The present invention relates to a device and an applicator suitable for use in episcleral plaque brachytherapy. Particularly, the applicator is usable to deliver a dose of radiation to a portion of the eye globe for brachytherapy of ocular tumours. Intraocular melanomas are tumours that grow inside the eye. While for large intraocular melanomas, the only reasonable treatment option is a removal of the eye, small or medium melanomas can be treated by a treatment known as plaque brachytherapy. Plaque

brachytherapy is a special form of radiation therapy. The plaque, which is a small generally metallic object containing radioisotopes, e.g., radioactive seeds, is surgically implanted on the exterior surface of the eye. More specifically, the plaque is sutured to the outside wall of the eye, i.e., the sclera, proximate the intraocular melanoma located therein. The radiation of the radioisotope penetrates the sclera and encounters the intraocular melanoma. The plaque generally remains on the eye until the intraocular melanoma has received a therapeutic dosage of radiation and after that is surgically removed. Plaque brachytherapy delivers a highly concentrated radiation dose to the tumour. The Collaborative Ocular Melanoma Study

(COMS) chose iodine- 125 ophthalmic plaque radiation therapy using iodine- 125 seeds to treat medium-sized choroidal melanoma. In Europe, ruthenium- 106 is available for the treatment of choroidal melanoma with a tumour height to about 7 mm. However, the limiting factor in the treatment of intraocular tumours with ruthenium- 106 is the size of tumours.

Ru-106 eye applicators are commercially available, for example at Eckert & Ziegler Bebig, Germany. The applicators are available in different types, to provide a match to the individual tumour size and location. They are spherically shaped, with a radius of 12 mm to 14 mm, and have eyelets to be sutured to the sclera. Also, COMS eye applicators for 1-125 ophthalmic tumour treatment are commercially available at Eckert & Ziegler Bebig, Germany. COMS eye applicators are assembled of a gold plaque shell combined with a silicon insert containing iodine- 125 seeds. However, particularly COMS eye applicators having a thickness of 2 to 3 mm are difficult to attach to the eye and cause pressure to the eye and discomfort to the patient.

US 2009/0156881 Al discloses a device suitable for treating an eye that includes a housing and a plurality of fins. At least a portion of the fins is configured such that radiation emitted from one or more radiation seeds positioned in the cavity of the housing is substantially directed toward a centre portion of the eye during use. However, design and size of the plaque shells need to be improved. Thus, there is an ongoing demand for innovative devices. Therefore, the object underlying the present invention was to provide a device usable in brachytherapy of the eye.

The problem is solved by a device suitable for housing one or more radiation sources for applying radiation to a target volume on or within the eye, comprising a housing, the housing comprising an inner calotte, and a rim coupled to the perimeter of the inner calotte, and an outer calotte, wherein the thickness of the rim defines a cavity between the inner calotte and the outer calotte, which is configured to accept one or more radiation sources, and wherein the housing comprises one or more fastening elements by means of which the outer calotte is fastened releasable to the inner calotte and/or to the rim.

The device is usable as a bi-nuclide applicator containing two radioactive nuclides, for example 1-125 and Ru-106. This allows a combinational therapy of ocular melanoma taking advantage of using both nuclides in one applicator. The device is usable for ocular melanoma up to a tumour height to about 10 mm. This allows for an extended application range than that of standard Ru-106 applicators. Further, potential damage to surrounding tissues caused by radiation is reduced compared to standard 1-125 applicators.

The cavity between the inner calotte and the outer calotte, which is configured to accept the radiation sources, allows for the placing of multiple or different radiation sources in a housing of advantageously thin design. Such design facilitates to sew the device to the eye, particularly to the rear of the eyeball and under the eye muscles. This has an advantage especially compared to usual 1-125 applicators, which have a thickness of about 2 to 3 mm. Further, applicators of low thickness exert lesser pressure to the eyeball, which is very inconvenient for the patient and causes discomfort and pain.

