Impact of Target-Gas Purity on F-18 Form in 18F-F2 Production with Neon/Fluorine Target, Study notes of Nuclear medicine

Download Impact of Target-Gas Purity on F-18 Form in 18F-F2 Production with Neon/Fluorine Target and more Study notes Nuclear medicine in PDF only on Docsity! The production of ‘8F-F2of high specific activity using the @°Ne(d,a)'8Freaction has been of considerable interest in light ofits use in the synthesis of 2-['8F] flu oro-2-deoxy-D-glucose Q8FDG), a tracer that has been used successfully in the quantitative measurement of regionalbrainglucosemetabolism(1). Moreover,itsuse in clinicalresearchrequiresa highlyreliableproduction method. We have recently described a simplified system for ‘8F-F2production that eliminates the need for a high vacuum system and the handling of pure fluorine gas (2). This system, although manually operated, eliminated problems of direct handling of radioactive targets and allowed for the development of a remotely operated synthetic method for ‘8FDG(3). A major factor in the simplificationof thissystemwastheuseof a commer cially available mixture of 1%fluorine in neon,which was subsequently mixed with research-grade neon to ReceivedNov. 26, 1979;revisionacceptedFeb.22, 1980. For reprintscontact:Alfred P. Wolf, PhD, Dept.of Chemistry, BrookhavenNatjonal Laboratory, Upton, NY I 1973. provide a target gas with the required amount of carrier ‘9F2.The target, which typically contained 0.1% F2 (‘—-‘ 60 zmol), and this ‘8F-F2production system have been used routinely for over a year with no difficulty to pro duce ‘8FDGfor human neurological studies. Recently, however, the production of F- 18 as ‘8F-F2 decreased rapidly with a concomitant dramatic increase in the production of F-l8-labeled, chemically inert gaseous material(s)*. The serious consequences of this problem to the reliability of the production of ‘8F-F2and of labeled compounds requiring its use, necessitated an investigation of the factors influencing the chemical form of F-18 produced from the 20Ne(d,a)'8F reaction in the presence of carrier F2. Additionally, it was felt that er ratic behaviorof this target systemreportedby other laboratories reinforced the needfor a thorough investi gationof itscauses.The factorsneedingto beidentified and reported on in this paper include: (a) assay of target gases for contaminants that react with F2, resulting in the production of large quantities of chemically inert F-18-labeledproductsat the expenseof ‘8F-F2;@(b)de scription of the analytical methods for assaying target 758 THE JOURNAL OF NUCLEAR MEDICINE TheEffectof Target-GasPurityontheChemicalFormof F-18during18F-F2 ProductionUsingthe Neon/FluorineTarget Gerald T. Bide, Richard L. Ehrenkaufer, Alfred P. Wolf, Joanna S. Fowler, Robert R. MacGregor, and Thomas J. Ruth Brookhaven NatlonalLaboratory, Upton, New York Irradiation of gas mixtures of F2/Ne (@°Ned.@18F)which containedpercent levels (>0.1 % ) of N2,C02, or CF4resultedIn the productionof unacceptable1ev ciaof F@18-labeledNF3andCF4at theexpenseof 18F-F2.Analyticalgaschromato graphicmethodshavebeendevisedto determIflecontaminantlevelsin the target gas as well as in the productsarisingfrom them. Commercialmixturesof I % f2/ Na,pureF2,andneonhavebeenanalyzedfor contaminants(N2,02,CO,C02,and CF4) andfoundto vary widely In the levelsof these Impuritiesfrombatchto batch. TheN2levóisin the I % F2/NemixturesvarIedfrom 0.039to 0.49%, andthe CO2 levelefrom 0.028 to 0.13%. No detectable impurities were found In the neon (Re search Purity), but F2 was found to contain “11% CF4. Reproducibly high yields of 18F-F2are obtainedif the levelsof N2,C02, and CF4In the final target gas mix turfare<0.01% andcarrierF2is‘@‘0.1%. HydrocarbonsandCOWerenotdetect ed In our gas mixtures, but would also be expected to decrease yields of ‘F-F2. ,I Nucl Med 21: 758—762,1980 determined determined sh. 0.028 none detected 0.22 none detected none 0.24 0.12 Source(dateSampleGas received)designation % N2 % 02 % CO2 % CF4 0.60 BASIC SCIENCES RADIOCHEMISTRYAND RADIOPHARMACEUTICALS gas mixtures; (c) the identification and quantitation of the inert F-I 8-labeled products from the Ne/F2 target; and (d) conditions and specifications for a reproducible and effective gaseous target composition for ‘8F-F2 production. MATERIALS