WO2009053876A2

WO2009053876A2 - Nir emitters excitable in the visible spectral range and their application in biochemical and medical imaging

Info

Publication number: WO2009053876A2
Application number: PCT/IB2008/054281
Authority: WO
Inventors: Thomas J. JÜSTEL; Helga Hummel; Petra Huppertz; Jacqueline Merikhi; Cornelis R. Ronda; Detlef U. Wiechert
Original assignee: Philips Intellectual Property & Standards Gmbh; Koninklijke Philips Electronics N. V.
Priority date: 2007-10-23
Filing date: 2008-10-17
Publication date: 2009-04-30
Also published as: WO2009053876A3

Abstract

This invention concerns the application of inorganic luminescent nanoscale particles, which exhibit optical transitions in the visible spectral range, which can be exploited for excitation purposes and which show an emission band or lines in the NIR range, preferably between 650 and 1100 nm. These nanoscale particles are eventually coated by SiO 2 or other inert oxides, e.g. Al2O3, in order to decrease toxicity and to enhance particle lifetime in living systems.

Description

NIR EMITTERS EXCITABLE IN THE VISIBLE SPECTRAL RANGE AND THEIR APPLICATION IN BIOCHEMICAL AND MEDICAL IMAGING

FIELD OF THE INVENTION

Subject of the present invention are NIR Emitters Excitable in the Visible Spectral Range and their Application in Biochemical and Medical Imaging.

BACKGROUND OF THE INVENTION

Optical imaging, in general, uses radiation between the near UV (ultraviolet) and the NIR (near-infrared) spectral range to investigate cells, tissue or organs. Nowadays, it is well known that penetration depth of electromagnetic radiation into biological matter strongly depends on the wavelength due to the fact that the absorption coefficient of water and relevant biochemical molecules is a sensitive function of the wavelength. In the spectral range less than 650 nm, light absorption in tissue is relatively high resulting in a small penetration depth of hundreds of micrometers up to a few millimeters, which is only suitable for the superficial investigation of tissue or organ surfaces. To image a larger tissue volume, light within the NIR spectral range (650 to 1100 nm) is required, since penetration depth reaches up to a few centimeters. Thus, the identification of changes of morphology and/or function of tissue even in thick layers is feasible.

Contrast agents with intense emission in the NIR region are particularly useful because biological tissues are optically transparent in this region. The absorption and scattering of light in biological tissue can be illustrated by shining a torch light at one's hand. It is possible to see a reddish glow, but not the outline of the bones that are in the path of the beam. The bones are not visible because the light is multiply scattered in the tissue. The reddish glow is readily understood from the absorption profile of the most common constituents of biological tissue. There is an absorption minimum in the near infrared around 830 nm that will preferentially transmit the red components of the beam rather than the shorter visible wavelengths. The relatively high-transmission spectral region between 650 to 1100 nm is often described as the "optical window" of biological tissue (Fig. 1).

In vivo optical imaging is a very sensitive tool for the judgment of cell and tissue anatomy and molecular functions. At present, mainly organic dyes, which exhibit so-called (auto)fluorescence are applied to enhance contrast in optical imaging experiments and various other biomedical applications [Krause, W.: Contrast Agents II, Springer- Verlag, 2002, p. 1-30]. They are favorable in terms of their biocompatibility, high molar absorption coefficient, or high luminescence quantum yield. The high sensitivity of the optical modality in conjunction with optical contrast agents parallels that of nuclear medicine and permits visualization of organs and tissues without the undesirable effect of ionising radiation. A serious drawback of organic fluorescent dyes is possible agglomeration, which can result in quenching of the luminescence. Moreover, the lifetime of organic fluorescent dyes is limited due to photo bleaching and biochemical reactions.

Therefore, there is a need to design fluorescent contrast media that do not show aggregation in solution, are capable of absorbing or emitting in the optical window of biological tissue, possess desirable photo physical properties, exhibit a high lifetime, and are endowed with tissue-specific targeting capability. A prior art approach is the application of coordination compounds comprising a luminescent lanthanide ion as the metal center and macro cyclic ligands to obtain high stability in aqueous solution. However, the additional coordination of water molecules to the metal center, which is difficult to prevent, reduces the quantum efficiency of these complexes to a large extent and thus reduces sensitivity, especially for emission in the red and IR part of the spectrum.

