WO2002065946A1

WO2002065946A1 - Apparatus for loading a therapeutic agent onto an endovascular device

Info

Publication number: WO2002065946A1
Application number: PCT/CA2002/000240
Authority: WO
Inventors: André LEDUC; Remi Martel; Luc Levesque
Original assignee: Angiogene Inc.
Priority date: 2001-02-23
Filing date: 2002-02-25
Publication date: 2002-08-29

Abstract

An apparatus (100) for loading a therapeutic agent onto an endovascular device (102), comprises a holder (106, 120 and 124) operated by a control unit (140) for carrying the endovascular device (102) to a number of processing stations, such as a dipping station (108), a drying station (110), a rinsing station (112) and a quality control station (114). The control unit operates the holder (106, 120 and 124) for dipping the endovascular device (102) into a solution containing a therapeutic agent for a predetermined period of time. The device (102) is subsequently carried by the holder (106, 120 and 124) to the other stations, where the device (102) is further processed in a sterile environment just before being used.

Description

APPARATUS FOR LOADING A THERAPEUTIC AGENT ONTO AN ENDOVASCULAR DEVICE

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates to an apparatus which automatically alters medical devices used for endovascular procedures prior to use within hospital facilities, whereas the alteration of the medical devices may include a device modifying step, washing, drying and assessment of modification while remaining sterile throughout and following the procedure .

2. Description of the Prior Art Endovascular procedures provide minimally invasive alternatives to standard open vascular surgical operations. A variety of endovascular approaches are available to treat arterial occlusive diseases, aneurysms, dissections, and traumatic injuries. These methods include balloon angioplasty, intravascular stents, stent grafts, atherectomy devices and aneurysm embolization.

The main advantage of endovascular procedures is that the instruments such as wires, catheters, balloons and coils are introduced via a small incision in peripheral arteries and are guided to the target vessels using specialized catheters and wires. Therefore, these procedures minimize side effects related to invasive procedures such as surgery. Examples of endovascular procedures can be summarized below:

Angioplasty is a procedure that uses a high-pressure balloon of a diameter close to that of the intended target vessel. The balloon is introduced into the atherosclerotic vessel via a catheter and guidewire.

By expanding the balloon, the atherosclerotic plaque is disrupted and remodeled into a larger lumen. The desired result is an increased amount of blood flowing through the formerly narrowed area of the vessel . This method is successfully used in coronary arteries, renal arteries and other larger arteries of the body. Stenting is a variation of balloon angioplasty as a stent, which is a wire "cage" of "frame", is deployed at the diseased site of the artery to prevent its elastic recoil following angioplasty. Therefore, the stent will increase the durability of an angioplasty, yet adds little to the complexity or risk to the procedure.

. Atherectomy is a procedure performed to open up the blockages in coronary arteries . The atherectomy device which has a small mechanically driven cutter that shaves the plaque from the inside of the artery is placed in the diseased portion of the vessel. After being shaved from the artery wall, this plaque is stored safely in the tip of the catheter and removed from the body. The desired post procedural result is similar than the angioplasty procedure .

Intravascular ultrasound (IVUS) is a tiny ultrasound probe that is inserted into a vessel to provide a 3 60-degrees view of the vessel. This procedure is sometimes used to document satisfactory results from an angioplasty or stent placement .

Endovascular stent-grafting is a procedure consisting of a balloon-expandable metal stent covered with a dacron graft for the treatment of abdominal aortic aneurysm (AAA) . The stent is introduced through the femoral artery to reach into the aorta. It is then deployed and fixed in position within the aneurysm by balloon expansion of the stent, thus excluding the abdominal aortic aneurysm from circulation.

Endovascular detachable coil treatment of intracranial aneurysms is a procedure used to obliterate the aneurismal sac through the introduction of soft helix shaped platinum coils. These platinum coils are introduced through peripheral vessels and are guided into the aneurismal sac. These flexible coils will fill the aneurysm and hence, prevent its rupture.

