Tagging 7 μ monodisperse polystyrene particles with 11C

Tagging 7 μ monodisperse polystyrene particles with 11C

International Journal of Applied Radiation and I*otop~, 1970, Vol. 21, pp. 639-642. Pergamon Press. Printed in Northern Ireland Tagging Monodisperse...

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International Journal of Applied Radiation and I*otop~, 1970, Vol. 21, pp. 639-642. Pergamon Press. Printed in Northern Ireland


MonodispersePolystyrene Particles with

KLAS PHILIPSON, PER CAMNER and JOHN SVEDBERG National Imtitute of Public Health and Imtitute of Hygiene, Karolimka Iusdtutet, Stockholm, Sweden and Department of Radiobiology, Gtmtaf Werner Institute, U p p ~ a Univer~ty, Uplmmla, Sweden

(Rueived 1 May 1970) Monodisperse particles of polystyrene were tagged by irradiation with 50 i e V protons. A specific activity of approximately 100/~Ci/mg was obtained without the individual particles being visibly affected or tending to cluster. Leakage of the tagging nuclide is very alight and the purity satisfactory. The particles of polystyrene tagged with u C are therefore cousidered to give a suitable test aerosol for studies of tracheobronchial deposition and the first hours of lung clearance in man. LE M A R O U A G E DES P A R T I C U L E S M O N O D I S P E R S E S DE POLYSTYR~aNE DE 7/* AVEC DU n O Des particules monodisperses de polystyr6ne furent marquees p a r l'irradiation avec des protons de 50 MeV. On obtint uric activlt6 sp6cifique d'environ 100 pC/mR sam effet visible sur les particules individueIles ni une disposition de se grouper. I1 y a t r ~ peu d'6chappament du nucl6ide de marque et la purer6 en eat suf~ante. Au~i cousid6re-t-on que les pardcules de polystyx6ne marqu6es au n c rendent un a6rosol d'essai convenable aux 6tudes de la d6position trach6obronchiale et des premi6res heures de la d6contamination pulmonaire chez l'homme. M E q E H H E M O H O ~ H C I I E P C H b l X HACTI4~ (7 MHHPOH) IIOJIHCTHPOJIA YFJIEPO,~OM (nC) MoHo~cnepcH~e tlacTnI~I,t noagcTnpo~a 6~nH MeqeH~ o6ay~eHneM npOTOHaMH B 50 ~eraeneKTpOHBOn~T. B~na nonyueHa y~en~maA aHTnBHOCTb IIpn6ansnTezmno B 100 MHHpoRIopH/MP., npnqeM HHRaRoro B2IIIHHHHHa qaCTHHM He H a 6 n m g a n o c s H OHg He IIpoaBH~Inn TOHReH~HH t{ CHOIIIHOIIHIO B rpynrr~. YTeqga Hn0TOHa MOqOHHH 6M~Ia orient, neeiiaqnTe/lI,iiaH, a qHCTOTa ero y~OBHeTBOpHTe~IbHa. I]09TOMy Megeii~ie uC qacTnRM IIOHHCTHpo2Ia CqHTalOTOH llpHro~iihlM ~(HH IICIIMTaHRI~ a 9 p o n o ~ e ~ R~IH H3yqOHHH Tpaxo0{~pOIIXHaJIt~HLIX OTHOH~eHHI~H IIepBt,lX qaCOB o~nn~eHn~ aerRnx qeaoBe~a. M A R K I E R U N G V O N 7# M O N O D I S P E R S E N P O L Y S T Y R O L T E I L C H E N D U R C H XlC Monodlsperse Teilchen ,con Polystyrol wurden durch Bcstrahlung mit 50 McV Protonen marklert. Eine spezifische Activifiit yon etwa 100 pC/mg wurde erhalten, ohne die einzelnen Teilchen sichtlich zu beelnflussen oder zusarnmen zu ballen. Der Leckverlust des markierenden Nuldids ist sehr gering und die Reinheit zufriedeustellend. Man sieht daher die mlt ~lC markierten Polystyro teilchen als ein geeignetes Prtifaerosol an ffir Studien einer tracheobronchialen Ablagerung und der ersten Stunden der Lungenreinigung im Menschen. INTRODUCTION is so short-lived t h a t the s a m e i n d i v i d u a l c a n b e e x p o s e d several times in o n e d a y w i t h o u t t h e PARTICLES a b o u t I p i n size a n d t a g g e d w i t h r a d i o a c t i v i t y from one exposition interfering a r a d i o a c t i v e n u c l i d e a r e b e i n g used to a n w i t h t h e m e a s u r e m e n t o f t h e next. T h i s i n c r e a s i n g e x t e n t in test aerosols for s t u d y i n g t h e d e p o s i t i o n a n d e l i m i n a t i o n o f i n s o l u b l e simplifies t h e s t u d y o f v a r i a t i o n s in t h e course o f l u n g c l e a r a n c e a n d t h e influence o f different p a r t i c l e s i n t h e lungs. (1-4) W h e n s t u d y i n g t h e factors. I n studies on m a n , m o r e o v e r , shortfirst hours o f c l e a r a n c e , i.e. t h e t r a c h e o b r o n c h i a l p h a s e , i t is d e s i r a b l e t h a t t h e n u c l i d e l i v e d nuclides a r e a n a d v a n t a g e in t h e c o n t e x t 639 1


