BASIC SCIENCES

A NewOsmium-191/Iridium-19imRadionucide GeneratorSystemUsing Activated CarbonC. Brihaye,* T. A. Butler, F. F. Knapp, Jr., M. Guillaume, E. E. Watson, and M. G. Stabin

Nuclear Medicine Group, Health and Safety Research Division, Oak Ridge National Laboratory, OakRidge, Tennessee; Centre Recherches Cyclotron, Universite de Liege, Belgium; andRadiopharmaceutical Internal Dose Information Center, Oak Ridge Associated Universities, OakRidge, Tennessee

A new osmium-191/iridium-191m (l9bOsf@9lmlr)radionuclide generator system has beendeveloped based on the adsorption of K20sc16(Os-IV)on 140-230 mesh heat-treated activatedcarbon. The generator is OIUIOdwith pH 2 saline solution containing 0.25 g/l KI to give l9lmIr ingood yield. The generator eluent is neutralized to physiologic pH and isotonlcfty with Tris bufferimmediately prior to i.v. injection. No scavenger column is required. As an example, elution of theprototype generator with a 2-mI bolus results in elution of l9lmlrin -“18%yield with an 191@breakthrough of only 2 X iO@ % /bolus. The prototype generator has cOnsiStentperformanceover a 2-wk period with no change in l9lmlr yield or 191Ø@breakthrough. Loading of up to 1.5 Ci of191Ø@ results in no observed rediolysis. Continuous elution of this system is also possible wtth a

mean l9lmlr@ldof 3.7%/mlanda mean 191Ø@@ 2 X 105%/n@lataflow rate of12 mi/mm. This new system represents a readily available source of isimIrfor radloangiography.Adsorbed radiation dose calculations indicate a total-body dose of only 3.9 mrad for a 100 mCiinjected bolus.

J Nucl Med 27:380—387,1986

ridium-191m (l9lmIr) (4.96 sec) is obtained from anosmium-191 (‘910s)(1 5 days—fi decay) generator andemits x-rays (63 keV-l6%, 65 keV-28%, 74 keV-12%)and a gamma-photon (129 keV-26%) that can be detected with conventional gamma cameras. The very lowradiation dose and opportunity to perform rapid, repeatstudies make this system very attractive in comparisonto other single photon generator-derived radionuclidesthat are available for radionuclide angiography (1,2).A description of an 1910s/l9lmIr separation by ion cxchange techniques was published in 1956 (3). Later, agenerator designed for medical purposes was developedwhich used the AG1X8 anion exchanger resin as OsCl6ions adsorbent but this system was not pursued forclinical studies (4,5). Hnatowich et al. described a generator constructed by adsorption of hexachloroosmate

Received Mar. 12, 1985; revision accepted Nov. 11, 1985.For reprints contact: F. F. Knapp, Jr., PhD, Nuclear Medicine

Group, Oak Ridge National Laboratory, P.O. BoxX, Oak Ridge, TN37831 or C. Brihaye, PhD, Centre Recherches Cyclotron, Universitede Liege,4000 Liege,Belgium.

* Presentaddress:Universite de Liege, Belgium.

on AG1X4 resin in which l9lmIr was eluted with asolution of 8.7% NaC1 at pH 2.2 (6—8).The latestdesign of this generator, first described in 1980, employs the AGMP-l resin loaded with osmium(VI)(9,10) that utilizes a pyrocatechol “scavenger―columnto trap the majority of the ‘910sbreakthrough. Iridium-191m obtained from this system has been usedeffectively for the evaluation of intracardiac shunts inchildren (11,12) and for the determination of left yentricular ejection fraction in adults (13,14). An alternative generator system incorporating malonic acid in theeluent solution was recently described by Packard et al.The system showed good l9lmIr elution yield (30-35%)and low 191Ø@breakthrough (3 X 10@%) but the authors observed a more rapid decrease of the yield as afunction ofthe time than with the previous system (15).

Because of the rather complicated fabrication of theAGMP-l generator system and the relatively shortuseful life due to decreasing l9lmIr yields and increasing19105 breakthrough (9), other potential 1910s/l9lmIr

generator systems have been evaluated. Since l9lØ@isreactor produced, and has a 15-day half-life, these

380 Brihaye,Butler,Knappatal The Journal of Nuclear Medicine

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generators could be available at a reasonable cost with ashelf-life of 2—3wk if the problems of increasing ‘910sbreakthrough and rapidly decreasing I9ImIr yieldscould be overcome. Recently, we evaluated 39 exchangers and carbon was the most promising (16—18).Thegoals of the present studies were to evaluate carbonabsorbent systems in more detail and to develop a newcarbon-based generator to achieve higher yields ofI9ImIr and lower ‘910sbreakthrough over a period ofseveral weeks without the necessity of a second 19105“scavenger―column.