The shape of the inner calotte substantially determines the shape of the device. As used herein, the term "calotte" refers to a spherical cap. As used herein, the term "inner" calotte refers to the one of the calottes, which will come in contact with the eye, when the device is attached to an eye. The inner calotte has an inner surface, which is concave, that defines a volume. The concave surface of the inner calotte defines a cavity that preferably corresponds approximately to the curvature of the outer surface of the eye-ball. Such, the device is suitable for housing radiation sources for applying radiation to a target volume on or within the eye. The device is usable as a plaque shell. The radius of curvature of the inner calotte may vary. The radius of curvature may be in the range of > 9 mm to < 15 mm, in the range of > 10 mm to < 14 mm, or in the range of > 11.5 mm to < 12.5 mm. Suitably, the diameter is larger than the largest basal diameter of the ocular tumour to be treated.

A rim is coupled to the inner calotte. Coupling of the rim to the inner calotte can be provided by welding, soldering, gluing or by screws or retainers. The rim particularly can be welded to the perimeter of the inner calotte.

The outer calotte can be fastened releasable to the inner calotte and/or to the rim by means of one or more fastening elements. The releasable fastening provides that radiation sources can be replaced such that the device is re-usable for different radiation sources and tumour treatments. Any suitable form of releasable fastening means may be utilised. Suitable fastening elements are selected from the group of spring locks, locking pins, and screws.

The outer calotte may be screw-mountable. Suitable bore holes can be provided in the rim or in the inner calotte, or by both, the rim and the inner calotte. In embodiments, the rim comprises one or more bores, such as thread holes, and the outer calotte is screw-mountable to the rim. The rim for example can comprise two, three or four bores. Alternatively, the outer calotte may be screw-mountable to the inner calotte by means of a single screw, which can be fastened by means of centered bore holes in the inner and outer calotte.

An embodiment can provide a device suitable for housing a radiation source for applying radiation to a target volume on or within the eye, comprising a housing, the housing comprising an inner calotte, and a rim welded to the perimeter of the inner calotte, wherein the rim comprises one or more thread holes, and an outer calotte, wherein the outer calotte is screw-mountable to the rim, and wherein the thickness (T) of the rim defines a cavity between the inner calotte and the outer calotte, which is configured to accept one or more radiation sources. In embodiments, the material of the inner calotte, the outer calotte and/or the rim can be titanium. Titanium is a very solid material. Sufficient stability can be provided by a slight wall thickness of the calottes. In parallel, pure titanium is sufficient ductile to allow a manufacture of the calottes by deep-drawing. Further, titanium is biocompatible and can be implanted. Unalloyed Titanium for surgical implant applications is commercially available having a certification of the American Society for Testing and Materials (ASTM F76-06). Further, when the concave surface of the inner calotte is made from a continuous titanium film, such surface is very smooth and can be slid very easily into position over the eyeball. In an embodiment, the inner calotte, the outer calotte and the rim are made of titanium. This embodiment provides a re-usable titanium housing.

Titanium can provide very thin but sufficient stable calottes. In certain embodiments, the inner calotte can have a wall thickness in the range of > 20 μιη to < 100 μιη, in the range of > 40 μιη to < 60 μιη, or in the range of > 45 μιη to < 55 μιη. The inner calotte may have a wall thickness of about 50 μιη. In further embodiments, the outer calotte can have a wall thickness in the range of > 25 μιη to < 1 mm, in the range of > 50 μιη to < 250 μιη, or in the range of > 50 μιη to < 100 μιη. A slight wall thickness of the titanium calottes does not contribute markedly to the total thickness of the housing. Advantageously, this allows that substantially the total thickness of the housing can be occupied by a radiation source.

Between the inner calotte and the outer calotte the thickness of the rim defines a cavity, which is configured to accept the radiation sources. The thickness of the rim corresponds to the distance between the inner calotte and the outer calotte. Thus, the rim can have the function of a distance element.

In embodiments, the thickness (T) of the rim can be in the range of > 0.2 mm to < 3.5 mm, in the range of > 0.5 mm to < 2 mm, or in the range of > 0.8 mm to < 1.4 mm. The thickness (T) of the rim may be in the range of > 1 mm to < 1.1 mm. A distance in the range of > 1 mm to < 1.1 mm between inner and outer calotte allows for inserting a standard Ru-106 applicator in the cavity. Except for the titanium calottes, the thickness (T) of the rim corresponds to the overall thickness of the housing. The advantage of a low thickness of the device is particularly obvious compared to standard COMS eye applicators.

