A windowless 13N production target for use with low energy deuteron accelerators

Pergamon

.

I

NW/. Med. BioI. Vol. 21, No. 7, pp. 977-986, 1994 Copyright 0 1994 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0969~8051/94-$7.00 + 0.00

A Windowless 13N Production Target for Use with Low Energy Deuteron Accelerators R. E. SHEFER’*t,

B. J. HUGHEY’,

R. E. KLINKOWSTEIN’t,

M. J. WELCH’

and C. S. DENCE* ‘Science Research Laboratory, Inc., 15 Ward Street, Somerville, MA 02143, U.S.A. and 2The Edward Mallinckrodt Institute of Radiology, Washington University Medical School, 510 South Kingshighway Blvd., St Louis, MO 63110, U.S.A. (Accepted 4 December 1993) The recent development of low energy accelerators for positron emission tomography has necessitated the development of new targets for 13N production. “C(d ,n)t3N reaction yields in graphite at low deuteron beam energies (0.8-3.2 MeV) are presented and a new technique for the in situ extraction of t3N activity from solid graphite and subsequent conversion to [“N] ammonia is described. The target is windowless and is reusable for multiple isotope production runs. This technique utilizes radio frequency induction heating to rapidly heat the graphite to combustion temperatures in an 0, gas stream. The conversion of activity induced in the target to [“N] ammonia in under 10 min with an overall decay-corrected efficiency of 45% is reported.

Introduction One of the most important

clinical applications

of

PET is as an accurate means of identifying viable myocardium. The most commonly used positronemitting agent to study myocardial blood flow is 13N-ammonia (Beanlands et al., 1992; Bellina er al., 1990; Choi et al., 1993; Delbeke et al., 1992; Hutchins et al., 1990; Khanna et al., 1992; Krivokopich et al., 1982; Muzik et al., 1993a; Muzik et al., 1993b; Schelbert et al., 1982 & 1981; Shah et al., 1985; Tamaki et al., 1988; Yonekura et al., 1987). Labeled

ammonia has been used to accurately quantitate myocardial blood flow (Shah et al., 1985; Bellina et al., 1990; Hutchins et al., 1990; Muzik et al., 1993a, b; Choi et al., 1993) and 13N-ammonia myocardial PET with exercise loading has been shown to provide high quality tomographic images of regional myocardial perfusion and to be a valuable technique for detecting coronary artery disease (Yonekura et al., 1987; Khanna et al., 1992; Delbeke et al., 1992). ‘3N-ammonia can also be used in conjunction with ‘*F to identify viable myocardium by examining the enhanced uptake of ‘*F-fluorodeoxyglucose (FDG) in relation to myocardial blood flow (Tillisch et al., 1986). In *Author for correspondence. tCurrent address: Newton Scientific Inc., 7 Red Coach Lane, Winchester, MA 01890, U.S.A.

addition, 13N-ammonia has been used to study blood flow in the brain (Raichle and Larson, 1981). liver (Chen et al., 199la), kidney (Chen et al., 1991b), and malignant tumours (Schelstraete et al., 1985). The recent development of compact, low-energy (less than 4 MeV) accelerators for the production of PET radioisotopes (Shefer et al., 1992; Clark and Morelle, 1992; Hagan et al., 1992) has led to renewed interest in the development of targetry for low energy beams (see accompanying paper, Dence et al., 1994). The ‘2C(d,n)‘3N nuclear reaction has a low threshold energy (0.33 MeV) and a high yield at low bombarding energy. A charcoal slurry target using this reaction has been investigated for use with 3.5 MeV deuteron beam (Morelle and Lienard, 1992). However, the requirement for a foil target window with any liquid or gas phase target is particularly disadvantageous at low beam energy because a large fraction of the beam energy will be deposited in the window itself. Carbon12 in the form of solid graphite is an excellent accelerator target material. A solid graphite target can be placed directly in the accelerator vacuum beam line, thereby eliminating the need for a target window. In this paper, we present 13Nyields in solid graphite via the ‘2C(d,n)‘3N nuclear reaction at deuteron bombarding energies of 0.8-3.2 MeV and describe a highly efficient technique for the rapid, in situ extraction and trapping of the 13N activity in a chemical