MATERIALS AND METHODS

Osmium-191 Production and ProcessingOsmium-191 was prepared by neutron irradiation of

isotopically enriched (97.8%) granulated metallic osmium in the Oak Ridge National Laboratory HighFlux Isotope Reactor (HFIR) with subsequent fusionin a mixture of KOH-KNO3 (9). The effects of irradiation period on the levels of 19105, l9ImIr, ‘91Ir,‘92Ir,18505 have been discussed in detail in an earlier study

(19). The production of ‘910sis experimentally linearfor 6 days of irradiation before production yields dcviate from proportionality with time. For routine production, a 3-day irradiation period at a flux of―.-2.5X 10@@n/cm2 . sec compromises between yields of 19105andthe increased formation of undesirable radionuclideimpurities. Under these experimental conditions, theproduction yields per mg ofenriched 97.8% ‘@°0sare asfollows: ‘9'Os,248 mCi; ‘930s,5 mCi; ‘92Ir,0.4 mCi;and ‘94Ir,0.4 mCi. The critical radiochemical impurityis ‘92Irsince 19305 and ‘94Irrapidly eliminate by decay.The presence of ‘921rin the eluate from 1910s/I9lmIrgenerators has recently been discussed (20,21). Afterfusion, the irradiated target is dissolved in water to givean ‘@-‘0.4N KOH solution of potassium perosmate(VIII), K2[0s04(OH)2] (Fig. 1), which is mixed withtwo volumes of ethanol to reduce the Os(VIII) toOs(VI). After 10 mm, five volumes of concentratedhydrochloric acid are added quickly, and the solution isheated in a boiling water bath for 30 mm. The solutionis then evaporated to dryness, and the brick-red precipitate of K2OsC16dissolved in 0.9% NaCl-0.01 N HC1.The kinetics of potassium tetrachloroosmate(VI) reduction in concentrated HC1 during heating with alcohol can be followed spectrophotometrically. The 370nm absorbance corresponding to the maximum of apeak characteristic of K2OsCl6 (22,23) reaches itsmaximal value after 15 mm and remains constant up to5 hr. The use of an 191Ø@solution of perosmate demonstrated quantitative conversion to K2OsCl6. No loss isdetected during the evaporation step, confirming theresults obtained by other authors (24) concerning theevaporation HC1 solutions of K2OsCl6 of different

concentrations.

KOHOs —w-K2[0s04(OH)2](Os—VIll)

KNO3

KOH EtOH

K2[0s02(OH)4] (Os—VI)

HCI

381Volume 27 •Number 3 •March 1986

EXCESS EtOH

K2OsCi6 (Os—lV)

FIGURE1Preparation of K2OsCl6(Os-lV)

Preparation of Activated CarbonAdsorbentEarlier studies suggested that activated carbon was a

good candidate for evaluation as an exchanger for the1910s/l9ImIr system (16—18).A variety of sourcesofcarbon were evaluated. The carbons were pulverized ina mortar and pestle and sieved through U.S. standardsieves.* The 140-230 mesh fraction was chosen forevaluation since it represented a compromise betweensufficient surface area for good 19105binding and rapidI9ImIr release, and a pressure that did not interfere withrapid (@1 sec) elution. For our new prototype generator, 140-230 mesh “activatedcarbon,―twas heated for4-6 hr at 800—900°Cunder a stream of argon whicheffectively removed large amounts of K! and 12 anddestroyed the oxygen surface functional groups.

Comparisonof Elution Characteristics of VariousActivated Carbons

Seven commercially available activated carbon products of different sources were evaluated as potentialadsorbents for the l9lOs/l9lmIr generator system. Thecarbons (140-230 mesh) were slurried in distilled waterand loaded into 1 ml syringest plugged with glass wool.Ten millicuries of a solution of freshly preparedK2OsC16was loaded on each column by means of apump at a flow-rate of 1ml/hr. The columns were thenwashed with 20 ml of pH 2-0.9% NaC1 solution at 3ml/hr. The choice of the nature of the eluting solutionhas been described in a previous study (16). Samples ofthe fixation and wash solution were counted to determine 19105 fixation and ‘921relution percentage. Thecolumns were washed manually with 50 ml of pH 2-0.9% NaCl and yield and breakthrough then measuredusing a 5-ml bolus (Table 1).