Klas Philipson, Per Gasrmerand John Svedberg

of radiation safety. With a half-life of 20.5 rain. xlC appears suitable in these respects and as a positron emitter it offers a variety of detecting possibilities. This nuclide has been used already, e.g. for tagging red blood cellsAs) There are several advantages to labelling by means of the irradiation of complete particles. Besides being simple the technique permits more stringent control of the particles and does not involve such large amounts of radioactivity as many other labelling methods. Four factors are particularly relevant to the assessment of methods for tagging particles that arc to be used for test aerosols in studies of deposition and clearance in the lungs: (1) specific activity, (2) the effect of the irradiation on the particles, (3) leakage of the tagging nuclide from the particles, and (4) the purity of the radioactive nuclide.

The number of singlets and multiplets was then counted directly on the slide in a conventional light microscope, each count comprising 300-500 particles. Leakage was tested by leaving the irradiated particles to stand for 1 hr in physiologic saline, 0.1 NHC1 and thanol respectively, after which they were filtered through a millipore filter with pores of 1.2 p. The activity in the filter and the filtrate was then measured. The purity of the radioactive nuclide was studied by following its decomposition in a NaI well counter. The activity was estimated either in this well counter or with two 3 x 2 in. NaI crystals, using coincidence-coupled photomultipliers. In both cases the detector was calibrated with an DNa standard.

RESULTS Specific activities up to 220pCi/mg polyMATERIALS AND METHODS styrene particles were obtained with an 0.55 pA; A somewhat modified version of the spinning- proton beam (see Table 1). Such a high disc technique used by HoLm~(x) was used to beam current turned the particles rather produce the particles, 0.5 per cent polystyrene brown and macroscopic clustering was observed dissolved in xylene being run into adisc 25 m m i n even after ultrasonic treatment. No such dia. revolving at 32,500 rev/min, to give parti- clustering was noted with weaker beam currents, cles 7 p in dia. (standard deviation 8 percent). the frequency of multiplets was not increased Irradiation of the particles was undertaken (cf. Table 1) and no microscopic changes were with the internal beam of the synchrocyclotron detected in the particles. Pictures of irradiated at the Gustaf Weaner Institute in Uppsala. (s) particles taken with the scanning electron During this process the following reaction microscope are shown in Fig. 1 (note that the pictures are ofa vaporised suspension of particles takes place in the particles: and that the formation of aggregates has nothing p + lsC--*lxC + p + n . to do with any such formation in the test The 11C probably binds covalently to the aerosol). Along with the specific radioactivity polystyrene by means of hot-atom or radical it is interesting to note the maximum concenreactions, m A proton energy of 50 MeV was tration of particles that can be sprayed up used and irradiation lasted 30 rain. During irradiation the particles lay in an aluminium TABLE 1. Specific activity and frequency of ringlets cylinder 6 mm in dia. and 20 m m long. The and multiplets after irradiation with different beam cylinder was half embedded in a copper plat, currents (0.2 ml of a suspension of irradiated particles in ethanol was sprayed up) which was cooled by circulating water at a temperature of 8°C. Beam Spec. % i n % i n %in After irradiation, the particles were studied current act. Cone. sing- doub- trip in a light microscope and a Cambridge scanning (pA) (#Ci/mg) (mg/ml) lets lets lets electron microscope. Their tendency to cluster 0-55 220 macroscopic clustering was investigated by suspending the irradiated 0.45 160 6.6 91 8 I particles in ethanol, treating them with a 0.40 120 5.8 87 10 2 Narda ultrasonic vibrator and spraying them 0.35 190 3.0 97 3 0 with a Grafo type II B airbrush up into a 0.30 85 8-4 90 10 1 10-1. glass tower, whereupon a glass slide was 0.25 65 4.5 94 6 0 placed in the tower and left there for 15 rain.

