Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors

Abstract

A compound of formula (I): in which R 1 represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C 1 -C 4 )alkyl] 3 group, Ar represents an aryl group or a heteroaryl group, R 9 represents a hydrogen atom, a (C 1 -C 4 ) alkyl group or forms together with the group R 1 —Ar a ring fused with the Ar group, A represents a group of formula (β) or (δ): R 3 and R 4 independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 ) alkenyl group or a group of formula (y): wherein R 11 represents an optionally labelled halogen, a radionuclide, an aryl or heteroaryl group optionally substituted by an optionally labelled halogen, a radionuclide, a —NO 2 group, a —NR 5 R 6 group, a N + R 5 R 6 R 7 X − group, or a —OSO 2 R 12 group, and their addition salts with pharmaceutically acceptable acids.

1 . Compound of formula (I): 
       
         
           
           
               
               
           
         
         in which 
         R 1  represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C 1 -C 4 )alkyl] 3  group, 
         Ar represents an aryl group or a heteroaryl group, it being possible for the said aryl or heteroaryl group to be mono or disubstituted by:
 an optionally labelled halogen, 
 a hydroxy group, 
 a (C 1 -C 4 )alkyl group, 
 a (C 1 -C 8 )alkoxy group, 
 a —NO 2  group, 
 an oxo group, 
 a —NR 5 R 6 , —N + R 5 R 6 R 7 X − , —NHCO 2 R 8 , —NHCOR 8 , —CONHR 8 , —NHCONHR 8 , —SR 8 , —COR 8 , —CO 2 R 8  or —SO 2 R 8  group, 
 an aryl or an arylalkyl group, or 
 a Sn[(C 1 -C 4 )alkyl] 3  group, 
 
         R 5 , R 6  and R 7  independently represent a hydrogen atom, a (C 1 -C 4 )alkyl group, an aryl group or an arylalkyl group, 
         X −  represents a monovalent anion, a sulphate, a halide, an iodide, or a triflate, 
         R 8  represents a hydrogen atom, a (C 1 -C 8 )alkyl group, an aryl group or an arylalkyl group, 
         R 9  represents a hydrogen atom, a (C 1 -C 4 )alkyl group or forms together with the group R 1 —Ar a ring fused with the Ar group, forming the following bicyclic ring: 
       
       
         
           
           
               
               
           
         
         wherein Q is a (CH 2 ) p  group or a —CO— group and p is an integer ranging from 1 to 3, the bond between R 1 —Ar and Q being bound to Ar in ortho position from the bond between Ar and the remaining structure, the obtained structure corresponding to the following phthalimide formula (α): 
       
       
         
           
           
               
               
           
         
         wherein R 1  is as defined above, and R 3 , R 4  and A are as defined below; 
         A represents a group of formula (β) or (δ): 
       
       
         
           
           
               
               
           
         
         wherein
 t is an integer ranging from 2 to 4, 
 m is an integer ranging from 0 to 4, 
 n is an integer ranging from 0 to 4, 
 D is selected from —(CH 2 ) x —, —O—, —NH—, —S—, —SO 2 —, —CONH—, —NHCO—, —CO 2 — and —NHCO 2 —, wherein x is a integer ranging from 0 to 4, 
 G is selected from —(CH 2 ) x —, —O—, —NH—, —S—, —SO 2 —, —NHCO—, —CO 2 — and —NHCO 2 —, wherein x is a integer ranging from 0 to 4, 
 R 10  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group, a —N + R 5 R 6 R 2 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined above, 
 
         R 3  and R 4  independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkenyl group or a group of formula (γ):
   —Y—Z—W—R 11   (γ)
 
 
         wherein 
         Y, Z, W independently represent
 (i) a bond, 
 (ii) a (C 1 -C 8 )alkylene group, a (C 2 -C 10 )alkenylene group, a (C 2 -C 10 )alkynylene group, or 
 (iii) a group selected from —O—, —NH—, —S—, —SO 2 —, —CO—, —CO 2 —, —CONH—, —NHCO— and —NHCO 2 —, 
 
         with the proviso that at most one of Y, Z, W has the above definition (iii), 
         R 11 , represents
 an optionally labelled halogen, 
 a radionuclide, 
 an aryl or heteroaryl group optionally substituted by an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group, or a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined above, or 
 a —OSO 2 R 12  group, wherein R 12 , is a (C 1 -C 6 )alkyl group, a (C 3 -C 8 )cycloalkyl, an aryl group or a heteroaryl group, wherein said alkyl, cycloalkyl, aryl or heteroaryl groups are optionally substituted by 1 to 3 group(s) chosen among a halogen, a (C 1 -C 4 )alkyl group, a —NO 2  group, a —CN group or a —NR 5 R 6  group, where R 5  and R 6  are as defined above, 
 
