On-line interconversion of [15O]O2 and [15O]CO2 via metal oxide by isotopic exchange

Appl. Radiaf. hr. Vol. 39, No. 12, pp. 1207~1211, 1988 Inr. J. Radial. Appl. Ins~rum.Parr A Printed in Great Britain. All rights reserved

0883-2889/88 163.00+ 0.00 Copyright 0 1988 Pergamon Press plc

On-line Interconversion of [*50]02 and [150]C02 via Metal Oxide by Isotopic Exchange REN

IWATA,* and

Cyclotron

and Radioisotope

TATSUO IDO, YOSHIKI SHIGEKI YAMAZAKIT Center,

Tohoku

University,

FUJISAWAt

Aramaki,

Sendai

980, Japan

(Received 2 February 1988; in revised ,firm 26 April 1988) A novel method has been developed for the on-line production of ‘50-labelled gases. The I50 exchange reactions between 0, and CO, assisted by a metal oxide catalyst were successfully applied to on-line interconversion of [“O]O, and [‘50]C0, with Hopcalite II(Cu0 40% and MnO, 60%). The conversion reactions were optimized as to the reaction temperature, the amount of the catalyst, and the flow rate

of a gas added for oxygen exchange. [‘50]0, was converted to [“O]CO, in a 80% yield with 0.7 g of Hopcalite II and 100 mL/min of CO, at 5OO”C,and [‘50]C0, to [“O]O, in 70% with 100 mL/min of 0, at 650°C. The radiochemical purities of the ‘50-labelled gases converted under the optimal conditions were high enough for clinical studies using the standard dilution and inhalation procedures.

Introduction A large number of radiopharmaceuticals labelled with “C, 13N, “0 and ‘*F have been synthesized for positron emission tomographic (PET) studies in nuclear medicine. [“O]O,, [‘sO]CO and [‘50]C0,, the simplest compounds among these radiopharmaceuticals, have been of growing importance for brain studies since production methods for the “0-1abelled gases were developed and established (Clark and Buckingham, 1975). They have been used for nearly two decades without any significant modification or improvement (Welch and Kilbourn, 1985; Strijckmans et al., 1985; Clark et al., 1987). 150-gas production is performed as follows: [“O]O, and [‘50]C0, are produced using the 14N(d, n)“O reaction from nitrogen gas containing their respective carriers of 0, and CO*. [“O]O, is converted to [‘50]C0 with activated charcoal heated at about 1000°C. Since routine PET studies require the combined use of [‘50]02 and [‘50]C0,, a rapid alternate exchange of the target gas from one to the other is necessary. Therefore, the on-line production of the above three radioactive gases using a single target gas is of increasing interest. The on-line conversion of [‘50]0, to [‘50]C0, may be achieved using a low temperature combustion of [‘50]0, on activated charcoal, but this method is not efficient (Clark et al., 1987). *Author for correspondence. tvisiting scientists from the Engineering Nippon Kokan K.K., Kawasaki-k& Japan.

Research Center, Kawasaki, 210

The present paper describes an on-line method for mutual conversion of [“0]02 and [“O]CO, via metal oxides by isotopic exchange. Conversion yields have been correlated to the amount of metal oxide, the furnace temperature and the flow rate of a gas added for exchange of I50 with a starting ‘SO-labelled gas for efficient production. The present on-line I50 exchange method allows all the 150-labelled gases to be continuously produced with a single target gas without interruption of the irradiation.

Materials A continuous

and Methods

flow of [‘50]0, or [“O]COZ was obtained by deuteron irradiation of a N, gas containing 0.25 ~01% 0, or 2.5 ~01% CO,, respectively, flowing through an aluminum target chamber using the j4N(d, n)150 reaction. [‘50]C0 was produced by on-line conversion of [‘50]02 with activated charcoal heated at 1000°C. These ‘50-labelled gases were purified with activated charcoal or soda lime, and then delivered to the PET site at a flow rate of 250 mL/min. Their radiochemical purities determined by gas chromatography (GC) were usually more than 99 and 98%. Figure I shows the experimental system used for the present study. The exchange gas of 0, or CO, was added to the radioactive gas before entering the furnace at a flow rate adjusted with a mass flow controller (Model 410, STEK Inc., Japan). A quartz tube for the metal oxide was of 12mm inner diameter. Commercial metal oxides were used without

&N

1208

IWATA

et al.

