RADIOISOTOPE SOURCE

1 . A layered radioisotope source for generating a medically useful dose of daughter radioisotope through a chain of spontaneous decay from a parent radioisotope via a gaseous intermediate radioisotope, comprising:

an inert ceramic substrate layer;

a metal oxide surface layer bound on the inert ceramic substrate layer; and

parent radioisotope immobilised on or within the metal oxide surface layer to allow for effective emanation of the gaseous intermediate radioisotope away from the layered radioisotope source.

2 . The layered radioisotope source of claim 1 , wherein the metal oxide surface layer is a sol-gel reaction product.

3 . The layered radioisotope source of claim 1 or claim 2 , wherein the metal oxide surface layer is a calcined metal oxide surface layer.

4 . The layered radioisotope source of any one of claims 1 to 3 , wherein the metal oxide surface layer comprises less than about 1000, 5000, 1000, 500, 100, 80, 60, 40, 20, 10, 5 or 1 discrete deposits of the radioisotope having a particle size of about 20 nm or more bound on or within the surface of the metal oxide surface layer per cm 2 of metal oxide surface layer.

5 . The layered radioisotope source of any one of claims 1 to 3 , wherein the metal oxide surface layer is substantially free of discrete deposits of the radioisotope having a particle size of about 20 nm or more bound on or within the surface of the metal oxide surface layer.

6 . The layered radioisotope source of any one of claims 1 to 5 , wherein the immobilised parent radioisotope are uniformly distributed within the metal oxide surface layer.

7 . The layered radioisotope source of any one of claims 1 to 6 , wherein the metal oxide surface layer has a thickness of between about 0.1 nm to about 1000 nm.

8 . The layered radioisotope source of any one of claims 1 to 7 , wherein the metal oxide surface layer has molar ratio of metal forming the oxide of the surface layer to immobilised parent radioisotope (M: R) of between greater than 1 to about 10.

9 . The layered radioisotope source of any one of claims 1 to 8 , wherein the metal oxide surface layer is an oxide of a valve metal, a refractory metal or another transition or main-block metal.

10 . The layered radioisotope source of any one of claims 1 to 9 , wherein the metal oxide surface layer is an oxide of tantalum, niobium, tungsten, molybdenum, vanadium, zirconium, or titanium, or a mixed oxide thereof.

11 . The layered radioisotope source of any one of claims 1 to 10 , wherein the metal oxide surface layer is tantalum pentoxide (Ta 2 O 5 )

12 . The layered radioisotope source of any one of claims 1 to 11 , wherein the metal oxide surface layer and at least some of the immobilised parent radioisotope together form one or more mixed oxide phases within the metal oxide surface layer.

13 . The layered radioisotope source of any one of claims 1 to 12 , wherein the metal oxide surface layer and immobilised parent radioisotope form a mixed oxide surface layer on the inert ceramic substrate.

14 . The layered radioisotope source of claim 12 or claim 13 , wherein the mixed oxide phase or mixed oxide surface layer has the formula R x M y O z , wherein R is a parent radioisotope in cationic form, M is one or more metals in cationic form, 0.1≤x≤5, 1.0≤y≤20, 1.0≤z≤50, preferably wherein x<y.

15 . The layered radioisotope source of any one of claims 1 to 14 , wherein the inert ceramic substrate layer has a thickness (in μm) of between about 1 to about 1000.

16 . The layered radioisotope source of any one of claims 1 to 15 , wherein the inert ceramic substrate layer is selected from an inert oxide, an inert nitride, an inert carbide, an inert sulfide, an inert phosphate or combination thereof.

17 . The layered radioisotope source of any one of claims 1 to 16 , wherein the inert ceramic substrate layer is selected from a metal oxide, metal nitride, metal carbide, metal sulfide, metal phosphate or combination thereof.

18 . The layered radioisotope source of any one of claims 1 to 17 , wherein the inert ceramic substrate layer is an oxide of silicon, tantalum, niobium, tungsten, molybdenum, vanadium, zirconium, titanium or aluminium, or mixed oxides thereof.

19 . The layered radioisotope source of any one of claims 1 to 18 , wherein the inert ceramic substrate layer is quartz, tantalum pentoxide (Ta 2 O 5 ) or zirconium dioxide (ZrO 2 ).

20 . The layered radioisotope source of any one of claims 1 to 19 , wherein the inert ceramic substrate layer is provided on a metal substrate.

21 . The layered radioisotope source of claim 20 , wherein the metal substrate is selected from the group consisting of tantalum, niobium, tungsten, hafnium, molybdenum, vanadium, zirconium, titanium or aluminium, or alloys thereof.