The following scenarios are clinical examples in which endovascular devices, such as a platinum coil or a stent mounted onto a balloon, can be rendered radioactive just prior to insertion into a patient for the treatment of intracranial aneurysms or prevention of restenosis, respectively. Restenosis after coronary angioplasty is a major limitation of an effective and safe procedure for the treatment of coronary artery disease. It affects 20 to 40% of patients within 6 months after initial balloon angioplasty. Restenosis after angioplasty is multi-factorial, with proliferative and nonproliferative components. A method to prevent restenosis is to expose the coronary artery to a radioactive stent. Since radiation possesses a natural physical decay, inventory management of radioactive stents of various lengths and diameters would be logistically difficult. Therefore, a method has been developed to render the stents radioactive by simply dipping them into a radioactive solution. For example, stents coated with phosphorylcholine (PC) or other polymers, which is the main phospholipid of the outside surface of red cell membranes, have been developed to permit loading of a variety of drugs or therapeutic agents and to release them in a controlled manner into the arterial wall. Loading of the stent with a 32P- oligoucleotide has been developed. So far, such 32P- oligoucleotide loaded stents have been manually prepared by skilled technicians prior to the surgery. More specifically, each drug loaded stent is individually and manually prepared by dipping a PC coated stent into a 32P-oligonucleotide solution which is formulated into a concentrated solution for a predetermined amount of time, drying the stent in order to remove excess solution from the stent and finally measuring the radioactive level of the stent .

In addition of requiring qualified personnel, the above-described method does not provide a standardized and repeatable procedure, as it depends, at least in part, on the technician performing the loading operation. Furthermore, in some cases, the manipulation procedures may represent a potential hazard to the technician.

It would therefore be highly beneficial to have the above-described steps performed in a simple and efficient automated fashion while the stent and balloon remain sterile through the entire process. It would also be beneficial to be able to load the drug onto the endovascular device in the operation room just prior to the surgery with a minimum of effort and skill, preferably without requiring human intervention. In this way, the surgeon himself could perform the drug loading operation.

Endovascular treatment of intracranial aneurysms is frequently followed by rebleeding of the treated aneurysm. Control angiographies of patients reveal significant recurrence in 20% of cases, whereas 50% of the patients presented incomplete obliteration of their aneurysms, a risk of future recurrence. A method to prevent rebleeding of the aneurysm is to expose the aneurysm to a local source of radiation which is delivered through radioactive coils. Since there exists an impressive amount of different types of coils, inventory management of radioactive coils which possess a natural physical decay would provide to be tedious. Therefore, a method has been developed to render the coils radioactive within the hospital facilities prior to introduction in the patient. This method consists of dipping a coil into a heated solution of a 32P-oligonucleotide for a determined amount of time. The coil is then placed in a washing solution to remove weakly bound 32P-oligonucleotide then dried to remove the washing solution. The last step of the process is a radioactive measurement step in which the levels of radioactivity is evaluated. As for the radioactive stent, skilled personnel perform these steps manually. It would be desirable to perform these steps in a simple and efficient automated fashion while the coil remain sterile through the entire process.

As can be appreciated from the foregoing, it may sometimes be of use to alter endovascular devices, such catheters, balloons, guidewires, stents and coils just prior to use. Therefore, it would be desirable to have an apparatus that can alter endovascular devices such as loading of therapeutic compounds in a clinical setting. SUMMARY OF THE INVENTION

It is therefore an aim of the present invention to simplify the loading of a therapeutic agent onto an endovascular device. It is also an aim of the present invention to reduce the human intervention in the loading of a therapeutic agent onto an endovascular device.

It is a further aim of the present invention to provide a simple and efficient method of loading a therapeutic agent onto an endovascular device with a minimum of effort and^' skill.

It is a still further aim of the present invention to provide an apparatus for controlling the loading of a therapeutic agent onto an endovascular device.

It is still a further aim of the present invention to permit loading of a radiation-emitting molecule onto an endovascular device under a lower contact risk of radiation. It is still a further aim of the present invention to provide for the automatization of a loading process of a therapeutic agent onto an endovascular device .

The present invention generally relates to an apparatus for altering endovascular devices in a clinic just prior to use. The apparatus is a unit that performs certain tasks, which are not all necessary in every application. The tasks may include a modifying step, a washing step, a drying step and a quality control step.

The modifying step can comprise, but not limited to, loading of therapeutic compounds, inducing a change of temperature, top coating the device with biologically inert or active compounds or inducing a magnetic field. The washing step can comprise, but not limited to, dipping in a washing solution or application of compressed air to reduce amount of weakly attached compounds onto the device. The drying step may comprise passing the endovascular device through a stream of air or; passage through an absorbent material. The quality control step is a method to determine whether the endovascular device has been properly modified. Methods to assess proper modification of the device would be radioactivity assessment, mass or ultraviolet or visible spectroscopy, circular dicroism, refraction index or temperature melting points.

