1976, British Journal of Radiology, 49, 568-569 Correspondence Research Grant No. CA-13747 from the National Cancer Institute. Yours, etc.,

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R. E. DURAND.

University of Wisconsin Medical School, Department of Human Oncology and Radiology, Radiobiology Laboratories, Madison, Wisconsin 53706.



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J. E. BIAGLOW.

Case Western Reserve University, Division of Radiation Biology, Department of Radiology, Cleveland, Ohio 44106.

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R. M. SUTHERLAND.

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The Ontario Cancer Foundation, London Clinic, Victoria Hospital, London, Ontario, Canada N6A4G5.

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REFERENCES

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BIAGLOW, J. E., and DURAND, R. E., 1976. The effects of

nitrobenzene derivatives on oxygen utilization and radiation response of an in vitro tumor model. Radiation Research 65, 529-539.

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BIAGLOW, J. E., FERENCZ, N., and FRIEDELL, H. L., 1970.

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A metabolic control for the enhancement of radiation response. American Journal of Roentgenology, Radium Therapy and Nuclear Medicine, 108, 405-411.

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30 TIME (MIN)

DURAND, R. E., and BIAGLOW, J. E., 1974. Modification of

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FIG. 2. Cytotoxicity (closed symbols) and radiosensitizing effect (open symbols, cellular survival after a dose of 1,800 rad) of indicated concentrations of NDPP as a function of time of pre-irradiation incubation with the drug. The upper broken line represents cell survival of untreated spheroids after 1,800 rad; the lower broken line is the survival obtained for fully reoxygenated cells prepared by trypsinizing the spheroids prior to irradiation.

injection techniques. Between these extremes, agents may exhibit both concentration- (NDPP, Figs. 1 and 2) and time-dependent (Fig. 2, and Sutherland and Richardson, 1974) effects. Some agents {e.g. Flagyl) may also selectively kill non-cycling cells (Sutherland, 1974). These effects, including inhibition of oxygen utilization, killing of hypoxic cells, and radiosensitizing properties will make it difficult to determine the exact mechanism of sensitization of such agents in vivo. However all of these properties would appear to be desirable in choosing a sensitizer for tumours. Our results and those of Rauth and Kaufman thus indicate that radiosensitizing chemicals may have "secondary" properties which modify their net effectiveness in vivo. Specifically, effects on oxygen utilization may modify the radio-response of multicellular systems by modifying the size of the hypoxic fraction. As a consequence, we feel that it is unlikely that any hypoxic-cell radiosensitizer which stimulates oxygen utilization will be particularly effective in vivo. In the spheroid system, at least, the effects on oxygen utilization have generally been found to dominate (Biaglow and Durand, 1976). This is not surprising, in view of the fact that molecular oxygen is the most effective radiosensitizer known for hypoxic cells. ACKNOWLEDGMENTS

Flagyl was a gift of Searle Co. NDPP was supplied by G. E. Adams and the NF-167 was given to us by J. D. Chapman. This investigation was supported in part by Ontario Cancer Foundation Grant No. 227, and by Public Health

the radiation response of an in vitro tumour model by control of cellular respiration. International Journal of Radiation Biology, 26, 597-601. RAUTH, A. M., and KAUFMAN, K., 1975. In vivo testing of

hypoxic radiosensitizers using the KHT murine tumour assayed by the lung-colony technique. British Journal of Radiology, 48, 209-220. SUTHERLAND, R. M., 1974. Selective chemotherapy of noncycling cells in an in vitro tumor model. Cancer Research, 34, 3501-3503. SUTHERLAND, R. M., and RICHARDSON, J., 1974. Radiosensi-

tization of chronically hypoxic cells in multicellular spheroids. Radiation Research, 59, 159. THE EDITOR—SIR, WHEN ARE FUME-CUPBOARDS NECESSARY IN HOSPITAL RADIOISOTOPE LABORATORIES?