AND METHODS Irradiation conditions, targetry, and gas handling system.All irradiations wereperformed at the BNL 60-in. (I.5-m) cyclotron. TheInconel600two-portargetandflow-throughloadingsystem describedpreviously were used(2). The 23-MeV deuteron beam from the cyclotron wasdegradedto 14.0MeV beforeentering the target gas.Sufficient target gas(“—25atm) is usedto degradethe beambelowthresholdunlessotherwiseindicated.Irradiations were carriedoutat constantdoseanddoserate—namely,10 @iAfor 10 mm (theoretical F-l8 yield: 50 mCi) (4)—with typical F-18 re coveriesbeing 40-50%of the theoretical value. Although the In conel target wasusedin thesestudiesasa matter of convenience, production targets must havehighly polishedpure nickel surfaces whereverexposedto the F2/Ne mixture (2). The contentsof the target after irradiationwereanalyzedby purging them through a seriesof traps containing KI, sodalime, and charcoal as previously described (2), with modifications to accommodate various sampling vesselsas described in the fol lowing section. Although one can postulate other fluorine-con taming compounds that would be hydrolyzed in water or would oxidize KI, we support our identification of the predominant chemical form recovered from the target as F2 by its chemical reactivity with 3,4,6-tri-O-acetyl-D-glucal to producethe difluoro adducts (5). Work is in progressto developnew analytical tech niques for F2and the minor reactive gaseousproducts. Target gases. FLOURINE IS A HIGHLY TOXIC AND REACTIVEGAS.THEREADERISDIRECTEDTOASE RIESOFARTICLES(6,7)ONTHEMANIPULATIONAND HANDLING OF GASEOUS FLUORINE IN ORDER TO BECOME FULLY AWARE OF THE HAZARDS IN HAN DLING THIS DANGEROUS GAS. The variouscommercialF2/Ne mixturesare identified for referencein Table 1. Undiluted F2 (3.4 atm)t andundilutedNe (ResearchGrade)t were alsoobtained commercially. Target-gas analyses.Gas chromatographic analysis of target gases(before and after irradiation) was usedto identify and quantitate N2, 02, CO, CO2. CH4, and CF4 contaminants. Sam piesof targetgaswereanalyzeddirectlyfrom the target,aswell asafter removal of fluorine, to ensureagainst the introduction of artifacts due to the possiblereactivityof the fluorine with the columnmaterials.Analyseswereperformedusingan analyzer1 equipped with a thermal-conductivity detector and digital pro cessorto quantitatemasspeakareas.Samplesof the target gas werecollectedin flow-throughgasbulbsfitted with Burrellseals for purposesof analytical screening.Sampleswere withdrawn in gaslight syringesand injected onto the column. Conditions were asfollows (contaminant gas,column characteristics,temperature, He flow rate, retentiontime): for oxygen,molecularsieve5A (60—80mesh),6 ft X 1/@in., 50°,21cc/mm, 3.0 mm; for nitrogen, molecular sieve,50°,21 cc/mm, 5.7 mm; for carbon monoxide, molecularsieve,50°,50 cc/mm, 9.4 mm; for carbondioxide, silica gel (30—60mesh),6 ft X ‘/@in., 75°,31cc/mm, 10.6mm;andfor carbontetrafluoride,silicagel, 35°,21 cc/mm, 6.6 mm. Whenabsolutevalueswererequiredandwhentheexclusionof air from the sample was necessary,gaseswere collected in cali bratedglasssamplingloops.The loopswereattachedon-lineto the column, the dead-volumegassweptout, and the samplepassed Sh.t1% F2/Ne Matheson(12/77) (A) 0.040 0.068 none detected not1% F2/Ne Matheson(4/78) (B) 0.046 sh. not 1 % F2/Ne Matheson (8/79) (C) 0.039 2% F2/Ne Homemade 1% F2/Ne@ Homemade'1 (D) (E) 0.006 0.003 0.16 none detected 0.131% F2/Ne@ Matheson(1/79) (F) 0.49 detected nonedetected none 11.0•• Neon1 Matheson (G) none detected none detected not none detected notF2 AirProducts (H) not•@ determined determined determined . 1 % F2/Ne mixtures were purchased in size 3F gas tanks at a pressure of 35 atm. t Appeared as a shoulder on the neon peak and was too small to be integrated. @ These “homemade―mixtures were prepared using Air ProductsF2(TankH)and MathesonResearchPurity neon (TankG). IIInthepreparationofTankE,thefluorinewaspassedthrot4@a liquid-N2traptoremoveCF4andCO2. SAll premixed gaseswere preparedwith ResearchPurftyneonexcept Tank F, which was inadvertentlysupplied with purified neon. I Research Purity neon. . . Not directly determined but can be estimated from analysis of D or E. Volume 21, Number 8 759 TABLE1. IDENTIFICATION,SOURCE,AND PURITYANALYSISOF TARGETGASES