Radioactivity detector-l

He in (Path

S)

[“OlGas In

(8_ r_‘_ o,.r+&Y?!J Automatic flow controller

m L

I Furnace

Fig. 1. A flow chart

of the experimental

further treatment. Hopcalite I (10-24 mesh, CuO 30%; MnO, 50%; Ag,O 5%, Co,O, lS%, Gasukuro Kogyo Co. Ltd, Japan), Hopcalite II (lo-24 mesh, CuO 40%; MnO, 60%, Nakarai Chem. Ltd, Japan), CuO (Wire for elemental analysis, Merck) and MnO, (Granular, Wako, Japan) were used. The radioactivity of the flowing gas was monitored at the both input and output ports of the system using a small semiconductive detector (Model RISlO, Shimazu Co., Japan). Since the input radioactivity was not kept constant during the experiment, a correlation was always obtained between the input radioactivity (As,) and the output one (A,,) by passing the target gas through the short path (Path S) when any experimental condition was changed, and then the path was switched to the furnace (Path R) with a 3-way valve. After both the input and output radioactivities (A,, had reached equilibrium, a and A,,, respectively) small portion of the reaction gas was sampled with a 6-way valve for analysis by GC on Porapak N or Molecular Sieve SA. Thus, a conversion yield of [“0]02 to [“O]CO, or [“O]CO, to [‘50]0, was determined using the following equation: Yc = (A,olA,,)I(A,,IAs,)*P,, where

Yc was a percentage

conversion

Table

yield and PGc

I. Yields of “0

exchange

Radioactivity detector-2

system.

was a percentage radiochemical purity verted molecule determined by GC.

Results and Discussion In our preliminary study [“O]CO, was passed through a column of Pt wires with 0,. As shown in Table 1 only 10% of 150 was found in 0, at 950°C and no radioactivity was lost on a quartz tube or wool. This result indicates that no oxygen exchange between CO, and 0, or between CO, and SiO, took place at temperatures, at least, below 8OO”C, and consequently that any exchange of I50 between 0, and CO, observed in the present study was due to the presence of metal oxide. Such heterogeneous oxygen exchange reactions have been investigated using a stable oxygen isotope to characterize metal oxide as a catalyst. From the kinetic studies of oxygen exchange reactions using “O,, it has been proposed that most of the metal oxides exchange their surface oxygens with gaseous oxygen molecules mainly by a dissociative atomic mechanism and in some oxides by a molecular reaction (Winter, 1968). On the other hand, oxygen exchange between CO, and some metal oxides readily occurs through carbonate formation (Keulks and Chang, 1970; Peri, 1975). These earlier

reactions

assisted

by some metal oxldes % Distribution

Temperature ( ‘C) 230 205 200

Input

“O-gas

Exchange

gas

of “0

0,

CD*

02 CO, co

CO,. 100 mL/min 0,. 100 mL/min O,, 100 mL/min

86 2
2 74 41

650 650 650

0, CO* co

CO,, 100 mL/min 0,. 100 mL/min O,, 100 mL/min


63 4
cue 2.7 g

650 700

CO* co

O,, 100 mL/min O,, 100 mL/min


99 II

MnO, I.1 g

650 650

0, CD*

CO,, 100 mL/min O,, 100 mL/min

20 57

60 26

Pt

800 950

co, CD*

O,, 70 mL/mm O,, 70 mL/min

12 IO

98 90

Metal oxide Hopcalite 0.7 g

I

Hopcalite 0.7 g

II

NS

of the con-

Interconversion

300

400

500

of [‘50]0,

600

Furnace Fig. 2. Correlations

and [‘50]C0,

300

400

1209

500

600

temperatureW3

yield and the reaction temperature with Hopcalite II. Flow rate of the exchange gas: lOOmL/min.