22 . The layered radioisotope source of claim 20 or claim 21 , wherein the inert ceramic substrate layer is produced by oxidatively pre-treating the surface of the metal substrate.

23 . The layered radioisotope source of any one of claims 20 to 22 , wherein the metal substrate has a density (in g/cm 3 ) of between about 2.0 to about 20.

24 . The layered radioisotope source of any one of claims 20 to 23 , wherein the metal substrate has a thickness (in mm) of between about 1 to 100.

25 . The layered radioisotope source of any one of claims 1 to 24 , wherein the immobilised parent radioisotope within the metal oxide surface layer is such that, in use, it enables the capture of a population of daughter radioisotope having a contamination level of parent radioisotope of less than about 5% expressed in activity terms relative to the activity of the daughter radioisotope.

26 . The layered radioisotope source of any one of claims 1 to 25 , wherein the layered radioisotope source is provided as a disk or slab.

27 . The layered radioisotope source of any one of claims 1 to 26 , wherein the layered radioisotope source has a thickness (in mm) of between about 1 to 100.

28 . The layered radioisotope source of any one of claims 1 to 28 , wherein the parent radioisotope is an alpha-emitting radioisotope.

29 . The layered radioisotope source of any one of claims 1 to 28 , wherein the parent radioisotope is a thorium radioisotope selected from thorium-227 ( 227 Th) or thorium-228 ( 228 Th).

30 . The layered radioisotope source of any one of claims 1 to 29 , wherein the daughter radioisotope is a lead radioisotope selected from at least one of lead-211 ( 211 Pb) or lead-212 ( 212 Pb).

31 . The layered radioisotope source of any one of claims 1 to 30 , wherein the immobilised parent radioisotope is present in an amount effective to provide an activity (in MBq per cm 2 of inert ceramic substrate surface) of between about 1 to about 1500.

32 . A sol-gel process for preparing a layered radioisotope source for generating a medically useful dose of daughter radioisotope through a chain of spontaneous decay from a parent radioisotope via a gaseous intermediate radioisotope, comprising:

a) providing on the surface of an inert ceramic substrate layer a gel formed from a solution (e.g. sol) comprising a metal alkoxide and a parent radioisotope:

b) heating the gel under conditions effective to form a metal oxide surface layer bound on the inert ceramic substrate layer,

wherein the parent radioisotope is immobilised on or within the metal oxide surface layer to allow for effective emanation of the gaseous intermediate radioisotope away from the layered radioisotope source.

33 . The sol-gel process of claim 32 , wherein the process is for preparing a layered radioisotope source of any one of claims 1 to 31

34 . The sol-gel process of claim 32 or claim 33 , wherein after step a) but prior to step b), the gel is dried.

35 . The sol-gel process of claim 34 , wherein the gel is dried at a temperature (in ° C.) of between about 10 to about 180, and preferably for a period of time (in hours) of between about 0.1 to about 100.

36 . The sol-gel process of any one of claims 32 to 35 , wherein the solution at step a) comprises an alcoholic solution of the metal alkoxide and parent radioisotope species.

37 . The sol-gel process of claim 36 , wherein the alcoholic solution of metal alkoxide and parent radioisotope species comprises an alcohol solvent in amount (in % v/v based on the total volume of the solution) of between about 50 to 99.

38 . The sol-gel process of any one of claims 32 to 37 , wherein the metal alkoxide is in stoichiometric excess relative to the parent radioisotope species.

39 . The sol-gel process of any one of claims 32 to 38 , wherein molar ratio of metal alkoxide to parent radioisotope species is between greater than 1 to about 10.

40 . The sol-gel process of any one of claims 32 to 39 , wherein the parent radioisotope species is provided in the solution at a concentration of between about 0.000001 M to about 0.01 M.

41 . The sol-gel process of any one of claims 32 to 40 , wherein the metal alkoxide is provided in the solution at a concentration of between about 0.000050 M to about 0.01 M.

42 . The sol-gel process of any one of claims 32 to 41 , wherein the solution further comprises water and/or an acid.

43 . The sol-gel process of claim 42 , wherein the acid is provided in the solution at a concentration of between about 0.1 M to about 1 M

44 . The sol-gel process of any one of claims 32 to 43 , wherein the gel is heated at step b) at a temperature (in ° C.) of between about 200 to about 500, and preferably for a period of time (in minutes) of between about 30 to about 360.

45 . The sol-gel process of any one of claims 32 to 44 , wherein the metal alkoxide is an alkoxide of a valve metal, a refractory metal or another transition or main-block metal.