911

R. E. SHEFER ef al.

978

form suitable for conversion to [“N]NH3. The extraction technique utilizes radio frequency induction heating to heat the graphite target pellet to the temperatures required for combustion in a time period of approx. 1 min. The target pellet remains in the target chamber during heating and combustion and the thickness of graphite combusted is controlled by limiting the quantity of O2 gas introduced into the chamber. Because of the short range of the low energy deuteron beam in graphite, 13N activity is produced close to the target surface and only a thin layer of graphite must be combusted in order to extract the activity. In the experiments described below, we have demonstrated that greater than 99% of the “N activity produced by target irradiation with 1.2-3.2 MeV deuterons can be extracted by controlled combustion of a surface layer of graphite containing the activity, and that the target pellet is reusable for multiple “N production runs. These experiments have also established the compatibility of the solid graphite target with accelerator vacuum requirements under conditions of multiple irradiation and combustion cycles. Thus, the target may be used in a windowless configuration, thereby obviating the problems associated with beam energy loss and window foil heating during low energy irradiation. The 13N production yields and extraction techniques described below, in conjunction with the trapping and chemical synthetic techniques developed for use with this target, will allow the production of clinically useful batches of

13N-ammonia with presently available deuteron accelerators using beam energies down to approx 1 MeV.

Materials and Methods j3N yield measurements

Nitrogen-13 yields from the i2C(d,tQJ3N nuclear reaction were measured by irradiation of solid graphite with 0.8-3.2 MeV deuterons from a tandem cascade accelerator (TCA). The TCA is a 3.7 MeV electrostatic linear accelerator developed at Science Research Laboratory (SRL) for PET radioisotope production (Shefer et al., 1992). In the energy range 0.8-l .4 MeV, 3.2 mm thick graphite disks (AGOT Grade, UCAR Carbon Company) were mounted on an aluminum plate in the accelerator vacuum beamline and irradiated for 10 min at each energy. Experiments were performed at low deuteron current (2 PA) to ensure that no loss of activity occurred due to beam heating of the graphite during irradiation. After each irradiation, the graphite pellet was removed from the vacuum chamber and placed in a radioisotope calibrator (Capintec CRC-12). In addition, yield measurements at 2.4 and 3.2 MeV deuteron energy were performed using the graphite target described in the following subsections. “N target design and bombardment conditions A solid graphite target which can be rapidly heated in situ after irradiation to release 13Nactivity from the graphite matrix was fabricated and tested. A schematic cross-sectional drawing of the target is shown

Ceramic Tube

RF Induction Coil

Water Outlet Gas Inlet

7

Gas Outlet -,

AfsS

Walter Inlet -J

Electrical Feedthrough

L Thermocouple\

Cooling J Jacket 0 I Fig. 1. Windowless

5cm 1

1

1

“N production

1

I

target.

Graphite Target

13N Target

for low energy

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Graphite Target in RF Induction Oven

Gate Valve H/silica Traps to rough pump

to 02/He gas fill Calibrator

Flow Controller Fig. 2. “N production

target

with gas recirculation

Fig. 1. A graphite pellet was mounted inside an evacuated ceramic (Mullite, 2.2cm I.D.) tube surrounded by a water cooled radio-frequency heating coil. After target irradiation, the target chamber was isolated from the accelerator vacuum beamline with a gate valve and a measured quantity of O2 gas was admitted into the chamber. The RF coil was then energized with a 750 W, 30 kHz RF power source. The time varying magnetic fields created by the coil produce eddy currents in the graphite and resistive heating by these currents rapidly elevates the graphite to the temperature at which combustion begins (750°C). In the experiments, the target was maintained at this temperature, or higher, until combustion was complete. The total mass of graphite combusted was controlled by limiting the quantity of oxygen introduced into the target chamber. The target was designed to maximize the coupling of RF power to the graphite during heating while minimizing coupling to the support structure. Efficient coupling to the graphite was achieved by maximizing the fraction of the coil cross-section occupied by the pellet. The target pellet was disc shaped with a threaded stem and was machined from a single piece of graphite. The disc outer diameter was 1.9cm and the thickness was 0.64cm. The pellet stem was threaded onto a thin-walled, water-cooled stainless steel tube assembly to provide some conductive cooling during deuteron beam bombardment. Thermal contact between the graphite and the stainless steel tube was enhanced with a commercial heat transfer agent (Watlube, Watlow Electric Co.). A type K (Chromel-Alumel) thermocouple was inserted into a in