         and their addition salts with pharmaceutically acceptable acids, 
         wherein said precursor group is chosen among a —NO 2  group, a halogen with the exclusion of fluorine, a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined above, when said precursor group is linked to an aryl or heteroaryl group and among a halogen with the exclusion of fluorine, or a —OSO 2 R 12  group, wherein R 12  is a (C 1 -C 6 )alkyl group, a (C 3 -C 8 )cycloalkyl, an aryl group or a heteroaryl group, wherein said alkyl, cycloalkyl, aryl or heteroaryl groups are optionally substituted by 1 to 3 group(s) chosen among a halogen, a (C 1 -C 4 )alkyl group, a —NO 2  group, a —CN group or a —NR 5 R 6  group, where R 5  and R 6  are as defined above when said precursor group is linked to alkyl, alkenyl, alkynyl, alkylene, alkenylene or alkynylene group. 
         with the proviso that:
 the compound of formula (I) comprises at least one optionally labelled fluorine atom or a precursor group thereof, and 
 the R 1 —Ar group comprises at least an optionally labelled halogen or a radionuclide other than an optionally labelled fluorine atom or said previous precursor group thereof. 
 
       
     
     
         2 . Compound of formula (I) according  claim 1 , wherein when Ar is a phenyl group, at least one of the R 3  and R 4  groups represents a group of formula (ε) 
       
         
           
           
               
               
           
         
         wherein
 m and D are as defined in  claim 1 , and 
 R 14  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined in  claim 1 ; 
 
         and wherein Ar is different from a phenyl group. 
       
     
     
         3 . Compound according to  claim 1 , wherein the following conditions are fulfilled separately or simultaneously:
 Ar represents a group selected from naphthyl, anthryl, pyridyl, quinoxalinyl, quinolyl, isoquinolyl, imidazopyridyl, naphthyridinyl, acridinyl, acridonyl and phenazinyl, it being possible for said group to be monosubstituted by a methyl group, a methoxy group or an optionally labelled halogen,   R 9  is a hydrogen atom,   A is a (β) group as defined in  claim 1 , wherein t is 2,   R 3  and R 4  independently represent a hydrogen atom, a (C 1 -C 4 )alkyl group,
   —Y—Z—W—R 11   (γ),
 
   
       a group
 wherein 
 Y, Z and W independently represent 
 (i) a bond, 
 (ii) a (C 1 -C 4 )alkylene group, a (C 2 -C 10 )alkenylene group or a (C 2 -C 10 )alkynylene group, or 
 (iii) a group selected from —O—, —NH—, —CONH— and —NHCO— 
 with the proviso that at most one of Y, Z, W has the above definition (iii), and 
 R 11  represents
 an optionally labelled halogen, 
 a 
 
 
       
         
           
           
               
               
           
         
         
            group, wherein R 13  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined in  claim 1 . 
         
       
     
     
         4 . Compound of formula (Ib), 
       
         
           
           
               
               
           
         
         in which 
         R 1  represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C 1 -C 4 )alkyl] 3  group and A represents a group of formula (β) or (δ): 
       
       
         
           
           
               
               
           
         
         Ar represents an aryl or a heteroaryl group, 
         R 2  is chosen among an optionally labelled halogen, a radionuclide, a hydroxy group, a (C 1 -C 4 )alkyl group, a (C 1 -C 8 )alkoxy group, a —NO 2  group, an oxo group, a —NR 5 R 6  group, a —N + R 5 R 6 R 7 X −  group, a —NHCO 2 R 8  group, a —NHCOR 8  group, a —CONHR 8  group, a —NHCONHR 8  group, a —SR 8  group, a —COR 8  group, a —CO 2 R 8  group, a —SO 2 R 8  group, an aryl group or a —Sn[(C 1 -C 4 )alkyl] 3  group, 
         R 5 , R 6  and R 7  independently represent a hydrogen atom, a (C 1 -C 4 )alkyl group, an aryl group or an arylalkyl group, 
         X −  represents a monovalent anion, a sulphate, a halide, an iodide, or a triflate, and 
         R 8  represents a hydrogen atom, a (C 1 -C 8 )alkyl group, an aryl group or an arylalkyl group, 
         R 3  and R 4  independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkenyl group or a group of formula (ε) or (φ) 
       
       
         
           
           
               
               