According to a preferred embodiment of the present invention, the apparatus would be used for the application of a radioactive 32P- oligonucleotide . In one application, a catheter- balloon on which a stent is placed would be inserted in the apparatus, whereas the balloon/stent would be dipped in the 32P-oligonucleotide solution for a predetermined amount of time under agitation. The balloon/stent combination would then be passed through an air dryer for a predetermined amount of time then finally inserted into the radioactive counter which forms an integral part of the apparatus to determine whether loading of the 32P- oligonucleotide is adequate. In another application, a platinum coil attached to a support would be dipped in a heated 32P-oligonucleotide solution at 65°C for a determined amount of time. The coil is then transferred into a washing solution such as PBS under agitation to remove weakly bound 32P- oligonucleotide . Thereafter, the coil is dried by passage through a stream of air. Finally, the coil is inserted into the integrated radioactive counter to assess whether loading of the 32P-oligonucleotide is adequate.

In accordance with a general aspect of the present invention, there is provided an apparatus for loading a therapeutic agent onto an endovascular device, comprising a first station containing a solution with a therapeutic agent, a second station for performing at least one of a rinsing, a drying and a quality control operation, a holder for holding and carrying the endovascular device from said first station to said second station, and a control unit controlling the operation of said holder.

In accordance with a further general aspect of the present invention, there is provided a method of loading a drug onto an endovascular device, comprising the steps of: installing the endovascular device on a holder operated by a control unit programmed to provide adequate timing movements of the holder in order to permit loading of a desired amount of drug on the endovascular device depending on the particular endovascular device to be processed, using the holder to dip the endovascular device into a solution containing a therapeutic agent for a predetermined amount of time under agitation, operating the holder to displace the endovascular device to a post-loading station, and performing at least one of a quality control, a drying and a rinsing operation onto the endovascular device at said post- loading station. Preferred therapeutic drugs which may be delivered by the present invention belong to the following subgroups: anti-proliferative agents to prevent uncontrolled cellular proliferation and tissue growth, anti-inflammatory agents to prevent inflammation, anti-thrombotic drugs to prevent or control formation of thrombus or thrombolytics and other bioactive agents which regulate uncontrolled cellular proliferation, tissue growth or promotes healing of the tissue. Examples of therapeutic compounds which can be used in the present invention include, but are not limited to anti-neoplastic drugs which are subdivided in the following subclasses: alkylating agents (ex. , cisplatin, melphalan) , antimetabolites (ex., methotraxate, 5-fluorouracil) , antibiotics (ex. , actinomycin D, bleomycin) , mitotic inhibitors (ex., vincristine, vinblastine, paclitaxel, colchicine) , hormones (ex. , prednisone, tamoxifen) . Other drugs can be used such as anti-coagulants (ex. , heparin, coumarin compounds) fibrinolytic agents (ex. , streptokinase, urokinase) , non-sterioidal anti- inflammatory drugs (NSAIDs) (ex. , ibuprofen, naproxen) , steroidal anti-inflammatory drugs (ex. prednisone, dexamethasone) , sodium channel blockers (for example, lidocaine, procainamide) and calcium channel blockers (for example, nifedipine and verapamil) , nitric oxide donors (ex. , nitroglycerin) , alpha-adrenoceptor blockers (ex. , phentolamine, prazosin) , genetic material containing DNA and RNA fragments, complete expression genes, anti-bodies, prostaglandins, leukotrienes, elastin, collagen, integrins, growth factors, radioisotopes and radioactive molecules.

Therapeutic agents may be administered in accordance with the present invention either alone or in combination with other therapeutic agents as a mixture of these compounds and can contain pharmaceutically acceptable carriers and/or additional inert ingredients. BRIEF DESCRIPTION OF THE DRAWINGS

Having thus generally described the nature of the invention, reference will now be made to the accompanying drawings, showing by way of illustration a preferred embodiment thereof, and in which:

Fig. 1 is a partial schematic representation of a catheter attached to a support wire;

Fig. 2 is a schematic representation of a control device adapted to regulate the movement of the coil through a disposable cassette in accordance with a first embodiment of the present invention;

Fig. 3 is a schematic representation of the cassette in which the coil is loaded with a radioactive solution; Fig. 4 is a schematic perspective view of an apparatus for loading a therapeutic agent onto an endovascular device in accordance with a second embodiment of the present invention;

Fig. 5 is a schematic partly exploded view of the apparatus of Fig. 4;

Fig. 6 is a schematic exploded view of a turntable forming part of the device of Fig. 4;