Fabrication and Elution of Prototype GeneratorThe 140-230 mesh heat-treated carbon (0.75 g) was

slurried in distilled water and washed successively untilthe decanted solution was clear. The carbon slurry isadded to a plastic 2-mt syringe and plugged with fine

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‘92IrCarbonSourceOsmium

fixation (%)eluted(%)duringfixationlalmlr*yield(%)1910s breakthrough(% /5ml)DARCO4

X 12Lignite99.636.432.49.3 Xi0@Ll-100Coal(low iron)99.911.54.54.9 XiO@11-85Coal99.811.74.21.3

X10220X 40Lignite99.96.518.83.7 XiO@12X 20L1Lignite (low iron)99.87.123.66.7 X1O@FischerCoconut

Shell99.910.318.86.2 XiO@Barneby

CheneyCoconut99.931.531.42.8 Xi0@.

Each bolus consisted ofa 5 mlvolume.

TABLE ISummary of Properties of Difterant Sources of Carbon as Adsorbents for 1910s/l9lmIrGenerator System

Prior to loading, the column is washed with 20 ml ofpH 2-0.9% NaCl prepared by addition of2O ml of 0.5MHC1 to 980 ml of physiological saline solution. Thegenerator is loaded with the ‘91Os(IV)solution with asyringe pump at a rate of about 0.25 ml/min andwashed with 20 ml of pH 2-0.9% NaCl solution at thesame flow rate. The system is then washed with 50 ml of

glass wool. The top of the carbon bed is covered with afine layer of glass wool and a specially designed Teflon“plunger―that fits snugly into the syringe barrel isinserted. The Teflon plunger has a hole drilled along thelong axis and is fitted at the top with a tubing connector.In this manner, readily available syringes can be usedfor the generator body (Fig. 2).

pH 2 —NacIKI BUFFER

GLASS

MIWPORE ALTER

EXTENSIONTUBE@‘3mIVOLUME

THREE-WAY@NNECTORSFIGURE2

Schematic diagram of fabricationandeluting system for carbon-based prototype generator

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eluting solution of composition pH 2-0.9% NaCl contaming 0.250 g KI/l (0.025%) and is ready for use. Fora typical generator system loaded with 700 mCi of‘910s(IV)(specific activity = 200 mCi/mg), the l9lmlrbolus is eluted with 2.5 ml of eluting solution. Neutralization of the acidic eluent is accomplished by theassembly shown in Fig. 2. A second syringe containing0.4 ml of 0.13M Tris buffer acidified to pH 8.4 withHC1 is emptied simultaneously with the elution syringeresulting in immediate neutralization of the generatoreluent. The bolus is stored in a 3-ml extension tube andis injected as quickly as possible by means of physiological solution contained in the injection syringe. In thesystem illustrated, commercial two-way connectors(XKEM-OOl -04) have been used.1 Readily availableintravenous extension tubing and arterial pressure tubing are used with this system. For shielding, standardORNL 2-in. lead shipping pigs have been modified asshown in Fig. 2 to allow use of the pig as the shieldedcontainer. In this way the shipping pig can be used forshielding after receipt, and transfer of the generatorcolumn to a second shielded container is not necessary.The extension tubing is simply attached to the shortlengths of tubing which are capped with Luer dead-endcaps during shipment. A study ofthe automation of thissystem is underway.

Yield and Breakthrough MeasurementBecause of the very short 4.96-sec half-life of l9lmIr,

special techniques described previously (25) must beused for determination of l9lmIr yield. After elution ofthe generator, the l9lmIr must be allowed to decaysufficiently to overcome large gross count loss resultingfrom the detector deadtime. The decay period, denotedas the waiting time, Tw, can be monitored accuratelywith a stop watch. Alternatively, one can use a digitaltimer to actuate the counting system after Tw sec. Theuse of a digital timer is very convenient, since Tw canvary depending on the levels of l9ImIr eluted. Afterwaiting Tw sec, the eluate is counted with a NaI(T1)detector connected to a multi-channel analyzer underdefined geometric conditions. Samples are counted forT@5cc, where T@corresponds to at least eight times thehalf-life of the daughter nuclide (i.e., 40 sec). Theenergy and the intensity of the measured gamma-raywere 129.4 keV and 0.259, respectively. After the decayof the l9lmIr, the samples are counted again for T@secto determine the contribution of the ‘910sto the number ofcounts previously measured (breakthrough). Thelevels of ‘92Ireluted in the bolus are also determined atthis time.

