99 owed by y-ray spectrometry over the course of two or Jyree weeks from the time of sampling,* and from the janicilyls of these data, the “zero-time” activites of 2-Pu, 8Ac, “Th, **4Ra, 742Pb, and 7!*Bi, were eal- njated The activity of the parent isotope, 7*°Th, was dicermined at a later time from a measurement by up to 1.64 e-: a¥ spectrometry in a Frisch grid ionization cham- bir. A more complete description of these analytical techniques can be found elsewhere.'’ By these means, k) e-timates were obtained of the in vivo activities of the above-mentioned thorium-series nuclides at the mo- ment that biological activity ccased, i., generally at the moment of death. ‘The full utilization of these techniques required that meusurements of the y-ray spectra be commenced others nein within an hour of the time of sampling. For obvious practical reasons this was not always possible, and hence the results for the shorter-lived daughter products, particularly ?!2Bi, are not as extensive as for the other radionuclides. f this inNormalization of the Activity Measurements ples from: The activities of the various thorium decay prodreceived ucts in a tissue sample at the time of measurement are F reviously, determined by two quite distinct processes. Firstly, in were ob-¢ tl living animal, there is the process of selective ration of ptrunslocation of each respective nuclide from one organ ie Thoro- to unother or to the excreta. This may loosely be 7 difficult termed a “biological process,” though it may depend umber off on nothing more fundamental than the circulation of ter death ithe blood, However, the important point is that it products) ceuses to act at the moment of death, or, for a biopsy the early sumple, at the time at whichit is withdrawn. Secondly, of long- there 1s the purely physical process of radioactive B growth and decay, which continues regardless of »Whether the tissue sample exists zn vive or in vitro. It y through ix the first of these two processes that we wish to underrast. Se- stand, and the second is merely a physical phenometly afterg non that complicates the calculations and interpreta: tion of the measurements. The method of measurement described above allows Jt correction te be applied for radioactive growth and decay occurring between the time of sampling and the tine of measurement. However, this alone is not sufficient, In order to deduce correctly from the radioac(tivity data some measure of the mobility of each decuy product within the body, it is necessary to take arcount of radioactive growth and decay in vivo be{ween the time of injection and the time of sampling. pA hormalization procedure is, therefore, sought by Wich the steady state activity ratio for any daughter- -\lso referred to as “zero-time,” meaning in the case of : 4 “opsv samples, the time of death, and in the case of biopsy vere fol; Suples, the time of removal of the tissue from the body. parent pair can be predicted from measurements at any time after injection, on the assumption that biological processes continue at an unchanged rate. Such a normalization allows a more meaningful comparison of biological transport parameters to be made in patients or animals injected with different batches of Thorotrast, or examined at different times after injection. For the shorter-lived nuclides, **8Ac, 7?*Ra, 7!°Pb, and *!°Bi, the normalization procedure presents no difficulty. The activity ratio for any daughter-parent pair reaches a steady state value (within <2%) in about 6 half-lives of the daughter product concerned. Therefore, the steadystate activity ratios, 77°Ac/**5Ra, *=4Ra/*28Th, 7°Pb/**4Ra, and 7!°Bi/*!2Pb, are given directly by the ratios of the observed activities, pro- vided that the Thorotrast burdenis of at least 3 weeks’ standing (i.e., 6 half-lives of **4Ra). In the cases of 7°8Ra and 7°Th, the problem is more complicated. Jn vitro, as may be seen from Figure 84, their activities relative to *8°Th eontinue to change significantly until about 50 years have elapsed from the time of maufacture of the Thorotrast. Moreover, during approximately the first 10 years, the 7°°Th activity also depends on the initial value of the *°Th/ 232Th ratio. In vivo, therefore, the attainment of a radioactive steady state is likely to take many years, and until then, the expected steadystate ratios, 7?°Ra/ 2322Th and 7*8Th/**8Ra, can only be calculated byreference to their activities in the injection material. Even when these activities are known, the calculations canido TTT] = = 90+ S sot 3 70m $2 = Sy SO-- o L uw =1.00 / oF -O75 ~ 27 + & & SO > = g < 20 re iz r / 20.25 /—— L iol LL _-7” o&=2= 1 0.1 4 7 7 } 4 4 ~ q f 0.50 — — / / ; T = _ 2 < / / i‘ / — 30 \— °o - f 40}; iL co] TS Th228;Th232 AT To Cc ao TTT TITTY 7. / y 209 1.0 / £ — 4 — —-Th228 activity | ---ra228 activity bp peel 10 _ Lt titils 100 TIME IN YEARS SINCE PREPARATION DATE Toy Fic. 84.—In vitro activities of "Ra and “*Th in Thorotrast as a function of time since the preparation date. For *°Th, the dependence of the activity on the initial **Th/™Th ratio is shown. pas