US3694313A - Production of high purity 123i - Google Patents

Abstract

BOMBARDING A TELLURIUM TARGET WITH A BEAM FROM AN ACCELERATOR PRODUCES 123XE WHICH IS CARRIED AWAY BY A FLOWING GAS STREAM. CONTAMINANTS ARE REMOVED FROM THE GAS, AND THE REMAINING XENON DECAYS TO 123I WHICH IS READY FOR USE AS A RADIOPHARMACEUTICAL IN WHICH LOW RADIATION EXPOSURE IS DESIRED AS IN DIAGNOSTIC STUDIES.

Description

Sept. 26, 1972 J. w. BLUE ET AL PRODUCTION OF HIGH PURITY'231 2 Sheets-Sheet 1 Filed Oct. 2, 1969 9 0 f w 0 m INVENTORS JAMES W. BLUE WAYNE R. SMITH By VINCENT J. 5000 J Mal/W ATTORNEYS Sept. 26, 1972 Filed 001:. 2. 1969 J. w. BLUE ETA!- PRODUCTION OF HIGH PURITY'ZBI 2 Shoots-Shoot 2 so P as FIG.4

lN VENTORS v JAMES W. BLUE WAYNE R. SMITH VINCENT J. SODD QM fiw ATTORNEYS United States Patent U.S. Cl. 176-11 1 Claim ABSTRACT OF THE DISCLOSURE Bombarding a tellurium target with a beam from an accelerator produces Xe which is carried away by a flowing gas stream. Contaminants are removed from the gas, and the remaining xenon decays to 1 which is ready for use as a radiopharmaceutical in which low radiation exposure is desired as in diagnostic studies.

ORIGIN OF THE INVENTION The invention described herein was made by employees of the United States Government and may be manufactured and used by or for the Government for governmental purposes without the payment of any royalties thereon or therefor.

BACKGROUND OF THE INVENTION This invention is concerned with the production of high purity radioiodine for thyroid measurements and as a general radionuclide. The invention is particularly directed to a method of producing 1 by bombarding Te or Te with a beam that is within the energy limitations of a compact cyclotron.

Radioactive iodine is used for medical diagnostic studies. The isotope 1 has been used for this purpose because of its availability. The substitution of I for 1 has been proposed in studies where the amount of radiation exposure to a patient is of prime concern. Because of the shorter half-life and the decay by electron capture, the radiation exposure received by the patient from 1 is about 4 that of an equal amount of 1. Another factor is that the gamma ray energy of 1 is 159 kev. compared to 364 kev. of 1. Collimators operate more effectively with this lower energy, and they are less bulky.

It has been proposed that 1 be produced by several methods utilizing Te (oz, 3n); Sb (0:, 2n); Te (p, n); and Te (He 2n) reactions. However, the contaminants produced from these reactions prevent the full benefit of the 1 from being achieved. The advantage of lower radiation exposure with the use of I is only fully realized if the contamination by other radioiodines is small. By way of example, a 1% contamination of 1 with 1 doubles the patient radiation exposure.

Most of the 1 used for nuclear applications has been made by two methods using large cyclotrons to produce Te (p, n) and 5b (a, 2n) reactions. While these two methods give yields of 1 which are adequate for the diagnostic studies, the processes are expensive because of the cost of the large cyclotrons. Also, contamination in the amount of 0.5 to 0.9% of 1 is encountered. Another problem is that both methods require dissolution of the target material in sulphuric acid and subsequent distillation of I into NaOH. Further, the target material must be chemically recovered, and this increases the production cost.

SUMMARY OF THE INVENTION These problems have been solved by the present invention which utilizes a compact cyclotron to bombard 'ice an enriched Te or Te target with He of energy equal to 30 mev. or less to produce Xe according to a Te (He 2n), Xe or Te (He 3n) Xe reaction. The Xe is transported from the target in a gas stream to low temperature traps where the undesirable iodine contaminants are removed. The xenon is held for a period of time sufiicient for it to decay to 1.

