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The Use of Total-Body Counters for the Study of Iron Metabolism and Iron Loss

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The Use of Total-Body Counters for the Study of Iron Metabolism and Iron Loss Postgrad Med J: first published as 10.1136/pgmj.49.573.477 on 1 July 1973. Downloaded from Postgraduate Medical Journal (July 1973) 49, 477-486. The use of total-body counters for the study of iron metabolism and iron loss G. T. WARNER D.Phil. Nuffield Department of Clinical Medicine, The Radcliffe Infirmary, Oxford OX2 6HE Summary therefore conventional counting methods can be used Total-body counters designed for clinical use have including total-body counting of the gamma emis- considerable advantage and application over other sion. 55Fe, whilst having a half-life that permits methods for the measurement of iron metabolism. An long-term studies of iron metabolism, is the most investigation may be performed on an out-patient difficult to detect as it decays by K-capture and basis and the need for faecal collections avoided. yields only X-ray emission of some 6 keV. Methods Although the initial cost of their installation is high, of measurement have been developed using either this can be off-set by the saving of in-patient costs in an argon-filled thin end-window Geiger-Muller (GM) 2 or 3 years of operation. tube (Peacock et al., 1946) or a gas flow counter (Hallberg & Brise, 1960), or a liquid scintillation Introduction counting technique (Dern & Hart, 1961; Jenner & Radioisotopes of iron have been of considerable Obrink, 1962; Perry & Warner, 1963; Eakins & importance in the study of iron metabolism for some Brown, 1965). Total-body counting of this isotope 20 years. The technique has almost completely sup- is not possible. planted the chemical iron balance study which, with The very different characteristic emission of 59Fe by copyright. all the problems associated with the measurement of and 55Fe makes possible a double labelling technique small quantities of iron in biological specimens, was whereby a simultaneous administration of, for in- the only method available to the research worker in stance, two different forms of elemental iron is this field. possible. The two isotopes may be separately deter- The radioisotope techniques allow for a direct mined on a Common counting system (Hallberg, measurement of iron absorption, plasma iron turn- S6lvell & Brise, 1958) or by using separate counting over, red cell utilization, and the localization of iron systems whereby the 55Fe is counted by one of the by surface counting techniques. Ofthese, the measure- methods described and the 59Fe by total-body count- ment of iron absorption and iron loss are of the most ing (Hallberg & Bj6rn-Rasmussen, 1972). http://pmj.bmj.com/ practical importance. The very short half-life and limited availability of During the period which radioisotopes ofiron have 52Fe (t4 = 8-3 hr) limits its application to studies of been generally available, a great deal of effort has short duration (Francois & Szur, 1958). been applied to the design and construction ofvarious forms of counting apparatus and to the experimental Methods of measurement techniques themselves. The effort directed towards In one of the earlier studies (Haln et al., 1939) the the provision of counting apparatus has culminated proportion of an oral dose of labelled iron appearing in the present range of designs of total-body counters in the red cells was taken as a measure of iron on September 30, 2021 by guest. Protected for clinical applications. absorption. For the normal subject some 70% of that The basic principle of any measurement using a absorbed from an oral dose of an inorganic salt is tracer technique is quite simple. A dose of labelled utilized for haemoglobin production. In simple iron substance is administered to the patient, the number deficiency, almost all of that absorbed is incorporated of radioactive disintegrations or 'counts' in unit time into new red cells within a few days following an oral are assessed and, at some later time the number of dose. Therefore, in this situation the measurement of 'counts' excreted or appearing in blood or retained the amount of radioactive iron appearing in the red in the body are assessed. cells can be taken as a reasonable indication of the total absorption. For the normal subject the method Radioisotopes of iron gives only an approximation and always an under- Of the radioisotopes of iron available, 59Fe is the estimation. In more complicated anaemia a greater nuclide most frequently used because the half-life of proportion of the absorbed dose may be stored and 44 5 days is convenient, and because it emits both the figures for red cell utilization may be very dif- medium energy beta particles and gamma radiation, ferent from those for absorption (Callender, 1962). Postgrad Med J: first published as 10.1136/pgmj.49.573.477 on 1 July 1973. Downloaded from 478 G. T. Warner The use, therefore, of this method of estimation of rather than a response independent of the distribu- iron absorption is clearly only