In a recent letter, Dr. Moore questions the necessity for equipping hospital radioisotope laboratories with fumecupboards "unless the procedures involved are exceptionally hazardous" (Moore, 1975). A considerable expenditure is being incurred unnecessarily if these fittings are provided where there is no real need, and therefore guidance as to what constitutes "exceptionally hazardous" work would be very valuable. The responsibility of making a decision as to whether a fume-cupboard is necessary or not in any new or modified radioisotope department must rest with the local Radiological Protection Adviser (Code of Practice, 1972) who will judge the various factors involved in the light of his experience. Factors to be considered will include the type of department, the work to be undertaken there, the staff to be involved, and a guess as to the work which may become necessary in the future. The local pharmacist will advise on matters relating to sterility of materials for injection. It is unlikely that the many hospital departments which nowadays use radioisotope methods in their own fields will each need a fume-cupboard, though all those which perform in vivo procedures will require a supply of sterile materials. In certain departments the use of an aseptic cabinet may be all that is necessary, e.g. during the labelling of blood cells or plasma. This cabinet will be rather similar in appearance to a small fume-cupboard, but there is no requirement for an air-flow and exhaust system so that the cost is relatively trivial.

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1976, British Journal of Radiology, 49, 569-570

Correspondence In many X-ray departments where radioisotope scanning is undertaken a considerable quantity of radioactivity, mainly short-lived " T c m and 113 In m , will be used. Generators of these isotopes are supplied in a sterile condition and require repeated aseptic elution. The sterility requirements are best satisfied by a closed elution system where the isotope is never exposed to the free air, so that again a fume-cupboard with air-flow and exhaust system may not be required under normal conditions. Tests in this hospital have shown, however, that small quantities of radioactivity may be released through the air-bleed needle which is fitted to the final collecting-vial. The vapour or aerosol emitted can be trapped in a small piece of cotton wool placed around the outlet of the air-bleed needle, otherwise the elution procedure must be done inside the fume-cupboard. It would be preferable to draw the eluent through the generator using a partially evacuated collecting-vial or another syringe. There are an increasing number of departments which undertake the preparation of sterile radiopharmaceuticals for organ imaging, using a selection of the many recipes that have been published in recent years. It is not always possible to use Millipore filters for sterilization of the final product (e.g. in the case of technetium-sulphur colloid) and often the final sterilization is conveniently and satisfactorily carried out using a domestic pressure-cooker (Pearson, 1971). If the slightest amount of radioactivity remains on the outside of a vial, for example, where the rubber cap has been pierced by a hypodermic needle, contamination of the water vapour inside the pressure-cooker will occur and radioactivity will be present in the emitted steam. Such sterilization, therefore, is best performed inside the fume-cupboard. Storage of therapeutic quantities of 131 I, because of the volatility and high radiotoxicity of this nuclide, requires a well ventilated area, and the Code of Practice suggests that a lockable fume-cupboard may be the best place for storing this radionuclide. Dispensing and administration of therapeutic doses of radioiodine should also be performed, in my view, in a well ventilated area or fume-cupboard. Airborne radioactive contamination may also arise when disposable syringes fitted with small-bore hypodermic needles are used to dispense radioisotopes. The use of such needles can easily result in aerosol sprays being produced, particularly when the syringe is almost emptied. When this method is employed, other than into a sealed container, the syringe should be emptied with the tip of the needle below a liquid surface or touching the side of the receiving vessel. There might be justification therefore for the installation of efficient fume-cupboards (Hughes, 1974) in hospital laboratories that are routinely concerned with the elution of isotope generators, the sterilization of radio-pharmaceuticals involving the use of a pressure cooker, and the storage and handling of therapeutic quantities of 131 I. I believe it is true that Madame Curie, rather fortuitously, occupied a laboratory that was no more than a draughty wooden shed when she extracted radium from pitchblende ore. Although I do not advocate that hospital radioisotope laboratories are set up in similar accommodation, it would appear that the copious general ventilation of isotope rooms is perhaps better than the too frequent incorporation of unnecessary fume-cupboards. Yours, etc.,

fume-cupboards. British Journal of Radiology, 47, 888892. MOORE, R. D., 1975. Containment of unsealed sources of radionuclides in hospitals. British Journal of Radiology, 48, 410. PEARSON, J. D., 1971. Procurement and preparation of

radioisotopes and labelled compounds. In Radioisotopes in Medical Diagnosis. Edited by E. H. Belcher and H. Vetter, pp. 218-235 (Butterworths, London).