           
         
         wherein: 
         m is an integer ranging from 0 to 4, 
         D is selected from —(CH 2 ) x —, —O—, —NH—, —S—, —CONH—, —NHCO—, —CO 2 — and —NHCO 2 — wherein x is a integer ranging from 0 to 4, 
         R 14  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6  and R 7  independently represent a hydrogen atom, a (C 1 -C 4 )alkyl group, an aryl group or an arylalkyl group and X −  is as defined above, 
         q and r are integers and independently ranging from 0 to 8, 
         T represents a bond, a (C 1 -C 4 )alkylene group, a (C 2 -C 10 )alkenylene group or a (C 2 -C 10 )alkynylene group, and 
         R 15  represents
 an optionally labelled halogen, 
 a radionuclide, 
 a —OSO 2 R 12  group, wherein R 12  is a (C 1 -C 6 )alkyl group, a (C 3 -C 8 )cycloalkyl, an aryl group or a heteroaryl group, wherein said alkyl, cycloalkyl, aryl or heteroaryl groups are optionally substituted by 1 to 3 group(s) chosen among a halogen, a (C 1 -C 4 )alkyl group, a —NO 2  group, a —CN group or a—NR 5 R 6  group, where R 5  and R 6  are as defined above, 
 
         and their addition salts with pharmaceutically acceptable acids, 
         with the proviso that:
 the compound of formula (Ib) comprises at least one optionally labelled fluorine atom or a precursor group thereof, and 
 the R 1 —Ar group comprises at least an optionally labelled halogen or a radionuclide other than an optionally labelled fluorine atom or said previous precursor group thereof. 
 
       
     
     
         5 . Compound of formula (Ib), according to  claim 4 , wherein the aryl or heteroaryl group is chosen from a pyridyl, a quinolyl, isoquinolyl, quinoxalinyl, acridinyl, acridonyl, phenazinyl, naphthyl, naphthyridinyl and imidazopyridyl. 
     
     
         6 . Compound of formula (Ib) according to  claim 4 , wherein the following conditions are fulfilled separately or simultaneously:
 Ar represents a group selected from naphthyl, anthryl, pyridyl, quinoxalinyl, quinolyl, imidazopyridyl, naphthyridinyl, acridinyl, acridonyl and phenazinyl, it being possible for said group to be monosubstituted by a methyl group, a methoxy group or an optionally labelled halogen,   A is a (β) group as defined in  claim 4  wherein t is 2,   R 3  and R 4  independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 )alkenyl group or a group of formula (ε) or (φ)   
       
         
           
           
               
               
           
         
         wherein 
         m is as defined above, 
         D is —(CH 2 ) x —, —O—, —NH—, —CONH—, —NHCO—, 
         x ranges from 0 to 2, 
         R 14  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group or a —N 4 R 5 R 6 R 7 X −  group, wherein X −  is as defined in  claim 4 , 
         R 5 , R 6  and R 7  are a hydrogen atom or a (C 1 -C 4 )alkyl group, 
         q and r are integers and independently ranging from 0 to 3, 
         T represents a bond, a (C 1 -C 4 )alkylene group, a (C 2 -C 10 )alkenylene group or a (C 2 -C 10 )alkynylene group, and 
         R 15  represents an optionally labelled halogen, a radionuclide, or a —OSO 2 R 12  group, wherein R 12  is a trifluoromethyl group, a toluoyl group, a bromophenyl group, a nitrophenyl group or a methyl group. 
       
     
     
         7 . Compound of formula (Ib), according to  claim 4 , wherein Ar represents a group selected from naphthyl, anthryl, pyridyl, quinoxalinyl, quinolyl, imidazopyridyl, naphthyridinyl, acridinyl, acridonyl and phenazinyl, optionally said group is monosubstituted by a methyl group, a methoxy group or an optionally labelled halogen; and
 wherein:
 when A represents a group of formula (β) as defined in  claim 4 , 
 either at least one of the R 3  and R 4  groups represents a group of formula (ε) or (φ) 
   
       
         
           
           
               
               
           
         
         wherein 
         m, D, q, T, and r are as defined in  claim 4 , and 
         R 14  and R 15  represent an optionally labelled fluorine atom or a precursor group thereof;
 or R 3  and R 4  represent a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkenyl group, and the optionally labelled fluorine atom or a precursor group thereof; 
 when A represents a group of formula (δ) as defined in  claim 1 , 
 
         R 10  represents an optionally labelled fluorine atom or a precursor group thereof. 
       
