A simple facility for total body in vivo activation analysis

Technical notes

428

International Journal of AppliedRadiation and Isotopes, 1973,Vol.24, pp, 428-430. PergamonPress. Printed in Northern Ireland

A Simple Facility for Total Body in vivo Activation Analysis (Received 5 January 1973) EVIDENCE is accumulating of the clinical usefulness of total body in vivo neutron activation analysis (TBNAA). (1) Despite the excellent use of existing major facilities either for irradiation or whole-body monitoring in current methods, (2-7) equipment, such as a cyclotron, is only rarely available or accessible for clinical use. A potential limitation on the wider application of the technique is the expense of establishing such facilities ab initio. (s,9~ This communication deals with the practical considerations in establishing a new facility for clinical T B N A A when such major equipment is not available, outlines a fresh approach to the technique and gives a preliminary assessment of the performance of such a facility.

Design Philosophy A m o n g the least expensive high-sensitivity wholebody monitors using sodium iodide detectors are those of the shadow-shield scanning-type (1°-12) and the combination of a scanning irradiation with the scanning monitor using identical linear speeds offered several advantages. The patient would be required only to be supine on a motorised couch, incurring minimal discomfort and distress, while the use of matched scanning speeds would automatically correct for radioactive decay, associated with the scanning procedures, of all induced radioisotopes along the length of the body. I f 14-MeV incident neutrons are used, five clinically important body elements can be measured simultaneously, these being Ca, P, Na, C1 and N. (6) T h e availability of compact sealed-tube neutron generators giving a high output of neutrons of this energy suggested that these sources would be highly suitable, their size being compatible with their use also in a shadow shield. Their relatively low cost m a d e it feasible to employ two sealed tubes, one above and one below the patient, giving a simultaneous bilateral irradiation as the patient passed between them: similarly, the use of two sodium iodide detectors (29 cm dia. × 10 cm deep), again one above and one below the patient, in the shadow-shield whole-body monitor would provide essentially identical geometries for monitoring and for irradiation.

The Irradiation Facility T h e following strict criteria were applied in selecting the neutron generators: (a) high reliability;

(b) adequate neutron output; (c) capability to remain on " s t a n d - b y " and give a preset output within 10 sec of demand; (d) compactness (15 cm diameter x 65 cm length); and (e) simplicity of operation. Philips neutron generators (type PW5320) met these requirements and were adopted. T w o sealed tubes were housed in a shadow shield of novel design constructed from hand-stacked, high-density concrete blocks supported in a steel framework and faced with panels of simulated wood as shown in Fig. 1. The lower generator is located in a concrete-lined hole in the floor while the upper is supported by a steel framework and located in a cavity in the shield roof. T h e complete facility was constructed in an existing laboratory (22 m x 6.25 m x 3 m), minimising cost since the onIy significant structural alteration was the provision of the hole in the floor.

The Whole-Body Monitoring Fadllty An existing shadow-shield whole-body monitor (11) was readily dismantled to allow provision of a leadlined hole in the floor of the laboratory and was subsequently reassembled, with minor modifications, in its original position in the laboratory adjacent to the irradiation facility. T h e lower N a I detector was sited in the hole and the upper in the central turret of the shield. T h e monitor and its location relative to the irradiation facility are shown in Fig. 1. T h e open nature of both systems prevents isolation of the patient from the attendant staff.

Prellm;n~ry Assessment of Perfornmnce T h e consistent and reliable performance of the complete system was reflected in the preliminary results from sequential measurements of calcium in a h u m a n skeleton contained in a water-filled anthropomorphic phantom. (is) T h e overall standard deviation was not significantly different from the statistical standard deviation of 4-2"0 per cent. T h e reproducibility of the neutron generator outputs was particularly noteworthy since, when the measurements were made, flux monitors were not operational and the neutron outputs were determined by using the same settings on the meters of the control consoles. This finding also underlines their simplicity of operation. Each generator, operated from its own console, 48 cm x 53 c m x 38 cm, was preset and placed in the " s t a n d - b y " position: when neutrons were demanded, switching a single control led to the preset output being achieved, with full stability, in about 3 sec, which easily surpassed the manufacturer's guaranteed rise-time. T h e sensitivity of the shadow-shield whole-body monitor was about 1.5-2 times that of a conventional steel room monitor in use elsewhere (4) but was, of

Fig. 1. T h e i r r a d i a t i o n facility (left) comprises two sealed tube n e u t r o n generators, housed in a concrete shadow-shield, one above a n d one below the motorised couch on w h i c h the p a t i e n t lies. A simultaneous bilateral irradiation is achieved. T h e high sensitivity whole-body m o n i t o r (right) utilizes two sodium iodide detectors 29 cm dia. x 10 cm deep housed in a lead shadowshield with s c a n n i n g - b e d geometry. T h e irradiation a n d m o n i t o r i n g facilities are in a d j a c e n t rooms, as illustrated.

