Layer structure for epidermal radionuclide therapy

Abstract

Disclosed is a layer structure for epidermal radionuclide therapy (brachytherapy) of a patient comprising, from a patient's view, a proximal adherent layer for applying the layer structure on the skin surface to be treated of a patient; a flexible, transparent carrier layer that from a patient's view is located in a distal direction on the adherent layer; and at least one radionuclide-containing emission layer located on the carrier layer, the adherent layer and the carrier layer with regard to their components and thickness being formed such that they are essentially transparent for and radiation. The layer structure is suited particularly for radiotherapeutic treatment of the basal-cell carcinoma (BCC) and the squamous cell carcinoma (SCC). With the aid of the layer structure, geometrically complex skin lesions caused by a tumor, as occurring e.g. on the outer edge of the auricle, may be treated easily.

Claims

1. A layer structure for epidermal radionuclide therapy of a patient, comprising: a proximal adherent layer adapted for application of the layer structure on a patient's skin surface, the adherent layer comprised of a synthetic film sprayable onto the skin surface, the adherent layer excluding a skin gel; a flexible, transparent carrier layer located in a distal direction on top of the adherent layer, wherein the adherent layer is located on a proximal side of the carrier layer, and the carrier layer having an outer periphery with at least one zone without adhesive, wherein the carrier layer consists of a single layer, free from enclosure and is applied directly on top of the adherent layer without an intermittent layer; and an emission layer located on the carrier layer wherein the emission layer contains at least one radionuclide selected from a group consisting of .sup.32P, .sup.90Y, .sup.166Ho, .sup.177Lu, and .sup.188Re, wherein the adherent layer and the carrier layer with regard to their components and thicknesses are formed such that they are essentially transparent for , and radiation, and further wherein the adherent layer is sprayable onto the skin surface on the proximal side of the carrier layer prior to an assembling of the layer structure, wherein the synthetic film is formed of a liquid bandage including polyurethanes and/or polyacrylates; wherein the carrier layer is selected from the group consisting of polyurethane foil and polyamide foil, and wherein the emission layer is a water-based polyacrylate matrix including homogenously spread .sup.188rhenium sulfide.

2. The layer structure according to claim 1, wherein the adherent layer has a thickness of 1 to 80 m.

3. The layer structure according to claim 1, wherein the carrier layer further includes an adherent layer, the carrier layer being formed as a self-adhering layer.

4. The layer structure according to claim 1, wherein the carrier layer is formed as a foil having a thickness of 15 to 80 m.

5. The layer structure according to claim 1, wherein the emission layer distally has a covering layer.

6. The layer structure according to claim 5, wherein the covering layer with regard to its consistency and thickness is formed such that the covering layer is essentially impermeable to the , and radiation emitted by the at least one radionuclide of the emission layer.

7. The layer structure according to claim 6, wherein the covering layer is polyester or polypropylene or an aluminum foil laminated with polyester, polyethylene or polypropylene which has a thickness of 100 to 200 m.

8. The layer structure according to claim 1, wherein the emission layer further comprises .sup.188Re.sub.2S.sub.7 as a dispersion.

9. A method of applying a layer structure for epidermal radionuclide therapy of a patient, comprising: applying a proximal adherent layer on a patient's skin surface to be treated, the adherent layer comprised of a synthetic film sprayable onto the skin surface, the adherent layer excluding a skin gel; applying a flexible, transparent carrier layer in a distal direction on the adherent layer, wherein the adherent layer is located on a proximal side of the carrier layer, and the carrier layer having an outer periphery with at least one zone without adhesive wherein the carrier layer consists of a single layer, free from enclosure and is applied directly on top of the adherent layer without an intermittent layer; and applying at least one radionuclide-containing emission layer located on the carrier layer wherein the radionuclide is selected from a group consisting of .sup.32P, .sup.90Y, .sup.166Ho, .sup.177Lu, and .sup.188Re, wherein the adherent layer and the carrier layer with regard to their components and thickness are formed such that they are essentially transparent for , and radiation, wherein the adherent layer is formed on the skin surface prior to applying the carrier layer.

10. The method according to claim 9, wherein the sprayable synthetic film is formed of a liquid bandage consisting of polyurethanes or polyacrylates.