between

the conversion

studies support the theory that the surface of the metal oxide plays an important role in I50 exchange reactions between 0, and CO, in the present study. Table 1 lists the typical results obtained for the metal oxides investigated. Hopcalites are the oxidative catalysts, consisting mainly of CuO and MnO,. Since Hopcalite I contains Ag,O which is decomposed at 3OO”C, the exchange reactions were carried out below 300°C. Although no oxygen exchange was observed between CO2 and 0, with a small amount of the catalyst, a considerable decrease in the radioactivity after passing through the catalyst suggests that oxygen exchange between the gaseous molecules and the catalyst occurred to some extent. Hopcalite II showed remarkable oxygen exchange at increased temperatures, whereas MnO, exchanged I50 to a lesser extent by itself, and CuO alone was almost inactive towards CO,. Hopcalites are known as catalysts for combustion of CO at ambient temperature. [‘50]C0 was converted to [‘50]C0, in a less than 50% yield with 0, and Hopcalite I, while only

[“O]O, was obtained with Hopcalite II. This can be explained by a subsequent oxygen exchange reaction after [‘50]C0 has been oxidized to [‘50]C02 with Hopcalite II. The same reaction seems to have occurred in [‘50]C0 combustion with CuO and 0,. However, this is not consistent with the fact that [‘50]C0, is inert towards CuO. It is beyond the scope of this paper to speculate on a mechanism of this interesting disproportional distribution of I50 resulting from the CuO-catalyzed oxidation of [“O]CO. The oxygen exchange reactions with Hopcalite II were optimized as to the reaction temperature, amount of the catalyst and the exchange gas, since this catalyst showed a high efficiency for I50 exchange between 0, and CO,. The correlations between these parameters, obtained with a constant exchange gas flow rate of 100 ml/mm, are shown in Figs 2-4. The “0 was rapidly incorporated into the catalyst with increasing temperature and at the same time it began to be transferred to the exchange gas in the conversion of [‘50]02 to [‘50]C0, or vice versa. The

0 3cO

400

500

600

Furnace Fig. 3. Correlations

between

300

400

500

600

temperature(%)

the nonconversion yield and the reaction temperature Flow rate of the exchange gas: 100 mL/min.

with Hopcalite

II.

1210

REN IWATA

300

400

500

600

Furnace Fig. 4. Correlations

between

400

300

500

600

temperature(%)

yield into the Hopcalite II and the reaction temperature. Flow rate of the exchange gas: lOOmL/min.

the incorporation

decrease in the conversion yield over 500°C as seen in Fig. 2 was compensated for by the increasing “0 activity retained by the catalyst (see Fig. 4), probably due to the increase in the number of exchangeable oxygens in the surface of the catalyst as reported by Peri (1975). The difference in the mechanism of “0 exchange between the two conversions is suggested by the different features of the correlation curves of I50 incorporation into the catalyst, given in Figs 3 and 4. Exchange reaction with O2 seems to be more drastically dependent on reaction temperature than CO,, and the latter reaction seems to be more dependent on the amount of Hopcalite II, suggesting that the catalyst has less exchangeable sites for CO2 than 0, per unit surface area. Less than 0.16 g of the catalyst is obviously insufficient for efficient conversion, especially of [‘50]C0, into [150]02. This can be more clearly seen in Fig. 5 which shows the correlations between the conversion yield and the flow rate of the exchange gas at a constant gradual

‘500 -q 60

62 al.

temperature of 65O’C. The conversion yields obtained with less than 0.15 g of the catalyst decreased with increasing flow rate, suggesting that some of the input radioactive gas passed through the column without contact with the catalyst, while the yields were improved by increasing the flow rate with a more than 0.72 g of the catalyst. The amount of 2 g or above is, however, apparently excessive. Therefore approx 0.7 g of Hopcalite II is estimated to be the optimal amount. In addition to conversion yield, radiochemical purity is also an important parameter for clinical use of ‘50-labelled gases. Figure 6 illustrates the relationships between the radiochemical purity and the reaction temperature. When [“O]O, was converted to [150]C02 using 100 mL/min of CO,, the [150]C0, obtained was practically pure at 500°C in a sufficiently high conversion yield of 80% with 0.72 g of Hopcalite II. On the other hand, [150]C02 required a higher temperature for efficient conversion into

c’sooo21500

d500

-1

t

2 5 sot~~~~ z

‘5.