428

Technical notes course, less than that of the 54-detector monitor at Brookhaven.(6) As will be discussed in more detail elsewhere, no significant advantage was obtained by the use of premoderator either close to, or remote from, the phantom to provide some initial thermalisation of the incident neutrons. Indeed, the absence of premoderator resulted in a fast neutron fluence with depth in the body relatively more uniform than that obtained by most other workers. C4-s) The results of fluence measurements in a water-filled phantom are shown in Fig. 2. Results from the simultaneous irradiation and sequential monitoring of the head, thorax, lumbar, thigh, lower leg and arm sections of a polyethylene phantom containing a solution of sodium nitrate suggested that an overall uniformity from one part of the body to another of 4-10 per cent could be attained. Preliminary sequential measurements suggest that an r.m.s, error of about 2 per cent or less in total body estimations will be obtainable. The short transfer time of about 1 rain between the irradiation and monitoring facilities proved highly advantageous in the measurement of short-lived isotopes (e.g. aaP(n, ~)~8A1, Tz/2(A1) = 2-3 min) and in reducing the decay of the other induced radioisotopes. Conclusions

The total body in vivo neutron activation analysis facility outlined offers: (a) Little discomfort or trauma to the patient. The systems are open, avoiding isolation and the measurement can be completed in about 40 rain. The measurement of natural body radioactivity including 4°K occupies about 15 rain, irradiation and

429

transfer about 3 min and the remaining time is used for post-irradiation whole-body monitoring. (b) The simultaneous measurement of Ca, P, Na, C1 and N. I n general, nitrogen cannot be measured using radioactive neutron sources because of the lower energy of the spectrum and phosphorus is measured less efficiently than with 14-MeV incident neutrons, although calcium can be measured more efficiently. (c) Economic advantages, since the capital cost of the irradiation facility, including shielding, fluence monitors etc., would have been about ~23,000 at present prices, while the whole-body monitor would have cost about ~14,500, including a 4K store computer in lieu of a pulse height analyser: no large-scale building programme is necessary. These figures can be compared with the cost of a cyclotron, which is about an order of magnitude greater than that of the present irradiation facility (although it is a more versatile tool), or with the cost of radioactive neutron sources, at about ~32,000 or more excluding the source positioning mechanism and shielding, both plus the cost of a whole-body monitor. (d) Simplicity of operation, including a start-up time from "cold" of about 5 min. Unlike a shared major facility, there is no conflict of priorities and dismantling of equipment to accommodate other users requiring the experimental area can be avoided. (e) A performance at least comparable with that of existing, more elegant techniques if the preliminary results presented here are confirmed. Acknowledgements--The authors wish to thank Prof. H. W. WILSONfor his interest and encouragement and Mr. W. J. ANDERSON for his excellent technical assistance. The irradiation facility and support for these studies were provided by a grant from the Medical Research Council which is gratefully acknowledged. KEXTH BODDV

I. HOLLOWAY

--.--.----.---.--'----.--.----.--.----.--

A.

Fast [copper foils]o

--

- - - - = - - - ~ - - - ~ - -- ~ - - ' ~ - - - - a - - - - ~

• -u-

--~-"

±2-1

"A

r.rn.s.

,-7 -I

I

2

[ I I I ~ I 4

6

8

I t , I T I. [ 1 I I IO

12

Depth from lower surfoco,

14

16

Scottish Universities Research Reactor Centre East Kilbride, Glasgow, Scotland

----~----

Thormo[ [sOdium nitrate so[n]o ± 4 . 5 % r,m.$o

O

ELLIOTT

18

[ I

I l

20

22

cm

Fig. 2. Illustration of fast neutron fluence, measured using copper foils, and thermal neutron fluence using Petri dishes (9 cm dia. × 2 cm deep) containing sodium nitrate solution, in the torso of a man-like water-filled phantom 21 cm deep.

References

1. Proc. of a Panel Meeting on in vivo activation analysis. IAEA, Vienna (1972). 2. ANDERSONJ., OSBO~ S. B., TOMLINSONR. W. S. etal. Lancet 1, 1201 (1964). 3. PALMER H. E., NELP W. G., MURANO R. et al. Phys. Med. Biol. 13~ 269 (1968). 4. CHAMBERLAIN M. J., FREMLm J. H., PETERS D. K . etal. Br. med. Jr. 581 (1968). 5. ANDERSONJ., BAXTYEC. K., OSBORN S. B. et al. Symposium on Nuclear Activation Techniques in the Life Sciences. p. 571. IAEA, Vienna (1972).