In embodiments, the height (H) of the rim can be in the range of > 0.1 mm to < 3.5 mm, in the range of > 0.3 mm to < 2.5 mm, or in the range of > 0.5 mm to < 2 mm. The height of the rim provides stability to the housing. Additional or alternative structures for enhancement of stability can be provided in the housing, such as honeycomb structures. Honeycomb structures can be positioned on the inner or the outer calotte extending into the cavity. The honeycomb structures can span the distance between the calottes, thereby stabilising the cavity. This is particularly advantageous in embodiments when the cavity does not contain a standard Ru-106 applicator, which otherwise would fill and further stabilise the cavity, but other radiation sources. In embodiments, which provide honeycomb structures between the calottes, the height of the rim can be in the range of > 0.1 mm to < 2 mm.

The rim for example can be turned out from a titanium rod. A height in the range of > 1 mm to < 3.5 mm can provide a base body of the rim, which can provide structures for attaching the outer calotte and/or housing radiation sources. The rim can comprise one or more thread holes, for example two, three or four thread holes, for screw mounting the outer calotte to the rim. The thread holes can be arranged symmetrically, for example in opposing positions on the rim or in regular distance.

In embodiments, the rim can comprise one or more recesses for housing radiation sources, such as 1-125 seeds. The recesses can have a form adapted to house the radiation sources. For example, the recesses can have a shape configured for housing standard 1-125 seeds. This allows that the seeds may be securely fixed in the recess without use of fixatives. Providing recesses for radiation sources such as 1-125 seeds in the rim can have the effect that the seeds are arranged in a circular form in the housing. In one embodiment, the entire ring may comprise recesses.

In embodiments, the rim can comprise one or more thread holes and one or more recesses. For example, the rim can comprise four thread holes arranged at about 90 degrees to each other on the rim, and positioned between the thread holes one, two or three recesses depending on the diameter of the housing. A housing having a diameter of the outer calotte of about 24 mm, about 12 recesses for standard 1-125 seeds can be provided on the circumference of the rim.

The housing may comprise beam shaping and shielding elements for shaping the radiation of or shielding the radiation from the one or more radiation sources, particularly the 1-125 seeds. Shielding elements can reduce the radiation exposure of the surrounding tissue and organs on the back of the device. Beam shaping elements can concentrate the radiation to the tumour peak and reduce radiation exposure of healthy tissue in the eye.

The housing may comprise a layer of a shielding material. Particularly, the housing may comprise a layer of shielding material that substantially blocks radiation emitted from 1-125 seeds positioned in recesses of the rim. Such a layer of a shielding material can be positioned at the level of the recesses for holding the 1-125 seeds in the housing. For example, a layer of shielding metal may be positioned at least partially around the 1-125 seeds.

In embodiments, at least a portion of the surface of the one or more recesses can comprise a layer of a shielding metal in the direction of the rim and the outer calotte. The shielding layer may substantially cover the entire surface of the one or more recesses in the direction of the rim and the outer calotte, which can shield the surrounding tissue and organs on the back of the device. For example a gold foil can be cut to size and affixed in the recess using medical silicone. Alternatively, at least a portion of the concave surface of the outer calotte abutting on the rim and a portion of the surface of the rim facing the cavity can comprise a layer of a shielding metal. The shielding material can be gold. Gold shielding effectively blocks radiation emitted from the seeds and prevents excessive irradiation of tissues in the head such as eye and brain structures. Already a thin layer of gold will prevent other organs from being exposed to significant amounts of inadvertent radiation emitted from the seeds. The gold layer forming the shielding layer can have a thickness is in the range of > 20 μιη to < 200 μιη, in the range of > 30 μιη to < 150 μιη, or in the range of > 50 μιη to < 100 μιη. For example, a gold layer having a thickness of about 50 μιη can reduce 1-125 radiation intensity of a standard 1-125 seed to about 2 % of the original intensity. A gold layer having a thickness of about 100 μιη can reduce 1-125 radiation intensity to less than about 1 % of the original intensity. The housing may comprise a collimator structure for forming the radiation field. A collimator can be provided by a layer of gold. A collimator can be provided for shaping the radiation emitted from the one or more radiation sources, such as 1-125 seeds. In embodiments, at least a portion of the surface of the one or more recesses in the direction of the eye can comprise a gold layer forming a collimator for the radiation of the 1-125 seeds in the direction of the tumour. Alternatively, at least a portion of the convex surface of the inner calotte abutting on the rim can comprise a gold layer forming a collimator for the radiation of the 1-125 seeds.