THE EDITOR—SIR, RADIATION EXPOSURE RATES ON SYRINGE SURFACES FROM 9«>Tcm

A recent article (Henson, 1973) considered possible skin doses and dose-rates from unshielded plastic syringes containing radioactive liquids. In private correspondence, Husak pointed out that the results given for " T c m differed significantly from his own published data (Husak, 1971). This letter contains the results of a subsequent comparison of measurements of surface exposure-rates and calculations, and may be of interest to others who have noted the range of values reported in the literature. Measurements of surface exposure-rate over the midpoint of the syringe active volume were made by two of us (V.H. and J.T.) using LiF-Teflon thermoluminescent dosimeters (TLD). Two discs 0-4 mm thick by 13 mm diameter were taped to syringes, the volumes, inner and outer radii of which were: 2 ml. (4-7 mm, 5-2 mm), 5 ml. (6-0 mm, 6-8 mm), 10 ml. (8-0 mm, 8-8 mm), 20 ml. (9-9 mm, 10-7 mm). The TLDs were calibrated with X rays having mean energy of 45 keV (70 kV+0-5 mm Cu) by using a method for energy dependence calibration developed at the National Personnel Dosimetry Laboratory, Prague. Read-out was made with a Teledyne Isotopes 7100TS reader using pure nitrogen. The TLD's were annealed by a standard method including 24 hours at 80°C before irradiation. The standard measurement was less than ± 5 deviation for one exposure per cent. The " T c m activities were calibrated in a Capintec well ionization chamber and had an estimated accuracy of better than ± 5 per cent. According to our measurements of the energy dependence of TLDs the difference in their response to 20 keV and 140 keV photons of 99Tcm and that to calibration X rays is less than 10 per cent. This result is in agreement with data of Cameron et al. (1968). The experimental results are shown in Table I together with values calculated by the methods of Henson (1973) and Husak (1971). It can be seen that those due to Henson are in better agreement with experiment than those of Husak, but both methods underestimate equally for the full 20 ml. syringe. Possibly, for this large syringe, some allowance is required for scattered radiation build-up, though this was omitted from all the calculations. A more complete picjture is given in Fig. 1 which shows curves of the variation of surface exposure-rate with the volume injected. These were calculated by the method used by Henson and include a curve for a 1 ml. syringe (2-3 mm i.d., 3-3 mm o.d.) for which measurements were not made. Experimental points from Table I have not been added to the curves to retain clarity in the region where the latter are very close. Exposure J. L. BIRKS. rates, for example, for 5 ml. in 5, 10 and 20 ml. syringes are within ± 5 per cent as a result of the geometries of the Department of Medical Physics, various source configurations. As small volumes are apSingleton Hospital, proached, the curves for 5, 10 and 20 ml. syringes approach Sketty, Swansea SA2 8QA. asymptotically the value of exposure-rate from an infinitely thin disc source containing 1 mCi. In practice, of course, as the syringe is emptied the surface exposure rate R, REFERENCES 1 Code of Practice for the Protection of Persons against Ionizing in mR.min.- , falls to zero with decreasing volume according Radiations arising from Medical and Dental Use, 1972. to R=vCRv where Rv is the exposure-rate per mCi at volume v ml. given by the appropriate curve, and C is the (H.M.S.O., London.) 1 HUGHES, D., 1974. The design and installation of efficient concentration of activity in mCi. ml" .

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Letter: When the fume-cupboards necessary in hospital radioisotope laboratories?

1976, British Journal of Radiology, 49, 568-569 Correspondence Research Grant No. CA-13747 from the National Cancer Institute. Yours, etc., _ 1.0 —A...
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