Technical notes

430

6. CoHNS. H. and DOMBROWSKIC. S. J. nucl. Med. 12, 499 (1971). 7. Com~ S. H., SHUKLAK. K., DOMBROWSKIC. S. et al. J. nucl. Med. 13, 487 (1972). 8. BODDY K., HOLLOWAY I . , ELLIOTr A. et al. Symposium on Nuclear Activation Techniques in the Life Sciences. p. 589. IAEA, Vienna (1972). 9. CAMERONJ. R. Conferenceson Progress in Methods of Bone Mineral Measurement, p. 513. U.S. Department of Health, Education and Welfare, Washington (1968). 10. PALMERH. E. and ROESCH W. C. Hlth Phys. 1, 1213 (1965). 11. BODDYK. Phys. Med. Biol. 12, 43 (1967). 12. BObbY K. Br. J. Radiol. 40, 631 (1967). 13. BODDY K., HOLLOWAY I. and ELLIOTT A. Proceeding of a Panel Meeting on in vivo activation analysis. IAEA, Vienna (1972).

International Journal of Applied Radiation and Isotopes, 1973, Vol. 24, pp. 430-431. Pergamon Press. Printed in Northern Ireland

The Utilization of Commercial Tissue Solubillzers in Liquid Scintillation Counting (Received 30 August 1972)

Introduction QUATERNARYammonium bases are used to solubilize biological materials for scintillation counting,u,2) Recently D t n ~ ca) tested three commercial solubilizers and found that the color-quenching was so severe with certain fluors that the solubilizers could not be employed. We found that for most conditions we were able to get satisfactory results with these solubilizers.

Materials and Methods Hyamlne 10-X and Soluene-100 were purchased from Packard Instrument Co., Downers Grove, Illinois; the NCS was obtained from AmershamSearle, Des Plaines, Illinois. The Triton X-100 was a Rohm and Haas product. All the organic solvents were Certified A.C.S. grade and employed without further purification. Six different solvent combinations were used, toluene or xylene alone or in combination with either methyl cellosolve (ethylene glycol monomethyl ether) or Triton X-100. In combinations two parts of either toluene or xylene was employed to one part of methyl cellosolve or Triton X-100. The scintillators were added at the following rates: (1) PPO and POPOP,

6 and 0-075 g/1., respectively; (2) butyl-PBD, 5 g/1.; and (3) BBOT, 5 g/1. The counting was performed as follows: 10 mg of dried plant residue (previously extracted with 80 ~o methanol) was weighed into a counting vial, moistened with 0"2 nil of water and digested overnight (approx. 19hr) at room temperature in 1 ml of commercial solubilizer. A known amount of standard hexadecane-X4C was added to each vial followed by 10 ml of the scintillation solvent. The counts were obtained in a Mark I, Nuclear-Chicago scintillation counter and a total of 40,000 counts were collected for each sample. The disintegrations/min were obtained by the channels ratio method from a correction curve. ¢4)

Results and Diseusslon The percentage efficiency is very poor particularly when one considers the scintillator solvents containing methyl cellosolve and Triton X-100. However, if one employs the channels ratio method ¢4) one obtains a very good recovery of total activity (see bracketed values in Table 1). The efficiency (un-bracketed values in Table 1) is extremely variable, e.g. toluene and xylene in combination with Triton X-100 and the scintillator BBOT cause extreme color-quenching. The efficiency varies considerably depending on the solubilizer employed and Soluene-100 would appear to be the best choice. Toluene and xylene alone are excellent solvents for counting radioactivity in the solubilizers, as the differences in efficiency show up only when methyl cellosolve and Triton X-100 are employed. PPO and POPOP can be employed quite satisfactorily although the inclusion of methyl cellosolve does appear to cause more color-quenching. However, when butyl-PBD is used, Triton X-100 causes more quenching than does methyl cellosolve. Triton X-100 cannot be used if BBOT is used as here one gets such severe color-quenching that appropriate correetions cannot be made. It will be noted that methyl cellosolve can be used if the dual-channel count ratio is employed.

Snrn~ary The three commercial solubilizers can be successfully counted under the conditions of our experiment except when Triton X-100 is employed with the scintillator BBOT. LESLIE R . WETTER

J. DYcK

Plant Biochemistry Section Prairie Regional Laboratory National Research Council Saskatoon, Saskatchewan, Canada S7 N O W9