OBJECTS OF THE INVENTION It is, therefore, an object of the invention to produce 1 having suflicient purity for use as a radiopharmaceutical.

Another object of the invention is to provide a method of making high purity 1 using a compact cyclotron without the dissolution of the target together with the chemical separation of 1 and the subsequent chemical recovery of the target.

A further object of the invention is to provide a reusable generator for producing large amount of 1 wherein Xe is physically separated from a tellurium target.

These and other objects of the invention will be apparent from the specification which follows and from the drawings wherein like numerals are used throughout to identify like parts.

DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view of a generator constructed in accordance with the invention for producing radioactive iodine;

FIG. 2 is a schematic view of apparatus for producing radioactive iodine by a cyclic method in the part of the cycle in which the target material is being bombarded;

FIG. 3 is a schematic view of a portion of the apparatus shown in FIG. 2 connected to cold traps; and

FIG. 4 is an enlarged partial view of a section of the apparatus shown in FIG. 2.

DESCRIPTION OF THE PREFERRED EMBODIMENT Referring now to FIG. 1 a target assembly 10 constructed in accordance with the present invention is mounted in the beam duct 12 of an accelerator such as a 60-inch cyclotron. The target assembly 10 utilizes a cylindrical housing 14 for containing a target material 16. The housing 14 is preferably of aluminum, and its temperature is controlled by circulating water in a cooling system 18.

A porous plate 20 supports the target material 16 and separates the housing 14 into a pair of chambers 22 and 24. The target material 16 is in the form of a powder which is preferably held against the porous plate 20 by a screen 26.

A thin metal foil window 28 separates the cyclotron vacuum system from the front target chamber 24. A window 28 of 7 mg./cm. aluminum has been satisfactory. An insulator 30 extending about the periphery of the cyclotron beam duct 12 electrically isolates the target assembly 10 from the cyclotron.

A tube 32 connects the chamber 22 to a cold trap 34. Tygon tubing has been satisfactory. The trap 34 comprises a U-tube 36 immersed in a coolant in an insulated container 38. A 4 inch copper U-tube surrounded by solid CO in a Dewar has been satisfactory. The Dry Ice maintains the trap 34 at a temperature of -79 C.

A valve 40 connects the Dry Ice trap 34 to a second cold trap 42. A inch copper U-tube 44 immersed in liquid nitrogen in a Dewar 46 has been satisfactory. The liquid nitrogen maintains the trap 42 at a temperature of 196 C.

A valve 48 connects the liquid nitrogen trap 42 to a tube 50 that enters a self-contained gas pump 52. The chamber 24 is placed in communication with the pump 52 through a tube 54.

In operation, target material 16 of enriched tellurium powder is spread uniformly on the porous plate 20 to form a 20 to 90 mg./cm. layer. The retaining screen 26 is placed in contact with the tellurium powder, and the metal foil window 28 is mounted on the housing 14 to close the chamber 24.

A beam of helium particles of energy equal to about 40 mev. or less from the cyclotron beam duct 12 passes through a carbon collimator 49. The beam penetrates the foil window 28 and bombards the tellurium target. This bombardment of the tellurium produces xenon in accordance with the reactions Te 3n); Te (He' Zn); or Te (He 3n).

A flow of helium gas is passed through the tellurium powder and porous plate 20 to carry away the Xe into the Dry Ice trap 34 and then into the liquid nitrogen trap 42. By utilizing a closed loop system as shown in FIG. 1 a gas flow rate may be used that both transports the xenon and cools the powder target material while conserving the helium gas.

The conservation of the helium gas is not an important consideration when very low flow rates are used. In such cases a single pass system of the type shown in FIG. 3 is used. This arrangement eliminates the pump, and no evacuation of the system is required because the single pass system can be flushed. However, with such low flow rates no cooling of the target is realized, and the gas is only utilized to carry the xenon to the cold tra I t will also be appreciated that a high flow rate in the closed system may be suflicient to maintain the tellurium in contact with the porous plate 20 without using the screen 26. However, such high flow rates may carry impurities through the trap 34 into the trap 42.