_

c .$ 40t

_

c' 00 20-

0

t

4a

4Q

I 50

COP flow

I 100

I 150

rate(mL/min)

I 200

0

50

O2 flow

I 100

150

200

rate(mL/min)

Fig. 5. Effects of flow rate of the exchange gas on the conversion yields with Hopcalite II. Reaction temperature: 650°C.

Interconversion

Thus, by ‘50-labelled or [‘50]C02 tage will be

1211

400

between

radiochemical purity and the reaction temperature rate of the exchange gas: 100 mL/min.

500

600

+ c + PO

300

400

500

600

temperature(T)

[“O]O,, and a lower yield of 68% with a slightly lower radiochemical purity of 95% was obtained at 650°C. However, it should be noted that [“O]C02 can be easily removed from [“0]02 by absorption with soda lime, but that it is practically’ impossible to remove [‘50]0, from [“O]C02. Therefore, conversion of [‘50]C02 into [‘50]0, followed by removal of unconverted [‘50]C02 with soda lime is recommended for routine on-line preparation. A remarkable feature of the present method is that both [‘50]02 and [‘50]C0, can be produced using the single target gas. Votaw et al. (1986) have recently reported that use of the Edison lamp in the target of N, containing O2 allows a selective on-line production of [“0]02, [‘50]C02 and [“O]CO by varying the power supplied to a carbon filament (Votaw et al., 1986). Although the present conversion method cannot directly give [‘50]C0 owing to high toxicity of CO for use as an oxygen exchange gas, it can be produced by conversion of [“O]CO, with charcoal heated at about 1000°C according to the following reaction as used in the reduction of [“O]CO, to [“C]CO (Clark et al., 1967) PO0

and [i50]C0,

300

Furnace Fig. 6. Correlations

of [“O]O,

+ co.

using the present method the three gases can be obtained from either [‘50]02 produced by the irradiation. This advanuseful not only for saving time required

with Hopcalite

II. Flow

for a target exchange but also for reducing running costs especially when the “N (p, n)“O reaction is used with a “N-enriched nitrogen gas target.

References J. C., Matthews, Sylvester D. J. and Vonberg D. D. (1967) Using cyclotron-produced isotopes at Hammersmith Hospital. Nuckmics 25, 54. Clark J. C. and Buckingham P. D. (1975) Short-lived Radioactive Gases for Clinical Use. Butterworths, Lon-

Clark

don. Clark J. C., Crouzel C., Meyer G. J. and Strijckmans K. (1987). Current methodology for oxygen-15 production for clinical use. Appl. Radial. Isot. 38, 597. Keulks G. W. and Chang C. C. (1970) The kinetics and mechanism of carbon monoxide oxidation. J. Phys. Chem. 74, 2590. Peri J. B. (1975) Oxygen exchange between Ci*O, and “acidic” oxide and zeolite catalysts. J. Phys. Chem. 79, 1582. Strijckmans K., Vandecasteele C. and Sambre J. (1985) Production and quality control of ‘5O, and Ci50, for medical use. Inr. J. Appl. Radial. Isot. 34, 279. Votaw J. R., Satter M. R., Sunderland J. J., Martin C. C. and Nickles R. J. (1986) The Edison lamp: O-15 carbon monoxide production in the target. In Proc. 6th Int. Symp on Radiopharmaceutical Chemistry, Boston, p. 183. Welch M. J. and Kilbourn M. R. (1985) A remote system for the routine production of oxygen-15 radiopharmaceuticals. J. Labelled Compd. Radiopharm. 22, 1193. Winter E. R. S. (1968) Exchange reactions of oxides. Part IX. J. Chem. Sot. A 2889.