Referring to the 1-125 seeds, the device may comprise a collimator for forming the radiation field in the direction of the eye and a shielding layer for blocking the backward radiation. For providing shielding and collimator function, the 1-125 seed may substantially be covered by a gold layer only leaving an aperture, which can have the form of a slit along the length of the seed, in the gold cover for radiation emission. The slit can be directed towards the eyeball. Further, a shielding foil can be provided for partially blocking the radiation emitted from the Ru-106 applicator. In an embodiment, at least a portion of the surface of the convex surface of the inner calotte in the direction of eye comprises a gold layer forming a shielding for the radiation of a Ru-106 applicator. Referring to the Ru-106 applicator, areas of the eye may be shielded from the radiation.

The gold layer forming the collimator or the shielding can have a thickness in the range of > 20 μιη to < 300 μιη, in the range of > 30 μιη to < 150 μιη, or in the range of > 50 μιη to < 100 μιη.

The housing further may comprise a layer of molybdenum or zirconium metal. Molybdenum or zirconium layers can generate X-ray fluorescence. Molybdenum or zirconium layers can be provided at the level of the 1-125 seeds or the recesses for holding the 1-125 seeds in the housing. The layer of molybdenum or zirconium preferably is located between the 1-125 seeds and the gold layer. The molybdenum or zirconium layer may be provided between the 1-125 seeds and a gold layer in form of a complete shell around the seed.

The housing can comprise a molybdenum or zirconium layer in at least that portion of the surface of the one or more recesses not comprising a gold layer forming a collimator for the radiation of the 1-125 seeds in the direction of the inner calotte, or in at least that portion of the convex surface of the inner calotte abutting on the rim and not comprising a gold layer forming a collimator, or substantially the entire surface of the one or more recesses can comprise a molybdenum or zirconium layer. The device may be sutured to the sclera by way of one or more suture eyelets. Hence, the device can comprise a plurality of suture eyelets. The suture eyelets may be coupled to the rim, particularly to the peripheral edge of the rim. The suture eyelets permit the device to be affixed or sutured to an eye. Each suture eyelet may include a hole sized to accept a standard suture used to the placement of ophthalmic applicators. The eyelets for suturing the device to the sclera may also function as a shim for the screws, which attach the outer calotte to the rim.

The device can comprise one or more light-emitting diodes. Light-emitting diodes can tag the position of the device and facilitate the localisation of the device beneath a tumour via diode- light transillumination through the lens. This allows for a reference between a tumour and the position of an applicator. Suitable light-emitting diodes are for example Lumex, SML- LX0402SIC-TR diodes, available at Palatine, USA. Diode lights can be attached to the rim with their lens flush with the episcleral edge. The device can comprise one or more additional eyelets for housing the light-emitting diodes. For example, the light-emitting diodes can be housed in eyelets coupled to the rim. Alternatively, the light-emitting diodes may be housed in the recesses, instead of 1-125 seeds. Alternatively, the light-emitting diodes may be attached to an additional, outer rim. When the light-emitting diodes are housed in an outer rim, the outer rim can be a separate rim configured to be arranged around the inner rim. A separate outer rim can be attached to the eye before suturing the applicator comprising the radiation sources, so that the attachment of the separate rim will not cause radiation exposure to the surgical staff.

The device may be fabricated in accordance with well-established procedures that are known to a person skilled in the art. Inner and outer calottes for example can be prepared from titanium foil of appropriate thickness by deep-drawing.

Another aspect of the invention refers to an applicator for applying radiation to a target volume on or within the eye comprising a device according to the invention, and one or more radiation sources. The one or more radiation sources are housed within the device. Eye applicators usually are also denoted as plaque. The applicator is usable in episcleral plaque brachytherapy. As used herein, the term "radiation source" refers to a radioactive source material that has been adapted for use in a brachytherapy, particularly in ophthalmic brachytherapy. Suitable radioactive isotopes which can be effective in the treatment of ocular melanoma are selected from the group of iodine-125, ruthenium- 106, gold-198, and palladium- 103. Iodine-125 (I- 125) and ruthenium- 106 (Ru-106) are the most commonly used isotopes for in the treatment of ocular melanoma.

