WO1993011871A1

WO1993011871A1 - An apparatus for manufacturing of radioisotope labelled chemicals and pharmaceuticals

Info

Publication number: WO1993011871A1
Application number: PCT/SE1992/000849
Authority: WO
Inventors: Sören Johansson
Original assignee: Johansson Soeren
Priority date: 1991-12-10
Filing date: 1992-12-09
Publication date: 1993-06-24

Abstract

The present invention relates to an apparatus for the manufacturing of radioisotope labelled chemicals and pharmaceuticals, said apparatus comprising a first, disposable module (21-35, 54) supporting all of the components which are at risk to be contaminated when performing the desired process and necessary for performing said process, a second module (36-57) supporting the rest of the components necessary for performing said process, and means (14-17, 45-47) for attaching said two modules to each other in an easily removable way.

Description

An apparatus for manufacturing of radioisotope labelled chemicals and pharmaceuticals.

BACKGROUND OF THE INVENTION The present invention relates to an apparatus for the manufacturing of isotope labelled chemicals intended to be used as radiopharmaceuticals, by chemical reaction involving at least one radioisotope, such as 18F, 11C,

In existing apparatuses a thorough cleaning of the various tubings and vessels of the apparatus involved in the manufacturing process must be made after a production batch before the apparatus can be used for manufacturing an isotope labelled chemical of another kind in order to avoid the risk of cross contamination. Furthermore, after a production run the apparatus is contaminated with radioactive material which means that the cleaning must be left until the radioactive radiation in the remaining process liquids has decayed to safe levels which can take from half an hour to several days or the cleaning must be performed under severe conditions. These operations are time consuming and limit the output performance of known apparatuses.

The present invention provides an apparatus of the aforementioned kind which after a production batch of one type of isotope labelled chemical can be used for the manufacturing of another type of isotope labelled chemical without an intermediate cleaning of the apparatus and in which the problem of remaining radioactive radiation from the apparatus after the use thereof is eliminated. SUMMARY OF THE INVENTION The present invention relates to an apparatus for the manufacturing of radioisotope labelled chemicals and pharmaceuticals, said apparatus comprising a first, disposable module supporting all of the components which are at risk to be contaminated when performing the desired process and necessary for performing said process, a second module supporting the rest of the components necessary for performing said process, and means for attaching said two modules to each other in an easily removable way. With such a construction no cleaning between production batches is necessary and a new production batch can be started immediately after the used diposable module is replaced with a fresh one.

In a preferred embodiment of the invention the means for attaching the first and second modules to each other comprise a displaceable wall of the second module which holds the disposable module against a fixed wall of the second module in the attached state of the first module and the first module comprises tubing for distributing process chemicals from storage containers or the like to reaction vessels supported by the first module, said tubing being flexible tubes disposed between the fixed and the displaceable wall of the second module, the valves necessary for the process in question being constituted by plungers pinching parts of the tubes against the displaceable wall of the second module when activated. By these measures the disposable module can be constructed of cheap components which will make the use of an apparatus according to the present invention feasible also in an economic sense.

BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described in more detail with reference to the accompanying drawings, in which Fig. 1 is a schematic front view of a disposable module according to the invention and stepping motors supported by the second module and cooperating with injection devices in the disposable module. Fig. 2 is a partly sectional side view of the disposable module of Fig. 1 also illustrating some essential parts of the second module.

