Institut für Bioanorganische und Radiopharmazeutische Chemie

1. * average values PTFE – tube PP – tube PTFE – tube PP – tube Institut für Bioanorganische und Radiopharmazeutische Chemie FACTORS AFFECTING THE SPECIFIC ACTIVITY OF [18F]FLUORIDE FROM A WATER TARGET F. Füchtner, S. Preusche, P. Mäding, J. Steinbach * * Institut für Interdisziplinäre Isotopenforschung, Permoserstraße 15, 04318 Leipzig, Germany AIMS: The nuclear reaction 18O(p,n)18F is the method of choice for routine production of n.c.a. [18F]fluoride to synthesize labeled compounds on high activity level as well as with high specific activity (SA). For quite a few PET radiopharmaceuticals the SA has to be high in order to prevent physiological response of the studied system. We found that the SA shows considerable variation, as also reported in the literature [1-6]. The SA is an important quality parameter in accordance with the GMP guidelines and should be reproducible. The SA of the radiopharmaceuticals mainly depends on the SA of the [18F]fluoride dispensed from the cyclotron target system after irradiation. Initial investigations indicated that the main origin of 19F is the [18O]water dispensing and delivery system of the target and not the starting [18O]water itself. Detailed ion chromatographic investigations were carried out to determine the contamination sources of the 19F. • Background: starting assumption • SA - limit of SA for radiopharmaceuticals ready for use 40 GBq/µmol (~ 1 Ci/µmol) • - time between EOB and injection = 2.5 h • ╚> SA(EOB) = 103 GBq/µmol • Activity - 400 MBq injection activity • - 10 % reaction yield • - 80 % of the finale product volume will be injected • ╚> required minimum starting activity EOB: 13 GBq with 126.2 nmol 18F and 19F • - target water contains 0.2 nmol 18F (0.003 ppm) • - and may contain 126 nmol 19F (2.14 ppm) METHODS: [18O]water and [18F]/[18O]water samples from different places of the target dispensing and delivery system were analyzed for [19F]fluoride using ion chromatography. The SA of the labeled receptor ligand [18F]ZK811460 [7] (n=52) was determined by RP chromatography using a UV detection. • Target water dispensing and delivery system, IBA CYCLONE 18/9 (modified system) • * - PTFE tube was replaced by PP tube • A - J: measuring points, determination of [19F]fluoride The average value and its standard deviation of the cold amount | SA of the [18F]ZK811460 using PP tubes (n=30) in the target dispensing system in contrast to PTFE tubes (n=22) could improved from 6632 nmol | 5635 GBq/µmol (PTFE) to 3816 nmol | 12035 GBq/µmol (PP). On the other hand: In our experience PTFE tubes of the target water delivery system have the best transport properties related to the [18F]/[18O]water bolus. In general, its contribution to the [19F]fluoride amount (contamination up to 20 nmol/300 ppb) is minor. If very high SA is required repeated rinsing of the whole delivery system with ultra pure water becomes necessary instead of changing the whole PTFE tubing system by PP. RESULTS:The starting [18O]water is of good quality and contains no significant amounts of [19F]fluoride (0.5 nmol/8 ppb). A considerable contribution of the target irradiation process to the [19F]fluoride amount was not found. The [19F]fluoride amount of the dispensing system mainly depends on the tubing materials and the radiation dose, which is exposed to the tube near the target/cyclotron (the water/tube contact time). The PTFE tube of the dispensing system is the main origin of [19F]fluoride (contamination up to 380 nmol/5550 ppb). Avoiding PTFE tubes and changing to PP (polypropylene) tubes the [19F]fluoride amount can be decreased considerably (maximum contamination 10 nmol/170 ppb). [18F]ZK811460 specific activity [GBq/µmol] [19F]fluoride concentration [ppm] limit value for medicinal application = 40 GBq/µmol [18F]ZK811460 amount [nmol] [19F]fluoride concentration of [18O]H2O water in dependence of the tube material, water/tube contact time (radiation dose) and the place in the tube (the first fraction is the nearest to the target; fraction volume = target volume = 1.3 ml ) Tracer amount and the corresponding specific activity of [18F]ZK811460 in dependence on tube material of the target dispensing system REFERENCES: [1] Dence C. et al., proceedings WTTC 6, Vancouver, 1995; 199-205 [2] Kilbourn M.R. et al., Int. J. Appl. Radiat. Isot. 1984; 35: 599-602 [3] Nishijima K. et al., Appl. Radiat. Isot. 2002; 57: 443-449 [4] Schlyer D.J. et al., Appl. Radiat. Isot. 1993; 44: 1459-1465 [5] Shiue C.Y. et al., J Nucl Med 1985; 26: 181-186 [6] Solin O. et al., Appl. Radiat. Isot. 1988; 39: 1065-1071 [7] Maeding P. et al., Annual Report 2002; FZR-363: 40 and 2003; FZR-394: 31; ISSN 1437-322X CONCLUSION: By replacing PTFE tubes by PP tubes of the water target dispensing system the contamination of [18F]/[18O]water with [19F]fluoride can be reduced by the factor of at least two. member of Leibniz-Gemeinschaftwww.fz-rossendorf.de Corresponding author: Dr. F. Füchtner Tel. +49 351 260 2804 FZ Rossendorf f.fuechtner@fz-rossendorf.de Postfach 51 01 19 D-01314 Dresden WTTC 10, Madison, Wisconsin, August 13-15, 2004