Alpha-emitting radionuclides for use in the treatment of peritoneal cancer

Abstract

The present invention relates to pharmaceutical compositions comprising a therapeutically relevant amount of alpha emitting radionuclides, for use in the treatment of cancer, and specifically where the individual has received cytoreductive surgery of one or more peritoneal tumor(s) prior to the administration of the pharmaceutical composition.

Description

Title: Alpha-Emitting Radionuclides for Use in the Treatment of Peritoneal Cancer Abstract: The present invention relates to pharmaceutical compositions comprising a therapeutically relevant amount of alpha-emitting radionuclides, for use in the treatment of cancer, and specifically where the individual has received cytoreductive surgery of one or more peritoneal tumors prior to administration of said pharmaceutical composition.

Claims

CLAIMS1 . A pharmaceutical composition comprising a therapeutically relevant amount of alpha emitting radionuclides, wherein the alpha emitting radionuclides or progeny is dosaged, and can be administered, with a radiation dose range of 6 Gy (30 Sv) to 2000 Gy (10 000 Sv), more specifically 10-200 Gy (50-1000 Sv).

2. The pharmaceutical composition according to any one or more of the previous claims, wherein the radionuclide is selected from the group consisting of alpha-radionuclides suitable for therapy consisting of224Ra,225Ac,211At,213Bi,212Bi,223Ra,149Tb,230U,255Fm, and227Th.

3. The pharmaceutical composition according to any one or more of the previous claims, wherein the radionuclide is selected from the group consisting of alpha-emitting224Ra with the progeny radionuclides220Rn,216Po,212Pb,212Bi,212Po and208TI.

4. The pharmaceutical composition according to any one or more of the previous claims, wherein the radionuclide is a beta emitter with alpha-progenies suitable for therapy, which is212Pb with progeny radionuclides212Bi,212Po and208TI.

5. The pharmaceutical composition according to any one or more of the previous claims, wherein the alpha emitting radionuclide is comprised in a particle, which can be biodegradable.

6. The pharmaceutical composition according to claims 6-7, wherein the particles furthermore comprise a phosphorus containing additive.

7. The pharmaceutical composition according to claims 6-8, wherein the degradable compound is selected from the group consisting of CaCOs, MgCOs, SrCOs, BaCOs, calcium phosphates including hydroxyapatite Ca5(PO4)3(OH) and fluoroapatite, and composites with any of these as a major constituent.

8. The pharmaceutical composition according to claims 8-10, wherein the phosphorus containing additive is a phosphate selected from the group consisting of orthophosphate, linear oligophosphates and polyphosphates, and cyclic polyphosphates.

9. The pharmaceutical composition according to claim 8, wherein the phosphonate is a polyphosphonate.

10. The pharmaceutical composition according to claim 9, wherein the polyphosphonate is selected from the group consisting of EDTMP-ethylenediamine tetra(methylene phosphonic acid), DOTMP- 1 ,4,7, 10-Tetraazacyclododecane-1 ,4,7,10-tetrayl- tetrakis(methylphosphonic acid) and DTPMP-diethylenetriaminepenta(methylene- phosphonic acid).

11. The pharmaceutical composition according to claim 10, wherein the polyphosphonate is EDTMP-ethylenediamine tetra(methylene phosphonic acid).

12. The pharmaceutical composition according to any one or more of the previous claims, wherein the size of the particle is from 1 nm to 500 pm.

13. The pharmaceutical composition according to any one or more of the previous items, wherein the average particle size is 0.1-30 pm, such as 1-10 pm, and which is radiolabelled with 1-2000 atoms of alpha emitter per particle, such as 50-1000 atoms per micro-particle.

14. The pharmaceutical composition according to any one or more of the previous claims, prepared with an amount of radionuclide that is 1kBq to 10GBq per dosing or with an amount of radionuclide that is 50 MBq to 100 GBq suitable for multidose industrial scale production.

15. The pharmaceutical composition according to any one or more of the previous claims, wherein 0.1-10 gram of particles is used per dosing, such as 0.5-5 gram of particles per dosing.

16. The pharmaceutical composition according to any one or more of the previous claims, wherein there is 2 MBq to 50 MBq of224Ra per gram of microparticles.

17. The pharmaceutical composition according to any one or more of the previous claims for use in the treatment of cancer.

18. The pharmaceutical composition for use according to any one or more of the previous claims, wherein the cancer is selected from the group consisting of intraperitoneal cancers, intracranial cancers, pleural cancers, bladder cancers, cardiac cancers, and cancers in the subarachnoid cavity.

19. The pharmaceutical composition according to any one or more of the previous claims, wherein the individual has received cytoreductive surgery of one or more peritoneal tumor(s) prior to the administration of the pharmaceutical composition.

20. The pharmaceutical composition for use according to any one or more of the previous claims, wherein the pharmaceutical composition is administered to an individual in needed thereof.21 . A particle of numerical diameter size 0.1-30 urn, such as 1-10 urn, radiolabelled with 1- 2000 atoms of alpha emitter per particle, such as 50-1000 atoms per micro-particle.

22. A particle according to claim 21 radiolabelled with an alpha emitter, such as224Ra, and administered as a suspension using a radioactivity dosage of 1-50 MBq, such as 4-20 MBq, such as 5-10 MBq per patient.

23. A suspension of alpha emitter-labeled particles, such as crystalline particles, according to any of the previous claims, containing 50-3000 mg such as 500-1500 mg for intraperitoneal infusion and with an activity of 1 MBq - 500 MBq, such as 4-12 MBq and dispersed in 1- 2000 ml such as 10-500 ml such as 100-300 ml.

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