system

for extraction

and trapping

of activity

hole in the back of the target, as shown, to monitor the target temperature during irradiation and combustion. Type K thermocouple wire was chosen because of its relatively high oxidation resistance. Two varieties of graphite were tested: (1) ECL graphite, a high purity, medium grain size graphite with a density of 1.68-1.74 g/cm3, and (2) ZL-3 graphite, an ultra low-porosity graphite with a density of 1.78 g/cm’. Both types of graphite were obtained from UCAR Carbon Company. Some samples of each graphite type were heat-treated at 2000-2200°C in a commercial vacuum furnace prior to deuteron bombardment. The purpose of the heattreatment was to remove absorbed 14N from the graphite lattice (Kohl, 1960). All deuteron bombardment experiments reported below were conducted using the TCA at SRL. The TCA was operated with beam energies in the range 0.8-3.2 MeV and currents of up to 70 PA. The beam diameter on target under all irradiation conditions was less than 1.5 cm. ‘.‘N extraction,

trapping and conversion

to ammonia

The gas recirculation system shown in Fig. 2 was used to extract and trap the 13Nactivity produced in the graphite target. Following deuteron beam bombardment, the gate valve between the target chamber and the accelerator beam line was closed and the valves between the target and the gas recirculation loop were opened. A measured amount of oxygen gas was admitted into the loop and a thin layer of graphite was then combusted by rapidly raising the graphite temperature using the technique described

980

R. E. SHEFER er aI,

above. During combustion, a peristaltic pump provided a flow rate in the recirculation loop in the range 280-360 std-mL/min. Two identical traps were located in the flow loop, as shown in Fig. 2. Each trap contained 5% NaOH in 2 g of silica gel placed in a 6 mL syringe. This trapping medium was selected based on the results of experiments described in the accompanying paper (Dence et al., 1994) in which this trapping medium was found to have high trapping efficiency for the activity released in the combustion gas stream. The activity in the traps was continuously monitored by placing them in the well of the radioisotope dose calibrator (Capintec CRC-12). After combustion and trapping were complete, the traps were separated and the activity in each trap was independently measured. In several experiments, the graphite was removed from the target chamber following combustion and placed in the well of the radioisotope calibrator in order to measure the residual activity remaining in the lattice. In three experiments, the 13N activity collected in the traps was eluted using 2-3 mL of distilled water. Elution efficiency was determined by measuring the activity contained in the eluate and comparing with the activity contained in the traps prior to elution. In one experiment, the eluted activity was incorporated into [“N]NH3 using a new liquid phase synthetic technique developed at Washington University. Details of this technique are described in the accompanying paper (Dence et al., 1994). The [13N]NH, synthesis system used in this experiment is shown schematically in Fig. 3. The system consists of a 5 mL conical vial (ReactivalTM) modified with a vertical air condenser on top and two side arms to add nitrogen gas and inject the trap eluate. A side-arm condenser about 3.8 cm below the top of the reflux vertical tube is used to direct the stream of nitrogen carrying the [13N]NH, into a receiver. The receiver is another 5 mL ReactivalTM modified by the addition of a side arm. Before the start of a synthesis, the vessel (A) was loaded with 0.3-0.4g of a Raney-Nickel slurry (Aldrich 22,167-8) (Wankat et al., 1963) and 100 PL