applicable to certain tion of the radioactivity in the body. Large volume groups of subjects. Because of this Dubach, Cal- detectors such as Nal (TL) crystals (Rundo, 1958; lender & Moore (1948) introduced measurement in Miller, 1962), plastic scintillators (Burch & Spiers, the faeces of the unabsorbed portion of the dose 1953) or large tanks of liquid scintillator (Anderson which, if the faecal collection is complete, gives a et al., 1956; Christian, Kessler & Ziemer, 1962) were better indication of iron absorption. The red cell used and, to reduce the background count to an utilization may also be determined on the same sub- acceptable level, both the patient and the detectors ject as an independent parameter. were contained in a lead or steel room (Fig. 1). The method of measurement of the 59Fe in these Several workers have applied these counters for iron early studies was by beta counting. A wet digestion metabolism investigations (Price et al., 1962; Saito technique of the blood or faecal sample was fol- et al., 1964) but, in general, the high initial cost and lowed by electroplating of the iron on to copper discs weight was a limiting factor for their more general (Dubach et al., 1948). An improvement in the count- use. However, for clinical measurements, the require- ing technique was the substitution of a sodium ments are not so stringent, since doses of several iodide (TL) scintillation counter for the GM beta microcuries can usually be administered for diag- counter (Oliver, 1953). A sample of blood or homo- nostic investigations; the shielding against back- genized faeces could then be counted without any ground radiation can therefore be reduced. Chalk, prior chemical operations. Homogenization of for example, has been used for the walls of the faecal samples was necessary to ensure an even counting room (Trott et al., 1963; Tappin, 1963). distribution of the activity within the sample In another design, a minimum of shielding has been (Badenoch & Callender, 1954). used, with only the sides and top of the detector Booth & Mollin (1956) described an arrangement shielded (Glass, Clarkson & Burns, 1964; Pircher of thirty-two small GM tubes arranged in a ring et al., 1965). configuration which, using the gamma emission of A fresh approach has been to provide only partial 59Fe, had a geometry which allowed a faecal sample shielding of lead or steel, so arranged that no directby copyright. of up to 500 g to be counted without prior homogeni- background radiation can reach the detector without zation. first passing through the shield. Background radia- Large volume well scintillation counters using a tion entering through the open sides of the shield plastic scintillator have also been described (Warner must be deflected through at least 900 before it can & Oliver, 1962; Cook & Valberg, 1963; Paix, Davis reach the detector, thus losing energy. This scattered & Blagonravoff, 1965). Clapham & Hayter (1962) radiation is then always below an energy level of have used two horizontally opposed Nal (TL) 0O51 MeV (Compton, 1923). It follows that if Nal detectors. These counters also have a response (TL) detectors are used which have the inherent characteristic that is essentially independent of the ability to produce an output which is proportionalhttp://pmj.bmj.com/ distribution of the activity within the sample and to the energy of the incident radiation, it is possible, have the advantage of a higher sensitivity than the by pulse height discrimination techniques, to reject GM ring counter. Although these apparatus considerably improved the counting procedure, the problems associated with faecal collection remain. A method therefore, which obviates the need for such collection and where a on September 30, 2021 by guest. Protected measurement of the retained portion of the dose is i obtained rather than a measurement of the excreted portion, would have considerable advantage and allow the tests to be performed on a wider range of J~ clinical subjects. Such measurements of the radio- activity in the whole subject can be performed by a total-body counter. I Currently, therefore, the counting method of ! t choice is the total-body counter. now Total-body counters Total-body counters were first developed by FIG. 1. A fully shielded room total-body counter with two separate compartments. The detectors in the left- Health Physics groups for the measurement of fall- hand section are sodium iodide crystals and in the right- out and contamination levels in radiation workers, hand section, large plastic phosphors in a 3 r configura- the principal requirement being a high sensitivity tion (Nuclear Enterprises Ltd.). Postgrad Med J: first published as 10.1136/pgmj.49.573.477 on 1 July 1973. Downloaded from Total-body counters and iron metabolism 479 those events below 0 51 MeV. Thus, although only of a high residual activity from a previous tracer limited shielding is used the background count above test, with a consequent poorer statistical accuracy this energy level approximates to that for a fully in the determination.
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