An alternative approach is the application of semi conducting nanoscale particles (quantum dots), whose absorption and emission bands can be tailored by the particle size and thus can be adapted to the optical window of tissue. However, efficient quantum dots are mostly III/V or II/VI semiconductors, e.g. (Ga₅In)P or (Zn₅Cd)(S, Se), such as disclosed in US6,530,944, which are toxic and limitedly suitable for in-vivo imaging.

Another approach is the application of non-toxic and stable host lattices to design inorganic nanoscale particles [Stouwdam, JW et al., Chem. Mater. 15 (2003) 4604], which are dispersible in water and which can penetrate into tissue and cells. SUMMARY OF THE INVENTION

This invention concerns deep red and NIR emitting materials for use in diagnosis and therapy. Inorganic luminescent nanoscale particles are used for this purpose, which exhibit optical transitions in the visible spectral range, which can be exploited for excitation purposes and which show an emission band or lines in the NIR range, preferably between 650 and 1100 nm.

The present invention is directed towards an NIR-emitting luminescent material comprising a mixed crystal with an inorganic host and a dopant ion, wherein the dopant ion occupies a lattice site of the host lattice and wherein the NIR-emitting luminescent material emits in the range 650 to 1100 nm.

In another embodiment of the invention the NIR-emitting luminescent material is used in medical applications. In more preferred embodiment of the invention the NIR-emitting luminescent material is used in diagnosis and/or imaging.

In a further more preferred embodiment of the invention the NIR-emitting luminescent material is used in hyperthermia therapy of tumours.

Another embodiment of the present invention is a NIR-emitting luminescent material according to the present invention wherein the difference in ion radii of the host ion and the dopant ion is less than 20 %. In a preferred embodiment the differ- rence is less than 15 %, more preferred less than 10 % and most preferred less than 5 %.

In a more preferred embodiment the inorganic host is LaPO₄ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺,Tm³⁺, Er³⁺, Yb³⁺ and Ho 3+

In another more preferred embodiment the inorganic host is Gd2θ3 and the dopant ion is selected from a group comprising Pr , Nd , Eu ,Tm , Er , Yb and

In another more preferred embodiment the inorganic host is Y3AI5O₁₂ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺,Tm³⁺, Er³⁺, Yb³ and Ho³⁺. BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 Optical window of "biological matter".

Fig. 2 Emission spectrum of BaMgAIi₀On: l%Cr (maximum at 695 nm). Fig. 3 Emission spectrum of Y₂θ₃:Pr (maximum at 630 nm).

Fig. 4 Emission spectrum of GcbOsiNd (maximum at 890 nm). Fig. 5 Emission spectrum of Gd₂θ₃:Sm (maximum at 978 nm). Fig. 6 Emission spectrum of Gd₂θ₃:Dy (maximum at 839 nm). Fig. 7 Emission spectrum of Gd₂θ₃:Yb (maximum at 976 nm). Fig. 8 Emission spectrum

(maximum at 1064 nm).

Fig. 9 Emission spectrum OfYsAl₅O^Eu (maximum at 710 nm). Fig. 10 Emission spectrum of YsAl₅O^Yb (maximum at 1025 nm). Fig. 11 Emission spectrum of Lu₃Al₅Oi₂:Eu (maximum at 711 nm). Fig. 12 Emission spectra of Lu₃Al₅Oi₂:Cr upon 160 and 415 nm excitation (maximum at 688 nm).

Fig. 13 Particle size distribution by number of stable Gd2θ3:Nd³⁺ nanoparticles in aqueous solution Fig. 14 Gd2θ3:Nd³⁺ nanoparticles after annealing at 800 ⁰C with a particle size of 25 to 30 nm Fig. 15 Gd2θ3:Nd³⁺ nanoparticles after annealing at 800 ⁰C with a particle size of 25 to 30 nm Fig. 16 Gd2θ3:Nd³⁺ microparticles after annealing at 800 ⁰C with a particle size of about 500 nm - 1 μm

Fig. 17 Gd2θ3:Nd³⁺ microparticles after annealing at 800 ⁰C with a particle size of about 500 nm - 1 μm

Fig. 18 Transmission spectrum of stable Gd2θ3:Nd³⁺ nanoparticles in aqueous medium Fig. 19 Excitation and emission spectra of stable Gd₂θ₃:Nd³⁺ nanoparticles in aqueous medium Fig. 20 LaPO₄ :Nd³⁺ nanoparticles before annealing at 800 ⁰C with a particle size of 10 to 15 nm. Fig. 21 LaPO₄INd³⁺ nanoparticles before annealing at 800 ⁰C with a particle size of 10 to 15 nm. Fig. 22 LaPO₄INd³⁺ nanoparticles after annealing at 800 ⁰C with a particle size of 25 to 30 nm.