DESCRIPTION OF THE PREFERRED EMBODIMENT In the upper part of Fig. 1 a number of activating devices 37-42 supported by the second module are shown. In the lower part of Fig. 1 the disposable module of the apparatus of the invention is illustrated in the form of an elongated, rigid strip 21 provided with a row of openings 22, as schematically indicated in this Fig. Some of those openings are surrounded by collars or sleeves 23 downwardly projecting from the strip 21 and preferably being integral with said strip. Injectors 24 are inserted in at least some of those sleeves and fit tightly therein. In their bottom part the sleeves are connected to flexible tubes being part of the system for distributing chemicals to and from reaction vessels supported by the strip 21, such as the hydrolysis chamber 29 mounted in one of the openings 22 in the strip. In another opening 22 in the strip a storage chamber 25 for gas which contains the radioisotope to be treated by the chemical system carried by the strip is inserted. On the top of the storage chamber 25 a Luer connection for a gas hose is provided which for the sake of clarity is not shown on the figure. A separation column 27 is coupled to the sleeve supporting the third injector 24 from the left, as seen in the figure, and arranged beneath this separation column 27 is a branch pipe 28. The two ejectors located farthest to the left in the figure and the storage chamber 25 are by appropriate tubing connected to the branch pipe 28. Hydrolysis chamber 29 is by appropriate tubing connected to the branch pipe 28 and to the two injectors 24 located nearest it. A tube from the hydrolysis chamber leads via an intermediate vessel 30 to an outlet tube 31 for the isotope labelled product produced in the chemical system on the strip. At least some of the injectors supported in the sleeves 23 are connected to containers for storage of the chemicals used for the process in question by suitable tubing, such as the flexible tube 54 connected to the sleeve 23 located farthest to the left in Fig. 1.

As will be understood, the components included in the disposable module will depend on the type of starting material used and the kind of end product desired. Consequently, the various chemical process steps will not be described in detail, since these are not essential to the invention. It is essential to the invention, however, that all reaction vessels, process-liquid containers, gas containers, etc are arranged on a disposable strip 21. In order to ensure a secure affixation of said components to the strip the disposable module with its strip, vessels and tubing may be covered with shrink film material. The film covering will also serve as a sterilization guard.

The injectors 24 serve to suck up chemicals from storage containers and distribute these to the process vessels. Each injector 24 includes a cylindrical container 32 having two ends, the upper end carrying a flange 33 and the lower end ending in a downwardly tapered cone 34. Each injector also includes a stem 35, the lower end of the stem being attached to a piston or a plunger (not shown) which is slidable inside the cylindrical container 32. Mounted on the second module of the apparatus according to the invention are stepping motors 36 in a number corresponding to the number of injectors 24. Each stepping motor 36 has a shaft 37 which is moved linearly in a vertical direction when the stepping motor is activated. A clamping device 38 is mounted on the lower end of each shaft 37. In Fig. 1 one of these clamping devices 38 is shown in cross section. Each clamping device includes a cylindrical block 39 having a substantially vertical blind bore 40 presenting a funnel- like widening 41 in its opening for guiding the upper end of the stem 35 into the bore 40. An optical position sensor 42 functions to detect when said end of the shaft has reached the bottom of the blind bore 40 during downward movement of the stem 37. At the moment when the stem bottoms in the bore 40 a pneumatic cylinder 43

(illustrated in Fig. 2), the shaft 44 of which slides in a radial opening in the block 39, operates to clamp the stem 35 of the corresponding injector firmly in the bore 40. Thereafter the injector stem 35 and consequently also the injector piston (not shown) will move together with the shaft 37 of the stepping motor. This arrangement enables process liquids to be metered very accurately and to be transported through the chemical system.

In Fig. 2 the means for attaching the disposable module and the second module to each other are schematically shown. These means comprise a fixed wall 14 and a displaceable wall 15 of the second module. The walls 14,15 are provided with horizontal flanges 16,17, which are located opposite to each other and extending along the length of the strip 21 of the disposable module. In the attached state of the modules, the displaceable wall 15 presses the strip 21 against the fixed wall 14 as illustrated in Fig. 2. Furthermore, an arm 45 swingable round an axis 46 can be used for ensuring that the strip will not loosen from the grip of the two walls 14,15 due to forces created when the injectors are used for sucking chemicals from before entioned storage containers. However, other solutions in this respect can be foreseen, such as providing the walls 14, 15 with a pair of horizontal flanges, the upper flanges covering outer parts of the strip 21 only in the attached state of the modules. The flanges 16,17 shall project out from the walls 14,15 to such an extent that the strip can rest on outer parts of these flanges in the unattached state of the modules, i.e. when the displaceable wall has been moved to its outer position away from the fixed wall 14. The movement of the displace-able wall 15 is preferably controlled by a pneumatic cylinder (not shown) and it is preferably attached to the fixed wall by a suitable sliding arrangement.