The l9lmIr activity, A (l9lmlr), in iCi at the end ofthe bolus elution was calculated by the relationship:

(1)

where A (l9lmIr) l9lmIr activity in the sample atthe end of elution (sCi);

N (191m Ir) gross number of counts of I9lmIr

measured for TC sec,N (19105) = net number of counts measured

for Tc sec for ‘91Osafterdecay of eluted 191mIr;

A = decay constant of 191mIr (sec');E efficiency of the counter at

the energy of measurement underthe defined geometricalconditions;

“1= intensity of the gamma-raymeasured; and

T@= waiting time before counting (sec).

The elution yield, Y(%), is given by the simple relationship:

Y(%) = A (191mIr) X 100 (2)

A('910s)

where A (‘@‘Os)is the ‘910sactivity in iCi on thecolumn. The 19105activity in the samples is determinedin the usual way and the 19105breakthrough is formulated as the ratio of the ‘@‘Osactivity in the eluatesolution to the 191@activity on the column.

To measure the elution yield of a generator continuously eluted at a flow rate of, f (ml/min), 1 ml issampled after the passage of the equilibrium activitybolus for l's sec (l's 60/f) and counted in the samemanner as for bolus. The l9ImIractivity is calculated byEq. (1). The elution yield is then given by the followingequation:

A (191mIr) X 100Y(%) —A (191Os)X (1—e_XT5) (3)

ABSORBED DOSE ESTIMATES

Detailed distribution studies performed in female

Fisher rats were used as the basis for the dose estimates.Animals were killed at various time intervals up to 8days, with four time points in the first day. Elevenorgans were studied, plus blood, urine, and feces. Theanimal % kg injected activity per g values were converted to % injected activity per organ values in the human.Values for total excretion were assumed to apply directly to humans. Values were analyzed using either linearor nonlinear least squares techniques to fit the retentiondata to either one- or two-compartment exponentialretention functions, respectively. A one-compartmentexponential ingrowth function was included in somecases. Organ residence times were calculated fromthese functions, and dose estimates were generated using the MIRD technique (26). The dynamic urinarybladder of Cloutier et al. (27) was used for activity

[N(l9lmIr N('910s)]xXA (l9lmlr) —xi,,€X'yX3.7X lO4Xe

383Volume27 •Number3 •March1986

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60

@ 50

-J@ 40

>-

z0i: 30D-I

E 20

0'

I@;@

0

6EIn

5,@

4@

x0

3D0II-.

2@La

0'

In00

FIGURE3l9lmlr and 19105 breakthrough as function of KI concentra

tion

clearing through the urinary pathway. The 01 tractmodel described in ICRP 30 (28) was used for materialclearing through the GI. The excess cumulated activity

correction (29) was used for activity in the remainder ofthe body.

RESULTS

The goal ofthe present study was to further evaluate themerits ofactivated carbon as an adsorbent for a newI9lmIr generator system. Osmium-191 in the form ofhexachloroosmate (K2OsC16, Os-IV) is more stablethan Os(VIII), Os(VI) or Os(III) and was used to loadthe generators. The I9ImIr yield and l9lOs breakthrough, determined as described earlier (16—18),wereevaluated using several sources of activated carbon(lignite, coconut, wood, etc.). The results of thesescreening studies are summarized in Table 1. Sevendifferent commercial carbon products were evaluatedunder the same conditions. These results suggested thatBarneby-Cheney carbon was the best candidate forfurther study. Both yield and breakthrough varied in anunpredictable manner using carbon from differentsources. Since the properties of the carbon productsvaried so much, the possibility that either specific functional group or trace element content was affecting theproperties as a generator was investigated. Since activated carbon is known to contain oxygen-carbon functional groups (-COOH, -CH2OH, -CHO, etc.), groupmodification by room temperature oxidation withHNO3, KMnO4, H2O2, HOC!, etc., was studied. Thesetreatments had little effect. In addition, x-ray fluorescence analysis showed that yield and breakthroughcould not be correlated with trace element content.