Fig. 23 LaPO₄INd³⁺ nanoparticles after annealing at 800 ⁰C with a particle size of 25 to 30 nm.

Fig. 24 Excitation and emission spectra Of LaPO₄INd³⁺ nanopowder

DETAILED DESCRIPTION OF EMBODIMENTS The present invention is directed towards an NIR-emitting luminescent material comprising a mixed crystal with an inorganic host and a dopant ion, wherein the dopant ion substitutes a lattice site of the host lattice and wherein the NIR-emitting luminescent material emits in the range 650 to 1100 nm, preferably in the range of 700 to 1050 nm most preferred in the range of 750 to 1050 nm. Some of the NIR-emitting luminescent materials which are subject to the invention may also emit in different spectral regions, however, common to all these ions is the presence of emission in the NIR region.

It is to be pointed out that in a material according to the present invention the mixed crystals are such that dopant ions replace metal ions of the host lattice at their lattice site. This is in contrast to mixed crystals in which dopant ions occupy spaces in between or otherwise remote from host lattice sites. The latter type of mixed crystals generally shows markedly smaller quantum yields compared to crystals in which dopant ions replace metal ions of the host lattice at their lattice site. Coordination of H₂O molecules results in the absence of luminescence in the red-IR part of the spectrum and for this reason has to be prevented. The advantage of the inorganic luminescent materials according to the present invention is that photo bleaching is not an issue and consequently the operational lifetime of such materials in the body is sufficient.

Further possible applications of the NIR-emitting luminescent material according to the present invention may be, but are not limited to: animal imaging, - tomographic imaging of organ morphology, monitoring of organ functions, cardiovascular imaging, e.g. coronary angiography, atherosclerotic plaques, fluorescence endoscopy, e.g. tumours of the GI tract, lung, bladder, cervix, oral cavity, imaging and therapy of tumours, detection of tumours and other abnormalities by monitoring the blood clearance profile of the material, blood analysis diagnostics, e.g. during dialysis, - in- vitro assays (single or multi-analyte), imaging of ocular diseases, intra operative imaging , e.g., complete resection of tumour margins, imaging of skin abnormalities, e.g. melanoma, BCC, or SCC, optical mammography, e.g. for localisation of breast tumours, - brain imaging, e.g., for determination of brain perfusion and stroke diagnosis.

In order to be usefully applied in biomedical settings, materials which are stable in water at physiological pH value are preferred. Additionally, it is preferred that they are non-toxic. In another embodiment the NIR-emitting luminescent materials are coated by a non-toxic insoluble shell. The materials can for instance be coated by SiC>2 or other inert oxides, such as AI2O3, in order to decrease toxicity and at the same time to enhance the molecule lifetime in living or biological systems. This effect is based on the prevention of agglomeration by surface passivation. In another preferred embodiment the NIR-emitting luminescent materials may be adapt to specifically target materials and structures. Targeting of such materials can be achieved by ligands for biological recognition events, such as but not restricted to antibodies in different forms, peptides, peptidomimetics, aptamers, small molecules or hormones. Such ligands for biological recognition events can be attached to the surface of the materials of the present invention through prior functionalization of their surface with reactive groups, see e.g. J.V. Frangioni, Current Opinion in Chemical Biology, 2003, 7, 626.