In Fig. 2 a pinch valve in form of a pneumatic cylinder

52 is schematically illustrated. In this figure the shaft

53 of the cylinder 52 is pinching a flexible tube against the movable wall 15 thereby preventing transport of liquid in this tube. The second module comprises several such valves in order to control the transport of process liquids in the chemical system of the disposable module.

Also shown in Fig. 2 are two heating jaws 48 and 49, which can be moved towards and away from the separation column 27 for the purpose of heating the process liquid flowing through said column, the movements of these jaws also being controlled by pneumatic cylinders (not shown) , for example. Each heating jaw 48,49 is moveably mounted in a cylindrical housing 50 and 51, respectively, which housing is fixed to one of walls 14 and 15 of the second module. The front surface of each heating jaw is provided with an elongated groove. The configuration of the respective groove is such that when the grooves are brought together to the position shown in Fig. 2 the grooves will encircle the outer surface of the separation column 27.

Movements of the displaceable wall of the second module, movements of the stepping motors, monitoring of the positions of the injector stems, depression of the injectors into the respective sleeves, and activation of the pinch valves are controlled with the aid of known control electronics mounted in the second module. All of the process stages can be program-controlled, thereby enabling the process to be carried out fully automa- tically from the moment an unused disposable module is attached to the second module of the apparatus.

The aforedescribed preferred and exemplifying embodiment of the invention can be modified and changed in many ways within the scope of the following claims. For example, several disposable modules can be placed sequentially in line to achieve the proper configuration of the necessary equipment for manufacturing a specific chemical product. The transport of liquid media in the system can be achieved with the use of over-pressure or under-pressure.

Claims

1. An apparatus for the manufacturing of radioisotope labelled chemicals and pharmaceuticals, said apparatus comprising a first, disposable module (21-35, 54) , which comprises process liquid-injectors (24) , reaction vessels (29) and tubing for transporting process liquids there¬ between, and a second module (36-53) , which comprises means (36-42) for activating said injectors (24) , the first module being supported by the second module, and means (14-17, 45-47) releasably attaching said first module to said second module.

2. An apparatus according to Claim l, wherein the means releasably attaching said first module to said second module comprise a displaceable wall (15) of the second module which releasably holds the first module against a fixed wall (14) of the second module.

3. An apparatus according to Claim 1 or 2, said second module comprising tubing (54) for supplying process liquid to said injectors (24) , the last-named tubing being disposed between said fixed and displaceable walls (14, 15) of said second module, and a plunger (53) for pinching the last-named tubing against one (15) of said walls thereby to control the flow of process liquid through the last-named tubing.

4. An apparatus according to any one of Claims 1-3, wherein the first module comprises a rigid elongated strip (21) provided with a row of .openings (22) , sleeves (23) projecting from about at least some of said openings and formed integrally with the^* strip (21) , said sleeves (23) forming supports for disposable containers (32) of said first module adapted to be inserted in said sleeves.

5. An apparatus according to any one of Claims 1-4, the first module further comprising a number of injectors (24) each coacting with a linearly movable shaft (37) of a stepping motor (36) mounted on said second module.

6. An apparatus according to any one of Claims 1-5, wherein the first module comprises a reaction vessel in the form of a pipe section connected to a free end of one of the sleeves (23) of said first module, and the second module comprises two heating jaws (48, 49) surrounding said pipe section when said modules are attached to each other.

7. A disposable module for insertion into an apparatus for the preparation of radiopharmaceuticals with a radioisotope as a starting substance, wherein said module comprises an elongated, rigid strip (21) which is provided with a row of openings (22) , sleeves (23) mounted around certain of the openings and projecting out from a main surface of the strip, process liquid- injectors (24) inserted in said sleeves (23) and supported therein, reaction vessels supported by the strip (21) , and tubing for transporting process liquids between said reaction vessels.