Suitable radiation sources are commercially available. Iodine-125 (1-125) radiation sources adapted for use in a brachytherapy, in particular in ophthalmic brachytherapy, are

commercially available in form of small, permanent, radioactive implants, so called seeds, for example at Eckert & Ziegler Bebig, Germany. The seeds can have the form of little capsules containing an appropriate quantity of the radioactive isotope, iodine-125. Such iodine-125 seeds suitable for use with the device can be rice-sized rods or cylinders of various

dimensions. Ruthenium- 106 (Ru-106) radiation sources adapted for use in a brachytherapy, in particular in ophthalmic brachytherapy, also are commercially available in form of radioactive implants comprising a thin silver foil embedded with Ru-106, so called Ru-106 applicators, for example at Eckert & Ziegler Bebig, Germany. Ru-106 applicators are offered in different variations of type and size, dependent on the indication for use. The plaques can be about 1 mm in thickness. The radiation source for use with the present device preferably is selected from the group consisting of 1-125 seeds and Ru-106 applicators.

In embodiments, the applicator can comprise one or more 1-125 seeds and a Ru-106 applicator. An applicator comprising two different radioactive isotopes is called a bi-nuclide applicator. The 1-125 seeds can be housed in the recesses of the rim, and a Ru-106 applicator can be housed in the body of the cavity between inner and outer calotte. Advantageously, the bi-nuclide applicator of the invention comprising one or more 1-125 seeds and a Ru-106 applicator can provide a combination of two radiation sources in a shell of very low thickness. The bi-nuclide applicator providing low thickness such facilitates the positioning on and suturing to the eye. Further, the bi-nuclide applicator causes lesser pressure to the eye ball and effects less discomfort and pain to the patient.

In alternative embodiments, the applicator can comprise several 1-125 seeds. In these embodiments, the 1-125 seeds can be housed the cavity between the inner calotte and the outer calotte, or in the calotte and in recesses in the rim. The cavity between the inner calotte and the outer calotte can be filled with plastic, silicone, or titanium, wherein the filling can comprise slots adapted for 1-125 seeds. In an alternative embodiment, the applicator can comprise a Ru-106 applicator.

The device and the applicator described herein may be used in eye or episcleral plaque brachytherapy. The device and the applicator may be used in the treatment of ocular diseases, which are treatable with radiation. Particularly, the applicator is usable in the treatment of macula degeneration, haemangioma, and ocular melanoma, particularly intraoccular tumours, such as choroidal melanoma, conjunctival melanoma, iris melanoma, and retinoblastoma.

Another aspect of the invention refers to a method of treating an eye, comprising directing radiation towards a target volume on or within the eye using an applicator comprising a device according to the invention and one or more radiation sources. The device as described herein comprises a housing, the housing comprising an inner calotte, and a rim coupled to the perimeter of the inner calotte, and an outer calotte, wherein the thickness of the rim defines a cavity between the inner calotte and the outer calotte, which is configured to accept one or more radiation sources, and wherein the housing comprises one or more fastening elements by means of which the outer calotte can be fastened releasable to the inner calotte and/or to the rim.

In an embodiment, the method may include assembling or otherwise preparing the applicator, affixing the applicator to an affected region of the eye, leaving the applicator affixed to the affected region for a sufficient period of time, and removing the applicator. After use, the applicator may be disassembled and the radiation sources may be disposed of.

Advantageously, the device may be reused.

Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The examples which follow serve to illustrate the invention in more detail but do not constitute a limitation thereof.

In the figures show:

Figure 1 Figure la is a cross sectional view of an embodiment of a device according to the invention. Figure lb is a top view on the device of Figure la.

Figure 2 Figure 2a is a top view on an embodiment of a device according to the invention comprising 1-125 seeds and a Ru-106. Figure 2b is a cross sectional view on the device of Figure 2a. Figure 2c is a cross sectional view on the Ru-106 applicator of Figure 2b. Figure 2d is a detailed cross sectional view on X in Figure 2b. Figure 2e is a detailed cross sectional view on Y in Figure 2b. Figure 2f shows in detail a iodine- 125 seed covered by a gold foil.

Figure 3 Figure 3a shows a top view (covering convex titan foil removed) on a device

comprising a Ru-106 applicator partially shielded by a gold foil. The unshielded area follows the shape of the target volume. Figure 3b is a detailed cross sectional view of Figure 3 a on position X as shown in Figure 2b.