of a 50% NaOH solution (Fisher SS254-500). The collecting vessel (B) was loaded with about 1.OmL of 0.1 N HCl, and the side arm of this vessel was connected to a syringe containing 2 g of boric acid (Fisher A-73) which served as a scrubber for any [“N]NH3 that might escape. After combustion, the 13Nactivity collected in the first NaOH/silica gel trap was eluted directly into the Raney-Nickel/NaOH reducing mixture. The nitrogen gas flow was started and vessel A was heated rapidly with a heat gun. The activity in vessel A and in the receiver were monitored with a GM meter (Victoreen Model 290) and heating was stopped when the transfer of activity to the receiver ceased. The activity distilled in the 0.1 N HCl was then measured in a radioisotope calibrator. The chemical form of the distilled activity was determined in separate experiments conducted at Washington University using an identical trapping and elution technique and the chemical synthesis system shown in Fig. 3. In those experiments (Dence et al., 1994), the activity trapped in the 0.1 N HCl was analyzed by IC and found to be [13N]NH3with a radiochemical purity approaching 100%.

Results “N yield at low bombarding energy

Figure 4 shows the 13N saturated yield from ‘*C(d n)13N in a thick graphite target for deuteron energies of 0.8-3.2 MeV. The saturated yields were calculated from the yields measured after 10 min irradiation at each deuteron energy. Also displayed in the figure are saturated yields between 2.0-5.0 MeV measured by Jaszczak et al. (1969). Our measurements are in excellent agreement with the published yields at the high energy end of the range examined in these experiments. Graphite combustion and extraction of “N activity

A series of irradiation and combustion experiments were performed to determine the relationship be-

A

Rat-my-Nickel ’

B

l3N-trap

HCI

Vent

Slurry Fig. 3.

Schematic drawing of the liquid phase [‘-‘N]NH, production

system.

981

‘jN Target for low energy accelerators

,014

0

.

I 1

1 2

’

I 3

’

I 4

.

! 5

Deuferon Energy (MN)

Fig. 4. Measured ‘?(d,n)“N thick target yield at saturation (a). Yields reported by JasTza$ er al. (1969)are also shown

tween the quantity of oxygen gas introduced into the target chamber, the mass and thickness of graphite combusted, and the percentage of “N activity extracted. Activity is produced within a small fraction of one deuteron range of the graphite, however, some diffusion of the 13N-activity away from the graphite surface may occur due to recoil energy imparted to the 13N nucleus and temperature gradients in the graphite target. In order to minimize diffusion, the experiments were performed using the ZL-3 (low porosity) graphite. After each target irradiation with the TCA deuteron beam (1.2 MeV, 5 PA for 2 min to produce 490 PCi of 13Nactivity), a measured amount of oxygen gas was admitted into the target chamber, and the graphite pellet was heated to 750°C to initiate combustion. The pellet was then maintained at 750°C or above until combustion was complete. Since only a small fraction of the graphite pellet was combusted in each experiment, complete combustion corresponded to complete oxygen utilization and was indicated by a drop in the pellet temperature at constant RF power. Following combustion, the graphite pellet was removed from the target chamber and placed in the well of a radioisotope calibrator to determine the residual activity remaining in the lattice. The pellet was also weighed and measured to determine the mass combusted and the approximate thickness of graphite burned from the front face and outer diameter of the pellet. The mass of graphite combusted was found to be linearly proportional to the amount of oxygen admitted to the target chamber. Fig. 5 shows the dependence of the percent of activity extracted on the total mass of graphite combusted and the thickness of graphite removed from the front face of the target. The figure indicates that, for this deuteron beam energy, approx 40mg of graphite