Thermal treatment and chemical analysis, however,indicated that the carbons contained varying amountsof K! and 12. Because of proprietary considerations,

manufacturers do not describe the production and activation methods for their carbon products. Thus, thepresenceof large amountsof KI and 12wasunexpectedand was detected by established methods. One source ofcoconut carbon (140-230 mesh) gave reasonablyconsistent results with “-@35—40%yield and ‘—‘1X 10@%/5 ml breakthrough and was used for further study andfor the developmentof the prototype I9IOs/l9lmIrgenerator described below.

The l9ImIr yield and ‘910sbreakthrough were measured with increasing concentrations of KI in the pH 2saline eluent (Fig. 3). These results demonstrate theimportance of the presence of iodide ions in optimizingthe l9Imfrelution yields. Also, the addition ofKI resultsin the elution of l9lmIr as a discrete bolus (Fig. 4).

Presumably, in the presence of iodide ions, hexachioroiridate ions are converted into hexaiodoiridate ionswhich are adsorbed less on activated carbon. Thoseconsiderations incited us to design a prototype generator using heat-treated carbon as adsorbent and elutedwith 2.5 ml of a pH 2-0.9% NaCl solution containing0.25 g KI/l. A typical elution profile is shown in Fig. 4.With a 2.5 ml volume, 85% of the equilibrium bolusactivityis eluted with the activityeffectivelycontainedin 2.0 ml since the activity in the first 0.5 ml can beneglected. The elution characteristics of the prototypegenerator are summarized in Table 2. The l9tmIr elution yieldand the ‘9'Osbreakthrough are independentof the time and a volume of 1,000 ml is allowed to passthrough the generator without altering its properties.

This generator can also be eluted continuously. A lowmean elution yield of 3.7% (range: 1.2 to 5.5% after 2 1of eluent) was measured at a flow rate of 12 ml/minwith a mean ‘9'Osbreakthrough of 2.0 X 105%/ml(range: 1.7 X 10@ to 2.9 X l05%/ml) after 2 1.Due toits short half-life, the I9lmIr grows very rapidly. Conse

40EInaE

a'

@ 200

(3 10E

0

FIGURE4Typical elution profile of prototype l9lOsi@9lmIr generatorsystem (19105activityof 700 mCi)

30

0 1 2 3 4 5VOLUME (ml)

53 106 159 212 265 318 371KI CONCENTRATION (mg/liter)

384 Brihaye,Butler,Knappatal The Journal of Nuclear Medicine

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TABLE 3Estimates of Absorbed Doses from l9lmlr,l9lØ@

par Injected 2 ml Bolus (100 mCi lolmIr).and192lrmrad

per 2 mlinjectionFromlelmIr From 1910s From192lrTotalOrgan

(mrad) (mrad) (mrad)(mrad)

TABLE2ElutionCharacteristics of Prototype l9lØ@/l9lmlrGeneratorNo.7 Prepared from Thermal-Treated 140-230MeshBarneby-Cheney

Carbon Loadedwith ‘910S(IV)Values

per 2 mlbolusTotal'Elapsed@OsBolus

volume (ml) time lelmIr breakthrough192lrno.eluted (days) Yield (%) (%/2 ml)(@iCi)1

50 0 18 2.9X1040.750175 1 17 2.5 X i0@0.580250 3 19 2.3X i0@0.4110325 8 18 2.3X1040.3150475 15 19 1.6X iO@0.2280750 20 21 1.7X iO@0.2380

1,000 22 22 1.8X iO@'0.3‘

Each bolus consisted of a 2 mlvolume eluted inapproximately1

sec.

Bladder—2.72.65.3Brain0.090.060.30.4Small

intestine14.01.02.017.0Heartwalls0.60.41.22.2Kidneys2.54.04.911.5Liver1.45.71.88.9Lungs0.80.41.32.5Ovaries1.40.82.24.4Redmarrow1.50.92.04.5Spleen0.83.45.69.7Testes1.00.71.93.6Thyroid2.42.23.98.4

Totalbody 1.2 0.9 1.8 3.9

* 800 mCi 191@ generator; 1910s breakthrough 2. 1 X 1O@% I

bolus; 192lractivity0.35 zCi/bolus.