Another embodiment of the present invention is an NIR-emitting luminescent material according to the present invention wherein the difference in ion radii of the host ion and the dopant ion is less than 20 %. In a preferred embodiment the difference is less than 15 %, more preferred less than 10 % and most preferred less than 5 %. In a further embodiment of the present invention the inorganic host comprised by the NIR-emitting luminescent material according to the present invention is selected from:

• Carbonates • Oxides

• Fluorides

• Aluminates

• Germanates

• Titanates • Vanadates

• Niobates

• Tantalates

• Molybdates

• Tungstates

In a preferred embodiment of the invention the inorganic host is selected from:

MeO, Ln₂O₃, SiO₂, TiO₂, ZrO₂, HfO₂, ZnS, LnPO₄, LnBO₃, LnB₃O₆, LnMgB₅Oi₀, MeCO₃, Ln₂(CO₃)₂, MeAl₂O₄, MeMgAIi₀Oi₇, LnMgAInOi₉, Al₂O₃, Me₂Al₂O₅, LnAlO₃, MeAl₄O₇, Ln₄Al₂O₉, A₂Al₂O₄, Ln₃Al₅Oi₂, Ln₃Ga₅Oi₂,

Mg₄(Si₅Ge)O_{5 5}F, Mg₂TiO₄, Ln₂(Ti₅Zr₅Hf)₂O₇, Me₂Ln₂TiO₇, MeTiO₃,Ln(V,P,Nb,Ta)O₄, Ln₂(Mo₅W)₃Oi₂, ALn(Mo₅W)₂O₈; wherein Me is selected from Mg, Ca, Sr, Ba, Zn; Ln is selected from Sc, Y, La, Gd, Lu, In; and A is selected from Li, Na, K, Rb, Cs; and whereby the activator is selected from the group comprising Ti²⁺, V³⁺,

- <

T-γτi+ , T

F-_"e 3+ , τR->u 3+ , C no 3+ , C /io 2+ , TIr 3+ , -Nκτi2+ , πPt.2+ , -Pr»r 3+ , _ΛNTdJ3+ , o Sm 3+ ,

T E-*u 3+ , T E-<r 3+ , TTim 2+ , r T-i-1m 3+ , T

In + , O Sn 2 + , T PΛ1b 2+ , T B-»i *3 + .

In a more preferred embodiment the inorganic host is LaPO₄ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺,Tm³⁺, Er³⁺, Yb³⁺ and Ho³⁺. In a preferred embodiment subject of the invention are NIR-emitting luminescent materials comprising the inorganic host is LaPO₄ and the dopant ion is selected from a group comprising Pr , Nd , Eu ,Tm , Er , Yb and Ho and their use for medical applications, especially use for diagnosing as e.g. imaging.

In another more preferred embodiment the inorganic host is Gd2θ3 and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺,Tm³⁺, Er³⁺, Yb³⁺ and Ho³⁺. In a preferred embodiment subject of the invention are NIR-emitting luminescent materials comprising the inorganic host is Gd2θ3 and the dopant ion is selected from a group comprising Pr , Nd , Eu ,Tm , Er , Yb and Ho and their use for medical applications, especially use for diagnosing as e.g. imaging.

In another more preferred embodiment the inorganic host is Y3AI5O12 and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺, Tm³⁺, Er³⁺, Yb³ and Ho³⁺. In a preferred embodiment subject of the invention are NIR-emitting luminescent materials comprising the inorganic host is Y3AI5O12 and the dopant ion is selected from a group comprising Pr , Nd , Eu ,Tm , Er , Yb and Ho and their use for medical applications, especially use for diagnosing as e.g. imaging. In a further more preferred embodiment the inorganic host is AI2O3 and the dopant ion is selected from Ti³⁺ or Cr³⁺. In a preferred embodiment subject of the invention are NIR-emitting luminescent materials comprising the inorganic host is AI₂O₃ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺,Tm³⁺, Er³⁺, Yb³⁺ and Ho³⁺ and their use for medical applications, especially use for diagnosing as e.g. imaging..

In a preferred embodiment of the invention the size of the particles composed of the NIR-emitting luminescent material according to the present invention is in the range from 1 to 100 nm, more preferred 1 to 20 nm.

It is preferred that such luminescent materials should exhibit a sufficiently high quantum efficiency, which is preferably > 5%, more preferably larger than 25 % and most preferably larger than 50 %. The luminescence of materials can be based on band-to-band or charge- transfer mechanisms. The emission should be in a wavelength range for which biological tissues are transmissible.

In general, preferred materials should be line emitters, as quenching due to lattice relaxation is reduced in these, especially at larger wavelengths. Examples are e.g. LaPO4:Nd or Gd2O3:Yb.

Additionally, by using line emitters, optical multiplexing experiments become feasible. Preferred materials have host lattices with low phonon frequencies (ω °= V(f/m)), i.e. encompass weak bonds and heavy ions.