must be cornbusted to extract 99% of the activity produced in the target. Mass was lost almost entirely from the front face and circumference of the pellets, and not from the back surface or threaded stem. This was probably due to the fact that oxygen was introduced into the target chamber upstream of the graphite pellet with the flow directed at the pellet face. Measurements of the target dimensions after this series of experiments gave a value for the corresponding thickness of graphite which must be removed from the front face of the target to extract 90% of the activity of approx 6 pm which is just under half a deuteron range in graphite at 1.2 MeV (R, = 13 pm). Extraction of 99% of the activity required removal of approx 13 pm of graphite. These results are consistent with the expectation that activity is produced within a fraction of a range but show that diffusion of the recoil 13Ninto the lattice does play a role in the depth at which activity is found in the graphite after deuteron irradiation. A series of experiments was performed using both ZL-3 (low porosity) and ECL graphite samples to determine the effect of graphite porosity on 13N extraction efficiency. The results of these experiments are summarized in the upper portion of Table 1. For all measurements, activity was extracted under nearly identical conditions of O2 partial pressure and flow rate after graphite irradiation for 1 min with a 2.4 MeV, 5 PA deuteron beam. The residual activity remaining in the untreated ECL graphite target after combustion was significantly higher than that remaining in the low-porosity graphite, probably due to the increased depth of diffusion of the recoil 13Ninto the lattice in the higher porosity (ECL) graphite. This result indicates that graphite porosity adversely affects 13N extraction efficiency. The extraction of activity from the low porosity graphite was found to be very reproducible. Target 3 listed in Table 1 was used for 6 consecutive irradiation and combustion cycles in which approx

Thickness Cornbusted (pm) 0.0

3.3

6.6

10

13

17

20 t

__ .

.

0

IO

.

.

.

.

20 30 40 60 Mass of Graphite Cornbusted (mg)

. 60

Fig. 5. Dependence of activity extracted on mass and thickness of graphite combusted after irradiation with 1.2 MeV deuteron beam.

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R. E. %!ZFER et al.

Table 1. Dependence of “N extraction efficiency on graphite type and heat-treatment. All targets were irradiated with a 2.4 MeV, 5 (rA deuteron beam for 1min to produce 2.22 mCi of ‘)N activity Target I.D.

o2 fill (std-ml)

Mass change (mg)

Percent residual activity

3 6

Untreated low porosity graphite 270 127 140’ 280 280 NM

1.6 1.7 0.6

4 4

Untreated ECL graphite 280 147t 280 147t

7.6 5.5

I

2 5

Heat treated low porosity graphite NM 280 Heat treated ECL graphite 260 149

6.0 36

NM = not measured. *Mass change and residual activity measured after six consecutive combustions with the same combustion parameters. Listed value is average mass change. tListed value is average mass change over two comhustions with the same parameters.

125 pm was removed from the front face of the target per combustion. The extraction efficiency after the last irradiation was still greater than 98% indicating that a single target sample should be reusable for multiple irradiation and combustion cycles without significant degradation in extraction efficiency. The efficiency of extraction of “N from ZL-3 (Target 2) and ECL (Target 5) graphite samples which had been heat-treated prior to irradiation was also investigated. The results are listed in the lower portion of Table 1. The extraction efficiency from both heat-treated samples for the same 0, partial pressure and flow rate was found to be significantly lower than the corresponding untreated samples. Again, the residual activity remaining in the ECL sample was found to be higher than that remaining in the ZL-3 sample. These results indicate that heat treatment of the graphite pellet is detrimental to extraction efficiency, possibly because the removal of absorbed nitrogen and other gases by heat-treatment allows unimpeded diffusion of the recoil 13N into the graphite lattice. Target behavior during high power deuteron beam bombardment

Experiments were performed to investigate target performance during high power deuteron beam bombardment. Of particular concern were the rate of target outgassing and the rate of diffusion of “N activity into the graphite lattice at elevated temperatures. Graphite pellet cooling during bombardment is primarily by radiation, with some additional cooling provided by conduction to the water-cooled threaded stem. Previous work has shown that nitrogen is first released from graphite heated in vacuum to 1700°C (Kohl, 1960) indicating that target operation at temperatures below this value should not result in loss of “N activity. In order to verify that 13N is retained in the graphite lattice during high temperature operation, the target was irradiated with a high