adverse effects detected in normal male volunteers afteradministration of 2.5 ml bolus injection using the system shown in Fig. 2. No radiolysishas been detectedeven after 3 wk for generators loaded with up to 1 Ci of19105 Since the volumes of the eluent and buffer solu

tion can be reduced proportionately, it should be possible to use this system for shunt evaluation in childrenwhich requires a small bolus of <1 ml. As an example,we have eluted this system with 1 ml of eluent simultaneously buffered with 0.16 ml of Tris buffer, with anelution yield of 10%I9lmIr.Since ‘@-20mCi of l9lmlr areusually used for radionuclide angiography of shunts inchildren (10), a 250 mCi generator would be expectedto yield 25 mCi of l9lmIr, more than sufficient for thismeasurement. In adults, I9ImIrhas been useful for theevaluation of left ventricular ejection fraction (LVEF)after administration of up to 100 mCi of l9lmIr (13).

The radiation dosimetry values based on biodistribution in rats for eluates of our new prototype generatorhave been calculated, since the use of activated carbonwith osmium in oxidation state (IV) are parameterswhich have not been previously studied. The absorbeddose estimates for several organs resulting from theinjection of a 100 mCi l9lmIr bolus are summarized inTable 3. The contributions of t9lmIr, l9lOs, and ‘92Irareincluded.

FOOTNOTES

* W.S. Tyler Company, Mentor, Cleveland, OH.

t Barneby Cheney, Columbus, OH.

I Becton—Dickinson,Rutherford, NJ.§Millipore Corporation, Bedford, MA.

quently, even for such a low elution yield, the elutionrate of l9lmIr is as high as 1.3 mCi/sec at 12 ml/min fora 250 mCi ‘910sgenerator, which results in the injectionof 6.5 mCi of l9lmlrper injectedml.Thisactivityissufficient for many medical applications requiring continuous infusion. For the study described above, themeasured ‘92Iractivity was 0.020 j.tCi/ml. A volume of2 1 can pass through the generator before the 19105

breakthrough increases to 5 X l05%/ml.

DISCUSSION

The goal of the present studies was to develop a new‘910s/l9lmIr radionuclide generator system whichwould provide l9lmIr in consistently good yield with low19105 breakthrough. We have found that activated car

hon is an excellent generator adsorbent and retainsthese properties for 2—3wk. Consistently high yields ofl9lmlr are obtained over a prolonged period with multiplc elutions, and breakthrough remains constant duringthis period. This simple generator design also does notrequire a scavengercolumn.The eluent is neutralizedwith a Tris buffer to give an isotonic solution at physiological pH ready for direct intravenous injection. Theadsorption of ions on activated carbon has been described in many papers (30—32)where investigatorshave noted that osmium is adsorbed on activated carbon while iridium is not retained in 0.01 N NH4C1 andin 0.01 N HC1 solutions (30).

In the present work, >99.9% of the (‘@‘Os)K2OsCI6is bound to the activated carbon during the loading andwashing procedures. Yields of 16-20% can be obtainedin a 2.5 ml bolus elution volume. The void volume of a200-400 mCi generator is 0.7-0.9 ml. The use of anautomated system should allow the void volume to bediscarded, making a smaller bolus of activity availablefor pediatric applications (33,34). Six prototype generators ofthis type have been used in clinical trials with no

VoIume27 •Number3 •March1986 385

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15. Packard AB, Treves 5, O'Brien GM, et al: Chemicaland physical parameters affecting the performance ofthe Os-l91 /Ir-191 m generator. In Radionuclide Generators: New Systems for Nuclear Medicine Applications, Butler TA, Knapp FF, Jr., eds. ACS SymposiumSeries 241, Washington, DC, ACS, 1984, pp 51-66

16. Brihaye C, Butler TA, Knapp FF, Jr.: The Os-19l/Irl9lm generator for clinical use. I. Evaluation of potential adsorbents. J Radioanal and Nucl C/tern: in press,1984

I 7. Brihaye C, Butler TA, Knapp FF, Jr.: Evaluation ofadsorbents for the osmium-19l/iridium-191m ultrashort-lived radionuclide generator system. In Fifth International Symposium on RadiopharmaceuticalChemistry, Tokyo, Japan, July 9-1 3, J Labl CompdsRadiopharm 21:1045-1047,1984

18. Brihaye C, Butler TA, Knapp FF, Jr.: Evaluation ofpotential adsorbents for the 1910s/l9lmIrradionuclidegenerator system. J Nucl Med 25:1 18, 1984 (abstr)

19. Butler TA, Guyer CE, Knapp FF, Jr.: Nuclear Medicine and Biology Advances, Vol. 1, Raynaud C, ed.Paris, Pergamon Press, 1983, p 617