Advantages of the claimed NIR emitters are their higher fluorescence lifetime compared to organic fluorescent dyes and in many cases their relatively narrow emission bands or lines, which might allow analysis of several analytes at the same time by optical multiplexing. Thus, the use of the NIR emitter according to the present invention in multiplexing methods is another subject of the invention.

For materials according to the present invention, the wavelength of luminescence is not dependent on the particle size, but on the specific combination of host lattice and dopant ions.

Excitation of the NIR emitting material can be achieved with X-rays or near UV to NIR light or can also be self-activated by using radio-active nuclides. Accordingly, in another embodiment of the invention the excitation wavelength of the particles is from 380 to 700 nm, more preferred from 550 to 700 nm.

A further embodiment of the present invention is a contrast agent comprising a NIR-emitting luminescent material according to the present invention.

Finally, a preferred embodiment of the present invention is the use of a NIR-emitting luminescent material according to the present invention for in vitro assays. The following examples describe the invention in greater detail but are not limiting to this invention: Example 1 Homogeneous precipitation of Gd₂O₃ :Nd³⁺ nanoparticles (1 to 100 nm) via destabilisation of Ln³⁺-aqua EDTA complexes

Appropriate amounts of the lanthanide acetates, i.e. Gd(CH₃COO)3-H₂O and Nd(CH₃COO)3-H₂O, and an organic stabilizer (e.g. citric acid) are dissolved in water in the presence of a complexing agent (e.g. ammonium EDTA hydrate). The pH value of the obtained transparent solution is increased to pH 10 by addition of an alkaline agent. The alkaline solution is stored at 90⁰C for several hours. Dynamic light scattering measurements of the resulting transparent solution indicates the presence of nanoparticles with a hydrodynamic diameter of around 2 nm (Fig. 13). From this stable colloidal solution nanoparticles can be precipitated by slow evaporation of the solvent and subsequent annealing at 800⁰C. The annealed powder consists of spherical nanoparticles with an average diameter of 25 to 30 nm, which is depicted in their respective SEM images (Fig. 14 and Fig. 15).

For comparison purposes, Gd(CH₃COO)₃ H₂O and Nd(CH₃COO)₃ H₂O are dissolved in water and hydroxides are precipitated from this solution by increasing the pH value to 10. The obtained white suspension is filtered off by a blue band filter, and the separated precipitate is dried and annealed at 800 ⁰C. This yields Gd₂O₃ :Nd³⁺ particles, which differ from those Gd₂O₃ :Nd³⁺ particles made by homogenous precipitation with respect to particle morphology and size (Fig. 16 and Fig. 17). The transmission and emission spectra of Gd₂O₃ :Nd³⁺ nanopowder show the typical absorption and emission peaks OfNd³⁺ ions (Fig. 18 and Fig. 19). Example 2

Homogeneous precipitation OfLaPO₄INd³⁺ nanoparticles via destabilisation of Ln³⁺-Aqua EDTA Complexes Appropriate amounts of lanthanide acetates, i.e. La(CH₃COO)₃-H₂O and

Nd(CH₃COO)₃-H₂O] and an organic stabilizer, e.g. citric acid, are dissolved in water in the presence of a complexing agent, e.g. ammonium EDTA hydrate. After addition of the precipitant (e.g. ammoniumdihydrogenphosphate) the pH value of the obtained transparent solution is increased to 10 by addition of an alkaline agent. The obtained light white and cloudy suspension (gel) is stored at 90 ⁰C for several hours. This yields a white suspension. The precipitate is separated by filtration through a 200 nm filter and drying at 120 ⁰C. SEM images of the dry powder reveal that homogeneous, spherical nanoparticles with a primary particle size of 10 to 15 nm have been formed (Fig. 20 and Fig. 21).

After annealing of the nanopowder at 800 ⁰C SEM images reveal the formation of spherical nanoparticles with a particle size of about 25 to 30 nm (Fig. 22 and Fig. 23).

Furthermore, optical measurements of the annealed nanopowders show the typical excitation and emission spectra for Nd³⁺-doped materials (Fig. 24).

Claims

CLAIMS:

1. NIR-emitting luminescent material comprising a mixed crystal with an inorganic host and a dopant ion, wherein the dopant ion occupies a lattice site of the host lattice and wherein the NIR-emitting luminescent material emits in the range of 650 to l lOO nm.