power deuteron beam. Using a 3.2 MeV deuteron beam, the target current was raised slowly to 70pA (224 W) over a period of approx 1 h and maintained at this value for 10.6min. The pellet temperature equilibrated at 1030°C within 2 min of reaching the maximum irradiation current. The calculated equilibrium temperature for this beam power assuming radiative cooling only is lllO”C, confirming that radiation is the primary cooling mechanism and that only a small fraction (approx 20%) of the beam power is removed by water cooling of the target stem. The measured 13N yield at EOB was 604 mCi which was in good agreement with the calculated yield of 570 _+20 mCi for the bombardment conditions of this experiment. This result confirmed that loss of 13N activity due to outgassing during bombardment did not occur at an operating temperature of approx 1000°C. Additionally, the target vacuum pressure remained well within the required limits for accelerator operation (less than 10-j torr) during bombardment with the 224 W beam, indicating that the outgassing rate of other adsorbed gases in the graphite lattice was within acceptable limits. A second experiment was performed in order to investigate the effect of high temperature operation on r3N extraction efficiency. In order to facilitate comparison with previous extraction experiments performed at low beam power (Fig. 5) the target was first irradiated with a 1.2 MeV deuteron beam and activity was then extracted using the combustion protocol described above. Since the TCA could not deliver a high current beam at this low energy, the graphite temperature was raised to 900°C with the RF coil during irradiation, After irradiation (1.2 MeV, 5 PA for 4 min), the graphite sample was removed from the target chamber and the “N yield was measured to be 913 FCi. This is in excellent agreement with the predicted yield of 9 14 ,uCi, calculated from the data in Fig. 4, again confirming that there was no significant loss of 13N activity during irradiation with the target at elevated temperature. The measured extraction efficiency after combustion of 40 mg of graphite was identical to that obtained previously with a graphite pellet which was not heated during irradiation, thus indicating that there is no significant diffusion of activity into the graphite lattice at elevated temperature. Measurements of trapping eficiency and conversion oj trapped activity to ammonia

A series of trapping experiments was performed using two solid phase NaOH/silica gel traps in series in the recirculation loop, as shown in Fig. 2. In each experiment, the target was irradiated with the TCA deuteron beam, after which the graphite was combusted while trapped activity and target temperature were continuously monitored. The measured time dependence of the trapped activity and the target temperature in a typical experiment are displayed in Fig. 6. The trapped activity reached a maximum

“N Target

for low energy

0.0

0

1

2

3 Time After Energizing RF Coil (mm)

4

Fig. 6. Dependence of target temperature and actual trapped activity on time from start of heating. Activity plotted is not decay corrected.

value approx 3 min after the RF heating coit was energized. The results of the trapping experiments are summarized in Table 2. The irradiation conditions for the first eight entries in the Table were 2.4 MeV, 5 PA for 1 min which produces 2.22mCi of ‘3N activity. The ninth entry corresponds to the production of 9.5 mCi of 13N at 2.4 MeV deuteron energy and the tenth entry corresponds to the production of 202mCi of 13Nactivity at 3.2 MeV beam energy. In the first nine experiments, 275 std-ml of oxygen gas was admitted into the loop following each irradiation, raising the pressure to 440 torr. Helium gas was then added to bring the total pressure to 2-3 psig. In the tenth experiment, the loop was filled with pure oxygen to a pressure of 2-3 psig. The larger quantity of oxygen used in this experiment was required to combust a thicker layer of graphite corresponding to the larger depth of production of 13N at the 3.2 MeV beam energy. The trapping efficiency (defined as the ratio of trapped activity to activity released from the graphite) averaged over the first nine experiments, in which the extraction and trapping conditions were identical, was 78 + 3.5%. Tn each case, greater than 95% of the