20. Hetherington ELR, Sorby PJ: The presence of ‘921rinthe eluate from I9lOsJ9lmIr generators. Int J App!Radiat Isot 35:68, 1984

21 . Packard AB, O'Brien GM, Treves 5: ‘92Irconcentrationin the eluate of the t9tOs_t9lmIr generator. In: J App!Radiat Isot 36:164, 1985

22. Larson LL, Garner CS: Non-exchangeof chlorine between chloride and hexachloroosmate(IV) ions in aqueous solution. J Am Chem Soc 76:2180-2181, 1954

23. Miano RR, Garner CS: Kinetics ofaquation of hexachloroosmate(IV) and chloride anation of aquapentachloroosmate(IV) anions. Inorg Chem 4:337—342, 1965

24. Faye GH: Behavior of osmium during evaporation ofhydrochloric acid solutions of chloroosmate. AnalChem 37:296-297,1965

25. Guillaume M, Brihaye C: The short-lived radionuclidegenerator. Physical characteristics, assessment and conditions for optimal clinical use. In Radionuclide Generators: New Systems for Nuclear Medicine Applications, Knapp FF, Jr., Butler TA, eds. ACS SymposiumSeries 241, Washington, DC, ACS, 1984, pp 185—197

26. Loevinger R, Berman M: A revised schema for calculating the absorbed dose from biologically distributed radionuclides. MIRD Pamphlet No. 1, Revised. NewYork, The Society of Nuclear Medicine, 1976

27. Cloutier R, Smith 5, Watson E, et al: Dose to the fetusfrom radionuclides in the bladder. Health Phys25:147-161,1973

28. Committee 2 of the International Commission on Radiological Protection. ICRP Publication 30, Part 1:Limits for the Intakes of Radionuclides by Workers,New York, Pergamon Press, 1978

29. Cloutier R, Watson E, Rohrer R, et al: Calculating theradiationdosetoanorgan.JNucl Med 14:53—55,1973

30. Akatsu E, Ono R, Tsukeuchi K, et al: Radiochemicalstudy of adsorption behavior of inorganic ions on zyrconium phosphate, silica gel and charcoal. J NucI SciTechnol2:l4l—l48,1965

31 . Nelson F, Phillips HO, Kraus KA: Absorption of inorganic materials on activated carbons. Proceedings of29th Industrial Waste Conference, Purdue University,1974,pp 1076-1090

32. Huang CP: Chemical interactions between inorganicsand activated carbon. In Carbon Adsorption Handbook, Cheremisinoff PN, Ellerbusch F, eds. Ann Arbor,

386 Brihaye,Butler,Knappatal The Journal of Nuclear Medicine

ACKNOWLEDGMENTS

This work was sponsored by the Office of Health andEnvironmental Research, U.S. Department of Energy, undercontract DE-ACO5-840R21400 with Martin Marietta Energy Systems, Inc. C. Brihaye, Charge de Recherches duFNRS, thanks le Fonds National de la Recherche Scientifique (Belgium) for allowing him to work at the Oak RidgeNational Laboratory in 1983.

REFERENCES

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2. Knapp FF, Jr., ButlerTA, eds: In Radionuclide Generators: New Systems for Nuclear Medicine Applications. Washington, DC, ACS, 1984

3. Campbell EC, Nelson F: Rapid ion-exchange techniques for radiochemical separations. J Inorg NuciChem 3:233-242,1956

4. Yano Y, Anger HO: Ultrashort-lived radioisotopes forvisualizing blood vessels and organs. J Nucl Med 9:2—6,I968

5. Yano Y: Radionuclidegenerators: Current and futureapplications in nuclear medicine. In Radiopharmaceuticals, Subramanian G, Rhodes BA, Cooper JF, eds.New York, The Society of Nuclear Medicine, 1975, pp236-245

6. Hnatowich Di, Kulprathipanja 5, Treves S: An improved l9lOs@I9lmIr generator for radionuclide angiocardiography. Radiology 123:189-194, 1977

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387Volume 27 •Number 3 •March 1986

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1986;27:380-387.J Nucl Med.   C. Brihaye, T. A. Butler, F. F. Knapp, Jr., M. Guillaume, E. E. Watson and M. G. Stabin  CarbonA New Osmium-191/Iridium-191m Radionuclide Generator System Using Activated

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