Description

EXAMPLE

(1) Preparation of the Patient

(2) Prior to treatment with the selected radionuclide, .sup.188Re in the example, the lesion is to be examined by a dermatologist and the area to be treated is to be determined. This area is then marked with a pen pleasant to the skin. The surface of the marked area that is to be treated with the radioactive nuclide, has to be determined. This is done by computer-aided evaluation of a photograph or a scan of the marked area to be treated.

(3) For treatment, the patient is brought into a position that for the most part makes horizontal application of the liquid matrix possible, so that it does not run. As a rule, the patient lies on a couch and moreover care has to be taken that the posture is comfortable to the patient since he/she has to remain in the position for 1-3 hours.

(4) The dose of radiation of the selected radionuclide, i.e. .sup.188Re in this case, is computed using methods known per se.

(5) Prior to the treatment, the skin lesion to be treated is to be cleaned and drained. Any possibly existing scab is to be removed carefully. Moreover, the lesion may not bleed or deliver secretions. In case bleedings occur, suitable hemostatic measures that are known per se are used.

(6) A liquid bandage on the basis of polyurethane is directly applied to the skin lesion and the surrounding skin as adherent layer. Subsequently, one has to wait for a few seconds until no more solvents can be detected.

(7) Measurements on such sprayed adherent layers have shown that they have a thickness in the range of 3-60 m and, contrary to general expectations, exhibit comparatively little deviations in layer thickness.

(8) A sterile, very thin, approximately 35 m thick transparent medical polyurethane foil is applied to the skin portion with the adherent layer and is carefully pressed on. The polyurethane foil serves as a carrier layer. The carrier layer foil adheres to the adherent layer and is thus fixed. The substance and thickness in a two-digit m range make it possible for the carrier foil to adapt to even complex geometrical lesions, such as on the edge of the Helix auriculae or in the nasolabial fold, in a crease-free manner while ensuring at the same time that the distance of the surface of the lesion to the (patient-side) proximal side of the emission layer is essentially equal. This ensures an equal dose of radiation for all areas of the lesion to be treated.

(9) The carrier layer foil is adhered to the skin such that loose areas exist on the edge that are not tied to the adherent layer, so that the carrier layer foil later may be grabbed with the aid of specifically configured forceps (such as the tool described in German utility model DE 20 2010 005 805 U1) and the overall layer structure may be removed from the adherent layer and hence the lesion. The carrier layer should be considerably larger than the lesion, so that the skin around is completely covered by the foil.

(10) Preparation of the Treatment

(11) The radioactive agent, .sup.188Re in the present case, is delivered from a corresponding plant of nuclear physics in a so-called carpule designed as disposable article and loaded with a volume of 0.3 ml each, with activities of up to 2.2 GBq per carpule at the time of supply to the hospital. Due to the fairly low half-life of .sup.188Re of about 16.7 hours the manufacturer correspondingly has to calibrate higher so as to ensure the amounts of radioactivity on the application site.

(12) Delivery is effected in a shielded transport container and the carpules are taken only shortly before the application. The carpule itself contains .sup.188Re in form of a .sup.188Re.sub.2S.sub.7 as a dispersion in an acrylate-water-TiO.sub.2-based matrix suspension as colloid having an average particle diameter of approximately 500 nm in the present example.

(13) Prior to withdrawal of the radioactive mixture from the carpule the carpule is again mixed. For this purpose, the carpule contains a mixing element made of metal which being driven from outside is moved up and down within the carpule, so that all components of the matrix, particularly the TiO.sub.2 and the .sup.188Re particles, are mixed with each other.

(14) Subsequently, an applicator in accordance with DE102009054388 known per se is loaded with each carpule. The next step includes the determination of the actual amount of radioactivity contained in the loaded carpule at the time of application. The activity at the time of application is determined via a simple subtraction method (measurement of the activity of the carpule prior to the treatment, same measurement after the treatment, the resulting activity of the measurement of the difference thus was used for treating the patient and his/her lesion).

(15) In particular, the applicator with inserted carpule is measured in a specific activimeter. In the example, the activimeter is a specific well-type ionization chamber of MED Medizintechnik Dresden GmbH. After the measurement, applicator and carpule are ready for the treatment.

(16) TreatmentApplication of the Emission Layer Matrix

(17) The carpule is activated for treatment in that the head of the carpule is pressed with the applicator. The carpule is thus pushed together and a needle pierces through the diaphragm which previously retained the radioactive contents.