The helium carries the xenon from the target assembly through the tube 32 into the Dry Ice trap 34. Contaminants with freezing points higher than -78 C. are frozen out of the gas stream. These contaminants cling to the walls of the cold trap 34. Among the contaminants removed in the trap 34 are the undesirable 1, I, and 1.

The helium gas flow then carries the xenon into the liquid nitrogen trap 42 where the xenon and other products with freezing points between 79 C. and 196 C. are frozen out. The helium gas is then recirculated through the pump 52 and lines 50 and 54 back to the target assembly 10.

After bombardment the liquid nitrogen trap is sealed by closing the valves 48 and 40. The U-tube 44 is removed from the liquid nitrogen in the container 46 and set aside until the 1 ingrowth is optimized. The 2.1-hour Xe decays to I in about four to eight hours. This time may be used to transport the 1 from the cyclotron to a laboratory.

After waiting for the Xe to decay, the U-tube 44 is flushed with helium gas to remove remaining Xe and Xe. The trap is rinsed with dilute NaOH and the solution is counted to ascertain the presence of I. The 1 is placed in a suitable chemical form for its ultimate medical use.

Direct tagging of organic molecules is possible in the trap 42. By Way of example, macroaggregated serum a1- bumen has been tagged with I by merely contacting a solution with the trap 42. The bulk gas temperature at a helium flow rate of five standard liters per minute exiting a trap 50 centimeters long and 3 millimeters in diameter is approximately the temperature of the wall of the trap. With such a flow rate the helium would cool the target material 16 and the gas temperature would be lowered enough to freeze the radio xenon. However, at such flow rates the radioiodines do not stick to the wall of the U-tube 36, and the amount of *I in the liquid nitrogen trap 42 is excessive. At the five liter per minute flow rate the gas is not in the Dry-Ice trap 34 long enough to insure complete radioiodine diffusion to the wall of the U- tube 38. This results in low trap elliciency.

Reducing the flow rate to 0.02 liter per minute increases the efiiciency of the Dry Ice trap 34 to about 100%. However, no cooling of the target material 16 is realized.

A flow rate of 10 liters per minute is found to be adequate to maintain the tellurium powder target material 16 in contact with the porous plate 20 without using a retaining screen 26. This flow rate is also adequate to cool the target material 16 sufficiently to avoid deterioration in the beam. However, this flow rate forces many contaminants from the Dry Ice trap 34 into the liquid nitrogen trap 42 and bafiling is required in the trap 34.

The generator shown in FIG. 1 has an advantage in that the yield per hour of bombardment is nearly inde pendent of bombardment time. Thus, in utilizing a small cyclotron for the production of large amounts of I, the length of bombardment time would be determined from schedule consideration or a minimization of trap changes rather than from optimizing the yield.

DESCRIPTION OF AN ALTERNATE EMBODIMENT A cyclic system for producing 1 is shown in FIG. 2. In this apparatus the tellurium is bombarded for a definite period of time and kept cold during this period so that no Xe escapes. The bombardment is terminated, and the tellurium target is heated to a temperature sulficient to remove all the Xe. Provision is made for a controlled heating cycle so that all of the xenon is diffused from the tellurium at a temperature low enough to insure that none of this tellurium is vaporized and lost from the system. The same target can be used for successive bombardments by repeating the cycle.

The cyclic method utilizes a target assembly 60 mounted in a housing 62. The target assembly 60 includes a plate 64 on the end of a tubular member 66. The plate 64 is preferably copper and forms the end of a chamber 68 which is kept lfilled with liquid nitrogen by an automatic filling system 70.

Target material 72 in the form of tellurium powder is contained in a small depression 74 in the plate 64, and aluminum foil cover 76 is mounted over the depression 74 by a ring 78. A ball valve 80 is mounted on the housing 62 adjacent the target assembly 60. A tubular passage 82 extends from the opposite side of the valve 80. This passage is mounted on the cyclotron beam duct 12 by a flange 84.