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trapped activity was found in the first trap, indicating that a single trap is sufficient. Both ZL-3 (low porosity) and ECL graphite samples were tested and no significant difference in trapping efficiency was found. The results of the trapping experiments can be better understood in terms of measurements performed in a similar combustion and gas recirculation system at Washington University (Dence et al., 1994). In those measurements, gas samples were withdrawn from the recirculating 13N gas system and injected into the column of gas chromatography. It was found that approx 20% of the gas produced in the combustion of irradiated graphite under conditions similar to those reported here was [13N]N,. This indicates that the trapping efficiency of 78% represents nearly 100% of the non-[13N]N, gas released by combustion. A heat-treated sample of ECL graphite was tested in order to determine whether removal of cold nitrogen from the graphite lattice prior to bombardment would reduce the fraction of activity released as [13N]N2, thereby increasing trapping efficiency. The seventh entry in Table 2 shows a trapping efficiency of 72% for this sample, indicating that heat-treatment to remove adsorbed nitrogen does not result in improved trapping efficiency. This result indicates that cold nitrogen trapped in the graphite lattice does not play a significant role in the formation of [13N]N2 in the gas recirculation system during combustion. The tenth experiment listed in Table 2 demanstrates that the extraction and trapping of activity can be extrapolated to the higher 13Nactivity required for the production of clinically significant batches of [‘3N]ammonia. The extraction efficiency measured in this experiment was 98.6% and the decay-corrected trapping efficiency (for a single trap only) was somewhat lower than, but within two standard deviations of the average efficiency measured for the smaller 13N activities. The measured peak in real trapped activity in this experiment (not decay-corrected) was 83 mCi indicating that saturation of the trapping medium does not occur up to at least this value of 13Nactivity. The trapping efficiency was found to depend strongly on the gas flow rate in the target flow loop

Table 2. Summary ofresults of “N trapping experiments. Except as noted, targets were irradiated with a 2.4 MeV, 5 JIA deuteron beam for 1min to produce 2.22 mCi of “N activity Target material Low porosity Low porosity Low porosity Low porosity ECL ECL Heat-treated ECL Low porosity Low porosityf Low porosity5

First trap (mCi EOB)

Second trap (mCi EOB)

1.59 1.65 1.69 L.63 1.54 1.65 1.01

0.060 0.008 0.042 0.093 0.018 0.067 0.022 0.217 -

I.7611 7.43 137

Extraction efficiency* (%) NM NM NM 98.3 92.4 94.5 64 NM NM 98.6

Trapping efficiency7 (%) 75 76 79 79 76 82 72 80 82 68

*NM = not measured. In these cases, the extraction efficiency was assumed to be 98.5%. tRatio of total trapped activity to activity extracted from graphite. JBombardment conditions corresponding to the production of 9.5 mCi. §Bombardment conditions corresponding to the production of 202 mCi at 3.2 MeV, TThis single trap consisted of 2.4 g of Raney-Nickel/NaOH in silica gel.

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(Fig. 2). A flow rate of 140std-mL/min yielded a trapping efficiency of only 41%, or approximately half the trapping efficiency obtained with the 280-360 std-mL/min flow rate used in the experiments described above. No difference in trapping efficiency was found within this higher range of flow rates. The rate of combustion and trapping was found to decrease with decreasing partial pressure of oxygen. Since the total amount of 0, gas is fixed by the mass of graphite to be combusted, case must be taken to minimize the total loop volume in order to maintain high O2 partial pressure. In the target system used in these experiments, a further increase in the O2 partial pressure was not practical since the loop volume was dominated by the volume of the target chamber itself. In three experiments, the traps were eluted and the efficiencies of elution of the traps were measured. The elution efficiencies were found to be 89, 86, and 8 1%, for an average elution efficiency of approx 85%. In one experiment, the activity was eluted directly into vessel A of the ammonia production system shown in Fig. 3. The conversion efficiency from eluate to ammonia was measured to be 68%.

Discussion The primary accomplishments ported in this paper are:

of the work re-

(1) A windowless graphite target which allows rapid, in situ extraction of 13N activity from the graphite matrix by combustion of a thin layer of graphite was designed, fabricated and tested. Combustion and extraction protocols were developed and the repeatable extraction of greater than 99% of the 13N activity produced in the target was achieved. High extraction efficiency was obtained for a single graphite pellet over multiple irradiation and combustion cycles, indicating that one pellet should be reusable for multiple 13N production runs. (2) Target performance was found to be unaffected by operation at elevated temperature. Operation of the target at temperatures between 900-1030°C during irradiation resulted in no loss of 13N activity by desorption and in no significant increase of the depth of diffusion of the recoil 13N in the graphite lattice. These results confirm that a target with the primarily radiatively-cooled design used in these experiments can successfully operate at temperatures of at least 1000°C during high power deuteron beam bombardment. (3) Efficient trapping of the 13Nactivity released by combustion of the graphite in a reusable, solid phase NaOH/silica gel trap was demonstrated. Trapping fractions of 78% (decay corrected) were obtained. The total time required for the extraction and trapping of 13N activity was approx 3 min. (4) Trapped activity was successfully eluted and converted to ammonia using a chemical synthetic technique developed at Washington University in