(18) After removing the sheath from the carpule, treatment may start. The attending physician spreads the carrier layer foil over the skin in the previously marked area of the skin lesion with the polyacrylate matrix, so that the whole area is covered uniformly to thereby form the emission layer that contains the .sup.188Re.sub.2S.sub.7. The applicator is formed in two parts, one part being formed as a thick pen so as to be easy to handle. Moreover, a hand shield is provided which protects the physician against radioactive radiation. Dosage of the matrix and the radioactive amount is done via the second part of the applicator.

(19) The viscous .sup.188rhenium-containing polyacrylate matrix of the emission layer hardens within 10 to 20 minutes without shrinking essentially. Subsequently to the application of the emission layer, a polyester-laminated aluminum foil having a thickness of approximately 100 m is applied onto the still slightly wet emission layer on the distal side thereof, which thus adheres to the polyacrylate matrix.

(20) When the surface to be treated was covered and the application is terminated, the sheath is put on the carpule again. Afterwards, the activity of the carpule in the applicator is again determined with the aid of the above-indicated specific activimeter. The applied radioactive quantity of .sup.188Re may be determined from the difference of the activity measurements. With the activity applied and the covered area the length of the treatment may be calculated. As a rule, the length of the treatment is between 1 and 3 hours.

(21) Tables 1 to 4 serve as guidance for the length of the treatment as a function of the surface of the skin area to be treated.

(22) TABLE-US-00001 TABLE 1 Application time on the basis of an energy dose of 50 Gy for a required penetration depth of 300 m Treatment Specific Irradiation area radioactivity time [cm.sup.2] [MBq/cm.sup.2] [min] 1 74 43 3 74 40 10 74 38

(23) TABLE-US-00002 TABLE 2 Application time on the basis of an energy dose of 50 Gy for a required penetration depth of 400 m Treatment Specific Irradiation area radioactivity time [cm.sup.2] [MBq/cm.sup.2] [min] 1 74 49 3 74 45 10 74 43

(24) TABLE-US-00003 TABLE 3 Application time on the basis of an energy dose of 50 Gy for a required penetration depth of 500 m Treatment Specific Irradiation area radioactivity time [cm.sup.2] [MBq/cm.sup.2] [min] 1 74 55 3 74 50 10 74 48

(25) TABLE-US-00004 TABLE 4 Application time on the basis of an energy dose of 50 Gy for a required penetration depth of 600 m Treatment Specific Irradiation area radioactivity time [cm.sup.2] [MBq/cm.sup.2] [min] 1 74 61 3 74 55 10 74 53

(26) In treating large lesions it has turned out that for the purpose of a minimum radiation exposure of the patient and efficient treatment at the same time it is sufficient to reduce the treatment times as compared to smaller areas to be treated. As is to be seen from the above tables 1 to 4, a reduction of the irradiation time by approximately 12% in a lesion with a surface of about 10 cm.sup.2 as compared to one with only 1 cm.sup.2 has turned out to be favorable.

(27) In the example of a skin lesion with a surface of approximately 3 cm.sup.2 diagnosed histologically as basal-cell carcinoma of the nasolabial area, the length of the treatment was approximately 55 minutes (energy dose of 50 Gy for a penetration depth of 600 m, specific radioactivity [MBq/cm.sup.2].sup.188Re, the applied volume was approximately 30 l).

(28) After the application, the carpule is disposed of in a suitable shielded waste container. Due to the low half-life of 16.7 hours the radioactivity of the .sup.188Re abates within approximately 10 days.

(29) Removal of the Emission Layer

(30) After a length of treatment of 55 minutes the carrier layer foil on the skin lesion with the applied and meanwhile dried-up emission layer which was provided with a covering foil, is peeled off the skin of the patient using long forceps and subsequently is disposed of in a shielded waste container.

(31) The patient's skin is cleaned after treatment and examined for radiating residues.

(32) On account of the layer structure in accordance with the invention consisting of adherent layercarrier layeremission layer and in the example an additional covering layer, radioactive contamination was detected in none of approximately 500 cases of treatment.

(33) As a possible side effect a slight rush of the treated area could be observed in some patients. After examinations after 2, 4 and 12 weeks and subsequently within a time lag of six months, 85% of the cases were cured without requiring further treatment.

(34) Merely in a few cases it was necessary to perform a second andvery rarelya third follow-up treatment, which then all led to success.

(35) Follow-up studies of up to 44 months after the first treatment showed a cure of BCC and SCC of 85 to 90%.