Taggi~ 7 I~monodis~sep o l y s ~ t~r~iel~s with lzc


Counts//5 rain

e o













~ "~


FIo. 2. Decay of the radioactivity in irradiated polystyrene particles. without substantially increasing the frequency of multiplets. A series of determinations of this frequency is shown in Table 2 for non-irradiated particles suspended in different concentrations in ethanol. The frequency of multiplcts increases steadily with the concentration but it seems acceptable to use up to 30 mg particles per ml ethanol.

Table 3 shows the results for leakage of zlCl from the particles suspended in physiologic saline, 0.1 NHC1 and ethanol respectivdy for 60 rain. The leakage is very slight and appears to be somewhat greater in alcohol than in the other two suspensions. Figure 2 shows how the radioactivity in irradiated particles decreases with a half-life


Klas Philipson, Per CaLmer and John Svedberg

TAm2Z 2. Frequency of multiplets among nonirradiated particles suspended in various concentrations in ethanol Cone. mg/ml 0.3 1.6

4-2 5.8 10.2 11.5

15.0 17.8 30-6 35.6

ml sprayed up 0.5 0.5 0.25 0.2 0.2 0.2 0.2 0-2 0.15 0.2

% in % in % in larger sing- doub- aggregates lets lets than doublets 97 97 94 95 92 93 93 91 89 88





4-5 4-8 5.9 5.5 6.0 8-2 9.3 10.1

0-5 0.2 2.3 1.5

1.0 1-0 1.7 1.9

TABLE 3. Activity in the filtrate as a percentage of the activity in the filter (millipore, pore size: 1.2 #) after the particles had been left to stand in the liquid for 60 min before being filtered Physiologic saline


0.1 N HCI Ethanol

0.04% 0"25%

of approximately 2 0 m in but flattens out somewhat above the background level, indicating the simultaneous presence of at least one nuclide with a longer half-life than ItC. After 10 hr, however, the activity is only about 0.003 per cent of the level at the end of irradiation. DISCUSSION The results indicate that polystyrene particles tagged with 11C should bc suitable for test aerosols in the study of pulmonary deposition in particular, but also of tracheobronchial clearance. The specific activity is sufficientlyhigh to permit external measurement (with a suitable apparatus) of the course of lung clearance for a couple of hours-which is long enough in m a n y cases---afterthe deposition of a few tenths of a milligram. T h e particles do not appear to be affected by the irradiation, leakage is very slight and the purity satisfactory. Since the particles are suspended in ethanol, this is included as a gas in the test aerosol. Experiments on the rabbit ts~ have

shown, however, that ciliostasis is induced only by very high concentrations of ethanol in the inhaled air, at least 12,000 p p m during 30 rain. I t should be possible to increase the specific radioactivity somewhat by using higher b e a m currents in conjunction with more efficient cooling. T h e Uppsala cyclotron, however, normally gives only about 0.5 #A. T h e specific activity varies considerably between different irradiations, no doubt in part because the particles occupy only a very small p a r t of the aluminium capsule and the cross section of the main part of the b e a m is small in relation to the surface of the capsule. A container of a different shape and preferably mobile to facilitate stirring should, if combined with a suitable disperser, permit higher a n d more uniformly distributed activities. I t should then also be possible to avoid the changes observed in the particles after irradiation with 0.55/~A. This method of tagging is of particular interest because in principle it should permit the labelling of any particles with n C irrespective of how they are produced, provided they have a sufficient content of carbon atoms. I t thus affords a potential chance of studying deposition and tracheobronchial clearance for particles within a very wide range of sizes. Acknowledgement--This study was supported in part

by Public Health Service grant AP 00212. REFERENCES 1. HOLMAB. Acta med. Stand. 473, 1-102 (1967). 2. MORROWP., GIBB R. and GAZXOOLYK. Am. Rev. resp. Dis. 96, 1209-1221 (1967). 3. ALBERTR. ]~., LIPPMANM. and BRISCOEW. Arch. env. Hlth 8, 738 (1969). 4. BOOKER D. V., CRAMBERLAmA. C., Rum)o J., Mum D. C. and THO~aSONM. L. Nature, Lond. 215, 30 (1967). 5. LARSSONB., GRAFFMAN S. and JuNo B. Nature, Lond. 207, 543-544 (1965). 6. el. LARSSONB. Br. J. Radiol. 34, 143 (1961). 7. STENSTROM T. O n the Chemical Fate of Nascent xzC Atoms Induced by Irradiationof Water and Aqueous Solutionswith 185 M c V Protons. Thesis, Uppsala University (1970). 7. DALHAMNT., HOLMA B. and TOMENIUS L. Acta pharmac, tox. 25, 272 (1967).