46 . The sol-gel process of any one of claims 32 to 45 , wherein the metal alkoxide is an alkoxide of tantalum, niobium, tungsten, molybdenum, vanadium, zirconium, or titanium, or a mixed oxide thereof.

47 . The sol-gel process of any one of claims 32 to 46 , wherein the metal alkoxide is tantalum alkoxide, preferably tantalum ethoxide.

48 . The sol-gel process of any one of claims 32 to 47 , wherein the parent radioisotope species is provided as a salt or hydrate thereof selected from one or more of hydroxides, halides, phosphates, nitrates, acetates, sulfates, perchlorates, ammonium compounds and anionic oxo-metallate compounds.

49 . The sol-gel process of any one of claims 32 to 48 , wherein the parent radioisotope species is a thorium species.

50 . The sol-gel process of claim 49 , wherein the thorium species is a nitrate salt or hydrate thereof.

51 . A radioisotope generator defining a chamber for producing and capturing a population of daughter radioisotope, wherein the chamber is configured to house a layered radioisotope source of any one of claims 1 to 31 in the chamber.

52 . The radioisotope generator of claim 51 , wherein the chamber comprises a collection surface and is configured to house the layered radioisotope source in the chamber with the metal oxide surface layer facing the collection surface for collecting at least some of the emanated gaseous intermediate radioisotope for a period of time effective for it to decay into daughter radioisotope.

53 . The radioisotope generator of claim 52 , wherein the metal oxide surface layer is in line-of-sight configuration with the collection surface.

54 . The radioisotope generator of claim 52 or claim 53 , wherein the metal oxide surface layer substantially faces downwards to enable gravity assisted collection of at least some of the emanated gaseous intermediate radioisotope on the collection surface.

55 . The radioisotope generator of any one of claims 52 to 54 , further comprising a carrier gas inlet port configured to introduce a carrier gas into the chamber to facilitate transfer of emanated gaseous intermediate radioisotope away from the layered radioisotope source onto the collection surface.

56 . The radioisotope generator of any one of claims 52 to 55 , further comprising a vacuum pump configured to apply a vacuum and evacuate the chamber to facilitate transfer of emanated gaseous intermediate radioisotope away from the layered radioisotope source onto the collection surface.

57 . The radioisotope generator of any one of claims 52 to 56 , further comprising a fluid delivery system configured to introduce a collection fluid into the chamber to collect daughter radioisotope from the collection surface.

58 . The radioisotope generator of claim 57 , further comprising a collection fluid outlet port configured to transfer the collection fluid comprising daughter radioisotope from the chamber.

59 . A system for producing and capturing a population of daughter radioisotope, comprising:

a) a radioisotope generator defining a chamber for producing and capturing a population of daughter radioisotope; and

b) a layered radioisotope source of any one of claims 1 to 31 housed in the chamber.

60 . The system of claim 59 , comprising a radioisotope generator of any one of 51 to 57 .

61 . A process for producing and capturing a population of daughter radioisotope comprising:

a) allowing for the emanation of a gaseous intermediate radioisotope generated through a chain of spontaneous decay from a parent radioisotope immobilised on or within a layered radioisotope source of any one of claims 1 to 31 , and

b) collecting at least some of the gaseous intermediate radioisotope for a period of time effective for it to decay into a daughter radioisotope.

62 . The process of claim 61 , comprising a radioisotope generator of any one of claims 51 to 57 , or a system of claim 59 or claim 60 .

63 . The process of claim 61 or claim 62 , wherein the process further comprises a step of recovering at least some of the daughter radioisotope.

64 . The process of claim 63 , wherein the recovered daughter radioisotope is conjugated to a targeting molecule for use in radioligand therapy.

65 . The process of claim 64 , wherein the targeting molecule is a cancer cell targeting molecule.

66 . The process of any one of claims 61 to 65 , wherein the parent radioisotope is an alpha-emitting radioisotope.

67 . The process of any one of claims 61 to 66 , wherein the parent radioisotope is a thorium radioisotope selected from at least one of thorium-227 ( 227 Th) and thorium-228 ( 228 Th).

68 . The process of any one of claims 61 to 67 , wherein the gaseous intermediate radioisotope is a radon radioisotope selected from at least one of radon-219 ( 219 Rn) and radon-220 ( 220 Rn).

69 . The process of any one of claims 61 to 68 , wherein the daughter radioisotope is a lead radioisotope selected from at least one of lead-211 ( 211 Pb) or lead-212 ( 212 Pb).