Figure 4 Figure 4a shows a top view (covering convex titan foil removed) on an alternative embodiment of a device comprising 1-125 seeds in slots, and LEDs. Figure 4b is a cross section of Figure 4a, illustrating the geometry of the slots containing the 1-125 seeds.

Figure 5 Figure 5 a is a top view on an embodiment of a device comprising iodine-125 seeds and 3 LEDs fitted on the rim. Figure 5b is a cross sectional view on the device of Figure 5 a.

Figure la shows a cross sectional view of an embodiment of a housing 10 of a device according to the invention. The housing 10 comprises an inner calotte 12, which has a diameter of 21.39 mm. The inner calotte 12 has a radius S of 12.05 mm. Welded to the perimeter of the inner calotte 12 is a rim 14. The rim 14 has a thickness T of 1 mm and a height H of 2 mm. The housing 10 further comprises an outer calotte 16, which has a diameter of 23.73 mm. Between the inner calotte 12 and the outer calotte 16 is a cavity 18, which is defined by the thickness T of the rim 14. Figure lb shows a top view of the housing 10 of Figure la. The rim 14 comprises four bores 15.

Figure 2a shows a top view on an embodiment of an applicator comprising iodine-125 seeds 20. The iodine-125 seeds 20 are circularly arranged in recesses of the rim. The rim also contains four bores 15. Figure 2b is a cross sectional view on the applicator of Figure 2a comprising iodine-125 seeds 20 in recesses of the rim 14. Further, the applicator comprises a Ru-106 applicator 21 between the inner calotte 12 and the outer calotte 16. The inner calotte 12 and the outer calotte 16 have a thickness of 50 μιη and are made from titanium. The outer calotte 16 is screw-mountable to the rim 14 via the screws 25. Figure 2c shows a cross sectional view of the Ru-106 applicator 21 of Figure 2b, which has a thickness of 1 mm. Figure 2d shows a detailed cross sectional view on X in Figure 2b, showing inner calotte 12 and outer calotte 16 having both a thickness of 50 μιη and the Ru-106 applicator 21 in the cavity between inner calotte 12 and outer calotte 16. Figures 2e shows a detailed cross sectional view on Y in Figure 2b showing a iodine-125 seeds 20 in a recess 26 of the rim 14. Figure 2f shows in detail a iodine-125 seed 20, which is partially covered by a gold foil 24. Figure 3 a shows a top view (inner titan calotte 12 removed) on a device according to the invention comprising a Ru-106 applicator 21 partially shielded by a gold layer 24. To the outer calotte 16 suture eyelets 32 are attached. The rim 14 comprises screws 25 shown from the backside and LEDs 34. The area A shows the region shielded by the gold foil 24. The gold layer has a thickness of 200 μιη. The unshielded area B that is not covered by the gold layer follows the shape of the target volume, i.e. the tumour inclusive adjacent safety margins.

Figure 3b is a detailed cross sectional view of Figure 3a, on position X as shown in Figure 2b. The cavity 18 between the inner calotte 12 and the outer calotte 16 comprises a Ru-106 applicator 21. The inner calotte 12 and the outer calotte 16 have a thickness of 50 μιη. The Ru-106 applicator 21 has a thickness of 1 mm. Between the convex surface of the inner calotte 12 and the Ru-106 applicator 21 the cavity 18 also comprises a gold layer 24, having a thickness of 200 μιη.

Figure 4a shows a top view (inner titan calotte 12 removed) on an alternative embodiment of the device comprising 12 1-125 seeds 20 in slots 36, and LEDs 34. The number of seed slots 36 is arbitrary. Figure 4b is a schematic cross sectional view of Figure 4a. The cavity 18 between the inner calotte 12 and the outer calotte 16 is filled with silicone, and comprises I- 125 seeds 20 in slots 36. The inner calotte 12 and the outer calotte 16 have a thickness of 50 μιη. The 1-125 seeds 20 have a thickness of 0.8 mm. The slots have a thickness of 1 mm. The inner surface of the seed slots 36 is covered by a gold layer with a thickness of 25 μιη, with openings only in the directions of the intended application of the radiation. The outer calotte 16 is mounted to the inner calotte 12 by a central screw 25.