Fig. 7 is a rear schematic perspective view of the apparatus; and Fig. 8 is a diagram of the control unit of the apparatus . DESCRIPTION OF THE PREFERRED EMBODIMENTS

Now referring to the drawings, and more particularly to Figs. 1 to 3 , a system suited for loading a therapeutic agent onto an endovascular device, such as catheters, balloons, guidewires, stents and coils, and embodying the elements of the present invention will be described. As will be seen hereinafter, the loading system advantageously provides for the automatization of the loading process of therapeutic agents or compounds onto an endovascular device, such as the one depicted by numeral 10 in Fig. 1. According to one embodiment of the present invention, the apparatus is used to load a radioactive molecule, such as ³²P- oligonucleotide, on the surface of the endovascular device 10 to inhibit recanalization and stimulate neointima formation within an aneurysm and at the neck of treated aneurysm. However, it is understood that the endovascular device 10 is not restricted to this use as it could also be used to close any body lumen, such as vascular lumen or others. The endovascular device 10 illustrated in

Fig. 1 is of standard construction and generally comprises a detachable filling coil 12 extending from a push wire 16.

As shown in Figs . 2 and 3 , the loading system generally comprises a control device D adapted to receive one or more disposable cassettes C.

As shown in Fig. 3, each cassette preferably comprises three chambers: an immobilization chamber 17, a washing chamber 18 and a drying chamber 19. The control device D is composed of, but not limited to, a cassette holder 26, a movable arm system 27 for holding and carrying the coil 12 from one chamber to another, a cell type selector 28, a time display device 29 and a start button 30. The control device D can also be equipped with a system to measure the radioactivity retained onto the endovascular device 10. The control device D will accept several types of disposable cassette which dictates the sequence of events adapted for a particular type of coil. The coil 12 is first inserted into the movable arm 27 then dipped into a radioactive solution, such as a 32P-oligonucleotide solution 21, contained in the immobilization chamber 17. After a predetermined amount of time (that depends on the radioactivity desired on the coil) , the control device D through the arm 27 will move the coil 12 automatically into the washing chamber 18. The washing chamber 18 is built around a turbine wheel mechanism 24, which allows the wash solution to circulate within the entire chamber. The wheel mechanism 24 is driven by a drive source (not shown) forming part of the control device D. The drying chamber 19 is composed of an absorption material in which the coil 12 will be dried before being released from the disposable cassette C through an exit port 24. After having been released, the coil 12 is ready to be used in the clinic. When the process is completed, the disposable cassette C, which does not generate any external liquid radioactivity, is simply disposed in the radioactive waste. One disposable cassette C is preferably used per coil .

Figs. 4 to 8 illustrates a second embodiment of the present invention. More specifically, Fig. 4 illustrates an apparatus 100 suited for use in the preparation of a drug loaded endovascular device 102 detachably mounted on a support, such as a catheter 104.

The apparatus 100 generally comprises a turn-table 106 and a four stations, namely a loading station 108, a drying station 110, a rinsing station 112 and a quality control station 114, uniformly distributed about the turn-table 102. According to a preferred embodiment of the present invention, the stations are placed about the turntable 106 on an arc of circle and there is 45 degrees between each station.

The turntable 106 and the stations 108, 110, 112 and 114 are preferably housed in a shielding box (not shown) .

As shown in Fig.6, the turntable 106 is mounted on an axle 107 drivingly connected to a rotary motor and gear drive arrangement (not shown) housed in a box 128. As shown in Fig. 5, the turntable 106 is connected to a linear actuator 136 by means of an anchor 109 projecting laterally outwardly from a side of the box 128 for engagement with an anchor-receiving portion 111 of the actuator 136. The actuator 136 is housed in an upstanding housing section 116 extending vertically from a base section 118. The stations 108, 110, 112 and 114 are preferably located in the base section 118 of the apparatus 100.

The turntable 102 is provided on a top surface thereof with a number of circumferentially spaced-apart supports 120 adapted to receive and releasably retain the catheter 104. Each support 120 defines a number of radially spaced-apart grooves (not shown) for receiving a section of the catheter sheath 122 in a snap fit manner. In this way the catheter 104 can be readily manually installed in a coil configuration on the top surface of the turntable 106.

