have started on afew groups of additives in which some basic structure is common. alcohol, formaldehyde, formic acid, and possibly carbonic acid. The simplest group is methyl The future of this line of endeavor, i n addition t o standardization of radiation measurements and to integral dose measurements, could very well be a better understanding of the role of free radicals i n producing chemical changes and subsequently in producing biological effects. IV. ACTIVITIES BY PERSON William R.Balk well, B.S-, has been entirely concerned with the work in chemical dosimetry. Nicholas McIlwraith, B.S., on a part-time basis, has been continuing the development of a revised radiofrequency system for the synchrotron. This system had one brief and partly successful test on the synchrotron and now appears t o be approaching the desig requirements. Bernice B. Borrman, B.S.,a certified radiological physicist, has joined OUT staff temporarily on a part-time basis. She has been very helpful in the Patient-treatment program. Edtnund Wong as accelerator engineer has had, i n addition t o routine operation and maintenance of the synchrotron, the responsibility of designing, constructing, and installing the controls for the

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new vacuum system. experiments and in improving the therapy technique. of new devices, including the mechanical portions of the vacuum system, and parts of the design have been well done by Henry D. Steier. He has a l s o given very able assistance in the calorimeter All of the construction

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The following f'ull-time investigators participated In the biology imental radiology; Robert F. Kallman, Ph,D., physlology ( p a r t of the perLsso of the 4-Day-Old Chick Embryo. The last of a series of tests 250-kvcp x-rays (KVL, 1.6 mm Cu) was carried out, and the r e s u l t s were found t o be i n agreement with those reported previously (UCSF-12, 1955; the 4-day chick embryo, incubated and irradiated a t about 37 C Seven hours after exposure (tissue-doze rate, 55-6 r/mln) the eggs were cracked open and the embryos examined; those with beating hearts were scored as Kith 95%confidence limits of 950 and 1007 r. This last test involved the detemination of the LD,, of The analysis of the pooled data for six experiments with a total of minations reported previously with bacteria, yeast, and mice, the RBE Reproduclbllitx of the RBE. The chick-embryo test was carried out one year after the first test with Yeast. To determine whether o r not any drift in the estimate of the RBE had occurred dur1.qthis interval, particular tests were repeated from time to time. With a yeast test repeated just after the conclusion of the chick-embryo series in June, 1956, the RRE was 1% higher than i n May, 1955 (Table I ) . dicated a decrease i n the RBE of 2 t o 5% between June, 1955 and January, These fluctuations are considered t o be of minor importance.

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Test Date RBE exposure), weight loss The RBE of the synchrotron x-ray beam was est hated in six trials visiae, haploid), adult CAFl mice, a d the &-day chick encbryo. methods employed were like those I n the 1000-kvcp x-ray de tem nat iom, and have been described io detail (1) . Uncertainties regarding the dos iw try in these trials preclude a precise statement regarding the RBI?,. the results indicate that the REE wilJ he withLn the range reported for other supervoltage beams. have been calculated on the basjs of varlous physical units in order t o illustrate the degree of variation that may be introduced thereby. Grvlting this uncertainty, however, The est i a at es arc given i n Table 11. They

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Tentative RBE Values Dcmen: esu/cc rads rads Test No. of *The synchrotron dosimetry, by Dr. Gall D. Adams, i s dealt with i n the The 250-kvcp dosimetry was carried out t o determine the tissue dose Physics Section of this report. f o r approximately O.l$ of the absorbed energy and therefore is considered according t o the usual procedures. Neutron contamination was estimated t o account Itdose) into rads, as recommended by Gray (Brit. J. Radiol. 29: 355, 1956). is thought that this factor is not more than several per cent in error.

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In the case of x-rays and other ionizing redlatione, the dependence of the acute LDSO on age has not been determined throughout the life-span of a mammal, although it is lmovn that immature mice (1)and rats(2) are more sensitive than mature ones, and it has been Indicated t h a t mature female r a t s are more sensitive a t 16 than at 6 months (3). experiments contribute data for the first 75 to86 of the - 900-day life - span of CAF, mice. The biological, physical, and statistical methods employed have experienced puberty a t about 50 days. Deaths were counted during the 28-day period after a single whole-body exposure. For each LDso determination there were 4 t o 6 dose-groups of about 10 animals each, thus enploylng a t o t a l of about 5 0 animals. The mice were weaned a t about 30 days and 250-The radiation factors were: The results (Fig. 2) showed that the LDs0 was a linear function of log age, A, from 37 t o 105 days, but was practically constant from 115 t o 709 days, Thus the hypothesis that the "adult" LD50 is proportional t o remaining l i f e expectancy ( 5 ) was not confinhed. increased value of 2, the aver- of the LDa/LDso and LDso/LDl= ratios. For ages 600 t o 709 days, three deterainatidns of 2 were 1.16, 1.17, snd terminations of s were 1.072 * 0.024. Radiobiologically, therefore, the population became more Variable a t 600 days. f o r log body weight (Figs. 1 and 21, a parameter of growth. A change occurred in the response of the oldest ,jJshown by the For ages 37 t o 434 dsys, the mean and 6tande;rd &viation of 29 deThe diphasic dependence of the ID50 on log age was similar t o that

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It may be said, therefore, that for the first &'$ of the life-span the LD,, continued to increase until the growth rate fell to its flilly mature level, after which the ID,, remained constant. J. B. Hursh and 0. W. Casarett, Brit. 2. Radiol. 39, 169 (1956). H. A. Blair, hoc. Internat. conf. Peaceflil Uses of Atomic Energy,

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~ i g .1. hog boay weight (gn) 88 a function of log age

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and age ( r o l l & -8). Points without taib ape for both scxm. for the animals ai …