Figure 5 a shows a top view on an embodiment of an applicator comprising iodine-125 seeds 20. The iodine-125 seeds 20 are circularly arranged in recesses of the rim 14. The rim 14 also contains four bores 15. Three LEDs 34 and two suture eyelets 32 are fitted on the rim 14. Figure 5b is a cross sectional view on the applicator of Figure 5 a comprising iodine-125 seeds 20 in recesses of the rim 14. Further, the applicator comprises a Ru-106 applicator 21 between the inner calotte 12 and the outer calotte 16. The inner calotte 12 and the outer calotte 16 have a thickness of 50 μιη and are made from titanium. The outer calotte 16 is screw-mountable to the rim via the screws 25.

Example 1

Preparation of a bi-nuclide applicator

Inner and outer calottes were prepared from titanium foil (grade 1 titanium foil, Ankuro Int. GmbH, Germany) of 50μιη thickness by deep drawing. The inner calotte featured a radius of curvature of 12.05 mm. The outer calotte featured a radius of curvature of 13 mm. The inner calotte was cut to a height of 6.5 mm and the outer calotte was cut to a height of 7.6 mm with a diamond saw. The rim was turned out from a titanium rod (titanium 99.7%, Chempur GmbH, Germany) and equipped with thread holes and recesses for 1-125 seeds. The rim was welded to the inner, smaller calotte under argon atmosphere. The titanium capsule was equipped with shielding layers of gold foil with a thickness of 100 μιη and loaded with twelve I- 125 -seeds (IBt Bebig, type 125. SI 6) in four milled-out portions of the ring and an Ru-106- applicator (IBt Bebig , type CCB). Monte Carlo Simulations using the code EGSnrc showed that the titanium calotte decreased the radiation intensity of 1-125 and Ru-106 by 20%. The gold shielding decreased the radiation intensity to about 1% of the original value.

Example 2

Dosimetric measurement of the applicator

The bi-nuclide applicator as described in example 1 was used for the dosimetric

measurements.

The measurements were performed using a plastic scintillator detector system, as described in M. Eichmann, Med. Phys. 36 (10) October 2009, p 4634-4634. The measured dose distributions were obtained by scaling of the measurement signal. The contribution originating from the Ru-106-plaque and the I-125-seeds respectively were measured separately because the detector system possesses different calibration factors for the different kinds of radiation.

The titanium device as described in example 1 and fig. 1 was first equipped with shielding layers of gold foil with a thickness of 100 μιη and then loaded with three I-125-seeds (IBt Bebig, type 125. SI 6) in one milled-out portion of the rim and an inactive Ru-106-dummy- applicator (Type CCB, IBt Bebig). A dose profile perpendicular to the longitudinal axis of the central seed was then measured, covering the inner region of the applicator and a region above the applicator to a distance of 20 mm with a step width of 1 mm using a xyz-measuring table. In the next step a dose profile perpendicular to the first one and intersecting at the centre of the applicator was measured in the same way. The relative dose distribution of an applicator loaded with 12 seeds was derived from these measurements by superposition. The corresponding dose distribution of the Ru-106-applicator (IBt Bebig, Type CCB) was measured separately. To obtain the dose distribution of the fully loaded applicator, the properly weighted dose distributions had to be added. Provided that different sources of the same type are reasonably similar, one can use the measured normalized dose distributions of the applicator to simulate the bi-nuclide applicator loaded with sources that have different activities. Monte Carlo simulations of the bi-nuclide applicator were performed using the Monte Carlo code EGSnrc.

These simulations showed that the weights one would choose to create a well balanced dose distribution avoiding excessive hot spots in the sclera correspond to commercially available source strengths. Additional measurements with the polar measuring table described in M. Eichmann, Med. Phys. 36 (10) October 2009, p 4634-4634 lead to an estimated value of approx. 730% of the value attained in a depth of 11 mm on the central axis of the applicator. This value was averaged over a volume of 0.25 mm ³ within the sclera. A transfer of this result to the case were a 10mm thick tumour is irradiated with 85 Gy to the tumour apex, translates to a maximum value of approx 620 Gy in the sclera. These values meet the criteria applied to dose distributions used for the treatment of ocular melanoma. These experiments show that a preliminary dosimetric measurements of the bi-nuclide applicator shows satisfying results.