A guide or nozzle 124 is mounted at the periphery of the turntable 106 to allow the endovascular device 102 to hang out of the turntable 106, thereby permitting the device 102 to be sequentially processed by the stations 108, 110, 112 and 114 once the catheter 104 has been properly installed on the table 106. The guide 124 is provided in the form of a small plate defining a curved groove 126 on one face thereof for receiving the endovascular device 102. It is understood that more than one guide could be installed at different locations along the circumference of the table 106 in order to allow more than one endovascular device to be processed at a same time. The endovascular device support (e.g. the catheter) could be stacked on the table 106 with the endovascular devices hanging out of the table 106.

The motor and gear arrangement provided underneath the turntable 106 is operable to drive the axle 107 and, thus, the table 106 in rotation, as schematically depicted by arrows 130 in Fig. 4.

The linear actuator 136 is provided to raise and lower the turntable 106, as represented by arrow 138 in Fig. 4. A control unit 140 governs the operation of the rotary motor and of the linear actuator 136. As shown in Fig. 7, RS232 entry ports 137 are provided in the back face of the upstanding housing section 116 for allowing the rotary motor and the linear actuator 136 to • be connected to the control unit 140. As illustrated in Fig. 8, the control unit 140 is operatively connected to two sets of optical detectors 142 an 144, one for the rotary motor 128 and one for the linear actuator 136. The first set of optical detectors 142 includes four optical detectors mounted on the top surface of the box 128. Each detector of the first set 142 corresponds to the position of a particular station. The positioning of the endovascular device 102 at a given station is validated when the associated detector detects the passage of a position marker provided in the form of a pin 146 extending downwardly from the undersurface of the turntable 106. When one of the optical detector of the first set 142 detects the passage of the pin 146, a signal is send to the control unit 140 which will in turn send a control command to the motor 128 in order to automatically immobilize the turn-table 106 in position. In this way the endovascular device 102 can be transported from one station to the next. Likewise, each optical detector of the second set 144 is used in conjunction with a position marker 145 to immobilize the turntable 106 at various predetermined heights. As^" shown in Fig. 5, the position marker 145 extends laterally outwardly from the box 128 and the second set of detectors 144 is installed on one side of the actuator 136.

As shown in Fig. 7, a power supply entry 147 and an on/off switch 149 are provided on the back side of the upstanding housing section 116 for allowing the motor and the actuator to be powered and shut down.

According to one embodiment of the present invention, the loading station 108 comprises a container 148 holding a solution containing a radioactive molecule. The container 148 is deep enough to allow a complete immersion of the device 102 into the radioactive solution. The container 148 is a centrifuge tube inserted into an acrylic container to minimize irradiation. The radioactive agent could also be loaded onto the device by an electrodeposition technique.

The drying station 110 comprises an air dryer compartment equipped with a blower 150 (Fig. 7) adapted to direct air through a 0,22 μm filter for drying the device 102 in a sterile environment. The control unit 140 controls the operation of the blower 150.

The rinsing station 112 comprises a compartment 154 containing a rinsing solution, such as water or phosphate buffered saline (PBS) , to remove excess solution loaded onto the endovascular device 102.

The quality control station 114 comprises a conventional dosimetric apparatus 156, such as the ones manufactured by Capintec, NJ, USA, for quantifying the radioactivity of the device 102.

In operation, the device support system (the catheter and its sheath) is put in place on the turntable 106 allowing the device 102 (i.e. the stent or the coil) to hang adequately out of the table 106 to be processed by the stations 108, 110, 112 and 114. The control unit 140 will then allow the turntable 106 to position itself so that the hanging part of the catheter 104 with the endovascular device 102 will be directly above the container 148 with the prepared radioactive drug. The control unit 140 will then have the table 106 move up and down at a specific speed for a definite period of time so that the loading of the drug can be achieved onto the device 102 by dipping the device 102 in the solution under agitation. The time required to achieve loading is based on the amount of radioactivity desired. It is pointed out that the solution can be pre-heated and maintained at a desired temperature during the loading process. After the loading of the drug, the table 106 rotates to bring the device 102 to the rinsing station 112, wherein the device 102 is soaked in a washing solution to remove weakly bound 32P-oligonucleotide . After the rinsing step, the turn-table 106 is rotated to move the device 102 to the drying station 110, wherein the device 102 is exposed to a continuous flow of air blown through the filter in order to remove the washing solution. Once the drying step has been completed, the device 102 is moved to the quality control station 114 where the radioactivity of the device 102 is quantified. Thereafter, the turntable 106 is rotated to a position whereat the device 102 and its support 104 can be manually removed from the table 106. Depending on the length and the cross- section of the device to be processed, the control unit will computes: a) The quantity of drug substance and drug product to be sampled prepared and mixed; b) The duration and timing of up and down and rotating movements of the turn-table 106 to direct the device 102 to different stations; and c) The duration of drug loading steps into different stations (sampling, drying and measurement) . In summary, the apparatus 100 is an automated quality control system helping to perform drug loading under lower contact risk of radiation. By the use of an automated quality control system, the drug loading is always performed under the same conditions and with the same movement, speed and duration. The apparatus 100 advantageously allows preparation of a . radioactively coated endovascular device to be used just moments after its loading with the radioactive molecule. It is understood that the stations could be modified to impart other treatments to the endovascular devices. For instance, the loading station could be used to coat the device with biologically inert compounds or induce a magnetic field. Also, mass or ultra-violet or visible spectroscopy, circular dicroism, refraction index or temperature melting point tests could be performed at the quality control station:

While the invention has been described with particular reference to the illustrated embodiment, it will be understood that numerous modifications thereto will appear to those skilled in the art. Accordingly, the above description and accompanying drawings should be taken as illustrative of the invention and not in a limiting sense.

Claims

CLAIMS :

1. An apparatus for loading a therapeutic agent onto an endovascular device, comprising a first station containing a solution with a therapeutic agent, a second station for performing at least one of a rinsing, a drying and a quality control operation, a holder for holding and carrying the endovascular device from said first station to said second station, and a control unit controlling the operation of said holder.

2. An apparatus as defined in claim 1, wherein said holder is movable along two independent directions, the holder being movable along a first direction to displace the endovascular device between the first and second stations, and a second direction to dip the endovascular device in the solution when at said first station.

3. An apparatus as defined in claim 1, wherein said holder includes a turntable linearly movable by an actuator.

4. An apparatus as defined in claim 3, wherein said first and second stations are located about said turn-table, and wherein said holder further includes a guide for allowing the endovascular device to hang out from the turn-table in order to be processed by the first and second stations.

5. An apparatus as defined in claim 1, wherein said second station is a drying station, and wherein said apparatus further includes third and fourth stations for respectively rinsing and controlling the quality of the processed endovascular device.

6. An apparatus as defined in claim 3, wherein said control unit includes a first set of sensors adapted to detect the passage of a first position maker on said turn-table for allowing the turn-table to be immobilize when the endovascular device has reached one of the stations.

7. An apparatus as defined in claim 3 or 6 , wherein said control unit includes a second set ^'of sensors adapted to detect the passage of a second position marker for allowing the turn-table to be lowered and raised at different predetermined elevations .

8. An apparatus as defined in claim 2, wherein said control unit is adapted to cause said holder to be reciprocated along said second direction so as to dip the endovascular device in the solution containing the therapeutic agent for a predetermined period of time under agitation.

9. An apparatus as defined in claim 1, wherein the therapeutic agent is a radioactive molecule, and wherein said first station comprises a radioactively shielded container and a centrifugal tube housed within said container.

10. An apparatus as defined in claim 1, wherein said second station includes a filter through which air is blown by a blower to remove excess solution on the endovascular device.

11. An apparatus as defined in claim 1, wherein said second station includes a compartment containing a rinsing solution to remove excess solution loaded onto the endovascular device.

12. An apparatus as defined in claim 1, wherein said solution is radioactive, and wherein said second station comprises a dosimetric apparatus for quantifying the radioactivity of the endovascular device .

13. An apparatus as defined in claim 1, wherein said first and second stations are provided in a cassette adapted to be removably loaded into a control device .

14. An apparatus as defined in claim 13, wherein said holder includes a movable arm forming part of said control device for moving the endovascular device from said first station to said second station once the cassette has been loaded into the control device.

15. An apparatus as defined in claim 13, wherein said cassette defines an immobilization chamber containing a radioactive solution and adapted to receive the endovascular device, a rinsing chamber for rinsing excess of free radioactive solution off the endovascular device, and a drying chamber for drying the endovascular device.

16. A radioactivity slow-releasing device as prepared with the apparatus of claims 1 to 15.

17. A method of loading a therapeutic agent onto an endovascular device, comprising the steps of: installing the endovascular device on a holder operated by a control unit programmed to provide adequate timing movements of the holder in order to permit loading of a desired amount of drug on the endovascular device depending on the particular endovascular device to be processed, using the holder to dip the endovascular device into a solution containing a therapeutic agent for a predetermined amount of time under agitation, operating the holder to displace the endovascular device to a post-loading station, and performing at least one of a quality • control, a drying and a rinsing operation onto the endovascular device at said post -loading station.