2. NIR-emitting luminescent material according to claim 1, wherein the differences in ion radii of the host ion and the dopant ion is less than 20 %.

3. NIR-emitting luminescent material according to claims 1 or 2, wherein the inorganic host is selected from:

Carbonates

Oxides

Fluorides - Aluminates

Germanates

Titanates

Vanadates

Niobates - Tantalates

Molybdates

Tungstates

4. NIR-emitting luminescent material according to claims 1 to 3, wherein the inorganic host is selected from:

MeO, Ln₂O₃, SiO₂, TiO₂, ZrO₂, HfO₂, ZnS, LnPO₄, LnBO₃, LnB₃O₆, LnMgB₅Oi₀, MeCO₃, Ln₂(CO₃)₂, MeAl₂O₄, MeMgAIi₀Oi₇, LnMgAInOi₉, Al₂O₃, Me₂Al₂O₅, LnAlO₃, MeAl₄O₇, Ln₄Al₂O₉, A₂Al₂O₄, Ln₃Al₅Oi₂, Ln₃Ga₅Oi₂, Mg₄(Si₅Ge)O_{5 5}F, Mg₂TiO₄, Ln₂(Ti₅Zr₅Hf)₂O₇, Me₂Ln₂TiO₇, MeTiO₃,Ln(V,P,Nb,Ta)O₄, Ln₂(Mo₅W)₃Oi₂, ALn(Mo₅W)₂O₈;

wherein Me is selected from Mg₅ Ca₅ Sr₅ Ba₅ Zn; > Ln is selected from Sc₅ Y₅ La₅ Gd₅ Lu₅ In; and

A is selected from Li₅ Na₅ K₅ Rb₅ Cs; and

whereby the activator is selected from the group comprising Ti²⁺, V³⁺, Cr⁴⁺,

Λ M /rn 5+ , < T-γτi+ , T

F-.e 3+ , τR-_>u 3+ , C no 3+ , C /io 2+ , TIr 3+ , -Nκτi2+ , -Pr»ti2+ , -Pr»r 3+ ,

Sm _3+ , _T E₇u 3+ , _T D-*y 3+ , T E-.r 3+ , rT-pm 2+ , r T-pm 3+ , Λ Y/-bU3+ , Λ Y/-bU2+ , Ύ In + , C S_n2+ , T PVbU2+ , τ B>;i3+ .

5. NIR-emitting luminescent material according to claims 1 to 4, wherein the inorganic host is LaPO₄ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺Jm³⁺, Er³⁺, Yb³⁺ and Ho³⁺.

6. NIR-emitting luminescent material according to claims 1 to 4, wherein the inorganic host is Gd₂θ3 and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺Jm³⁺, Er³⁺, Yb³⁺ and Ho³⁺.

7. NIR-emitting luminescent material according to claims 1 to 4, wherein the inorganic host is Y3Al₅Oi₂ and the dopant ion is selected from a group comprising Pr³⁺, Nd³⁺, Eu³⁺Jm³⁺, Er³⁺, Yb³ and Ho³⁺.

8. NIR-emitting luminescent material according to claims 1 to 4, wherein the inorganic host is Al₂θ3 and the dopant ion is selected from Ti³⁺ or Cr³⁺.

9. NIR-emitting luminescent material according to claims 1 to 8, wherein the size of the particles composed of the NIR-emitting luminescent material is in the range from 1 to 100 nm.

10. NIR-emitting luminescent material according to claims 1 to 9, wherein the size of the particles composed of the NIR-emitting luminescent material is in the range from 1 to 20 nm

11. NIR-emitting luminescent material according to claims 1 to 10, wherein the excitation wavelength of the particles is from 380 to 700 nm.

12. NIR-emitting luminescent material according to claims 1 to 11, wherein the excitation wavelength of the particles is from 550 to 700 nm.

13. NIR-emitting luminescent material according to any of claims 1 to 12 for use in medical applications.

14. NIR-emitting luminescent material according to any of claims 1 to 12 for use in diagnosis.

15. NIR-emitting luminescent material according to any of claims 1 to 12 for use in imaging.

16. NIR-emitting luminescent material according to any of claims 1 to 12 for use in hyperthermia therapy of tumours.

17. Contrast agent comprising a NIR-emitting luminescent material according to any of claims 1 to 15.

18. Use of a NIR-emitting luminescent material according to claims 1 to 15 for in vitro assays.