which the eluate is catalyzed with Raney-Nickel at elevated temperature (Dence et al., 1994). An average elution efficiency of 85% and an efficiency of conversion of the eluate to [13N]NH3of 68% were measured. These results are in good agreement with the results obtained in three experiments with an identical chemical synthesis system at Washington University in which a 90% elution efficiency and a 64% efficiency of conversion to ammonia were measured. In those experiments the time required for elution and synthesis was less than 5 min. (5) Trapping of up to 83 mCi of actual 13Nactivity in a single S%NaOH/silica gel trap was demonstrated. This result, taken together with the measured elution and synthesis efficiencies and times given above, indicates that it should be possible to produce 30 mCi batches of [13NJNH3using this technique. This batch size is more than adequate for most research and clinical needs. The results of these experiments can be used to estimate the 13N activity which must be produced in the graphite target to yield clinically useful batches of [13N]NH, (30 mCi or more). The total decay corrected yield of activity induced in the graphite target to ammonia is the product of the extraction efficiency (99%), trapping efficiency (78%), efficiency of elution of the traps (SSO/) and conversion of the eluate to ammonia (68%). In the experiments reported above, the overall decay corrected efficiency for conversion of target activity to ammonia was thus 45%. Using the times required for the extraction, trapping, elution and synthesis and steps measured at SRL and Washington University (Dence et al., 1994), the minimum conversion time is approx 8 min. Thus, it is reasonable to assume that the entire process could be completed in 10 min (or less) in an automated system. Production of a clinically useful batch (30 mCi) of [‘3N]ammonia would therefore require a target activity of approx 135 mCi. The ‘zC(d,n)‘3N thick target yields in graphite at low deuteron beam energy presented in Fig. 3 show that 135 mCi of 13Nactivity can be produced in a 20 min target irradiation time with beam currents ranging from 600gA at 1.0 MeV down to 15pA at 3.2 MeV. These beam currents are within the capabilities of presently available electrostatic deuteron accelerator technology over the stated energy range. At the high end of the range (3 MeV and above), cyclotron accelerators can also deliver the required beam current. The use of the 13N production target described in this paper will make possible the development of dedicated [i3N]ammonia generators using compact, low-cost, low energy deuteron accelerators. A selfshielded generator of this type, which uses a 1.2 MeV electrostatic deuteron accelerator in conjunction with the 13N target, extraction and ammonia synthesis system described above is currently under development at Science Research Laboratory (Klinkowstein

‘)N Target for low energy accelerators

985

Ammonia Synthesis System Control Electronics

L

Graphite Target and Shield

1

1.2 MeV Deuteron Accelerator

n 10

Fig. 7. Schematic drawing of [“Nlammonia generator.

rt al., 1993). A schematic drawing of this system, including the 13N extraction and ammonia synthesis system and controls, is shown in Fig. 7. The small size of the accelerator (1.6 m long and 0.75 m in dia) and the modest radiation shielding requirements at low deuteron bombarding energy allow the entire system to be incorporated into a cabinet of approximately the same dimensions as a large office copying machine. Such a generator could be used as a stand-alone system in PET centers which have access to “F from local-area higher energy accelerator sources, or to increase the production capabilities of larger PET centers which already have in-house ‘*F production capabilities. It would provide an attractive alternative to the costly 82Sr/s2Rb generators currently used at some PET centers for myocardial perfusion studies (Mullani et al., 1983; Goldstein et al., 1983, 1986). In the future, the use of such a system in a mobile PET facility could also be contemplated. Acknowledgements-This work was supported by the National Institutes of Health Grants lR43HL48969 and 2R44CA53953, and by the Ballistic Missile Defense Organization Contract SDI084-89-C-0049.

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