In operation, the system is evacuated by opening the valve 86 connected to a vacuum pump 88. A beam from the duct 12 passes through the passage 82 and valve 80 toward the target assembly 60. After passing through a carbon collimator 90 the beam strikes the target material 72.

At the end of the bombardment period the ball valve 80 is closed. The target assembly 60 is kept at high vacuum conditions within the housing 62 while the assembly is removed from the cyclotron beam duct 12.

A plate 92 is mounted on the flange 84 as shown in FIG. 3. A foil cutter 94 is mounted on a tubular handle 96 that extends through the plate 92. The space in the passage 82 between the valve 80 and the plate 92 is evacuated by opening the valve 86 to the vacuum pump 88.

The ball valve 80 is then opened, and the tubular handle 96 is pushed through a sliding seal 98 until the aluminum foil cover 76 is cut in the manner shown in FIG. 4. When the foil cutter 94 is fully inserted its end is received in a circular groove 98 at the bottom of the depression 74 in the plate 64 as shown in FIG. 4.

The opposite end of the tubular handle 96 is connected to a tube 100 for placing the target assembly in communication with cold traps 34 and 42 through a tube 32 in a manner previously described in connection with FIG. 1. This embodiment does not use a recirculating system. The system is vented through an oil bubbler 102.

With the cutter 94 fully inserted as shown in FIG. 4 helium gas is slowly admitted to the system by opening a valve 104 that is connected to a suitable gas supply. When the pressure reaches the desired level, preferably one atmosphere, valve means 106, such as a clamp, on the flexible tube 100 is opened. The helium flows through the valve 80 and around the end of the cutter 94 in the groove 98 to the tubular handle 96. This gas carries the xenon to the cold traps 34 and 42 in the manner previously described.

The helium flow between the cutting edge of the cutter 94 and the groove 98 is then adjusted to a low rate, such as about 20 milliliters per minute. Power is supplied to a heater 108 that is inserted in the tubular member 66 in the liquid nitrogen container 68. The heater 108 is in contact with the back of the plate 64 to heat the tellurium powder 72. The temperature of the plate 64 is monitored by a thermocouple 110.

It will be appreciated that the Xe produced during the bombardment in the cyclic system shown in FIGS. 2 and 3 is not efiective in producing 1 if it decays in the target material before it is removed in the heating cycle. The length of the radiation should not exceed two hours followed by heating.

We claim:

1. A method of producing high purity radioactive 1 with a compact cyclotron as a source of a He beam at an energy up to 30 mev. comprising the steps of mounting a target in powder form of an isotope from the group consisting of Te and Te in a chamber, mounting said chamber on said cyclotron, evacuating said chamber, bombarding said target with said He beam to produce Xe for a period of up to two hours, cooling said target with liquid nitrogen during bombardment for preventing escape of Xe, sealing said target after bombardment, removing said sealed target from said cyclotron, connecting a source of helium gas to said target, heating said target to evaporate said Xe, injecting helium into said chamber to raise the pressure of same to one atmosphere,

carrying the Xe from the target in said helium flowing at a low velocity at a rate of about 0.02 liter per minute,

passing said helium gas through a Dry Ice cold trap to remove iodine contaminants therefrom, subsequently passing said helium gas through a liquid nitrogen cold trap to remove Xe therefrom, subsequently passing said helium gas through an oil bubbler and then venting said helium gas to atmosphere, holding the *Xe in said liquid nitrogen trap girl a period of time sufficient for it to decay to References Cited NYO-910-75, September 1968, pp. 47-50, 52, 57, 59, 62, 64, 76-79.

Isotopes and Radiation Techology, vol. 4, No. 3, 1967, pp. 275-280.

0RNL-3 802, 1964, p. 26.

ORNL-3633, 1964, p. 10.

Journal of Nuclear Medicine, vol. 9, No. 6, June 0 1968, p. 349, by Sodd et a1.

BENJAMIN R. PADGETT, Primary Examiner

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