     
     
         8 . Compound according to  claim 4 , wherein the compound is of formula (Ic) 
       
         
           
           
               
               
           
         
         in which A is (CH 2 ) t    
         Ar is chosen from pyridyl, quinolyl, isoquinolyl, quinoxalinyl, acridinyl, acridonyl, phenazinyl, naphthyl, naphthyridinyl and imidazopyridyl, 
         R 1  is an optionally labelled iodine atom, 
         R 2  represents a hydrogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy group, an optionally labelled halogen, an —SH group, an —OH group, an —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein X −  is as defined in  claim 4  and wherein R 5 , R 6  and R 7  can independently represent a hydrogen atom or a (C 1 -C 4 )alkyl group, 
         t is as defined above, 
         R 3  and R 4  represent the formula (φ)
   —(CH 2 ) q -T—(CH 2 ) r —R 15   (φ)
 
 
         wherein 
         q and r are integers and independently ranging from 0 to 4, 
         T represents a bond, (C 1 -C 4 )alkylene group, a (C 2 -C 10 )alkenylene group or a (C 2 -C 10 )alkynylene group or a group selected from —O—, —NH—, —CONH— and 
         R 15  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, 
         a —SO 2 R 12  group wherein R 12  is as defined in  claim 4  or a 
       
       
         
           
           
               
               
           
         
          group, wherein R 13  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein X −  is as defined in  claim 4  and wherein R 5 , R 6  and R 7  are as defined in  claim 4 , 
         with the proviso that the compound of formula (Ic) comprises at least one optionally labelled fluorine atom or a precursor group thereof, the R 1 —Ar group comprises at least an optionally labelled halogen atom or a radionuclide other than said previous optionally labelled fluorine atom or said previous precursor group thereof, 
         and their addition salts with pharmaceutically acceptable acids. 
       
     
     
         9 . Compound of formula (Ic) according to  claim 8 , wherein t is equal to 2 or 4. 
     
     
         10 . Compound of formula (Id) 
       
         
           
           
               
               
           
         
         in which:
 Ar is chosen from pyridyl, quinolyl, isoquinolyl, quinoxalinyl, acridinyl, acridonyl, phenazinyl, naphthyl, naphthyridinyl and imidazopyridyl, 
 R 1  is an optionally labelled iodine atom, 
 R 2  represents a hydrogen atom, a (C 1 -C 4 )alkyl group, a (C 1 -C 4 )alkoxy group, an optionally labelled halogen, an —SH group, an —OH group, an —NR 5 R 6  group or a —N + R 5 R 6 R 7 X −  group, wherein X −  represents a monovalent anion, a sulphate, a halide, an iodide, or a triflate, and wherein R 5 , R 6  and R 7  independently represent a hydrogen atom or a (C 1 -C 4 )alkyl group, 
 R 3  and R 4  independently represent a (C 1 -C 6 )alkyl group or (C 1 -C 6 )alkenyl group, 
 m and n are integers independently ranging from 0 to 4, 
 R 10  represents a hydrogen atom, an optionally labelled halogen, a radionuclide, a —NO 2  group, a —NR 5 R 6  group, a —N + R 5 R 6 R 7 X −  group, wherein R 5 , R 6 , R 7  and X −  are as defined above, 
 
         with the proviso that the compound of formula (Id) comprises at least one optionally labelled fluorine atom or precursor group thereof, and that the R 1 —Ar group comprises at least an optionally labelled halogen or a radionuclide other than said previous optionally labelled fluorine atom or said previous precursor group thereof, 
         and their addition salts with pharmaceutically acceptable acids. 
       
     
     
         11 . A radiolabelled compound according to  claim 1 , wherein said radiolabelling occurs by means of a radionuclide which is a radioisotope chosen from iodine-123, iodine-124, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77, fluorine-18, astatine-210 or astatine-211. 
     
     
         12 . A radiolabelled compound according to  claim 1  wherein R 1  is an iodine atom chosen from iodine-123, iodine-125 and iodine-131. 
     
     
         13 . Compound according to  claim 1 , chosen from:
 N-[2-N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-ethyl-N-(2-[(6-fluoropyridin-2-yl)amino]ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[[N-ethyl-N-(6-fluoropyridin-2-yl)]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[[N-ethyl-N-(2-fluoroethyl)]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[[N-ethyl-N-(2-fluoropyridin-4-yl)methyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-ethyl-N-[2-[[(2-fluoropyridin-4-yl)carbonyl]amino]ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[[N-ethyl-N-2-(2-fluoropyridin-4-yl)ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[[N-ethyl-N-3-(2-fluoropyridin-4-yl)propyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-ethyl-N-((E)-4-fluorobut-2-enyl)]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-nitropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-[2-[(6-bromopyridin-2-yl)amino]ethyl]-N-(ethyl)amino]ethyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoquinoline-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodonaphthalene-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-8-iodo-[1,6]naphthyridine-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-6-iodoimidazo[1,2-a]pyridine-2-carboxamide,   N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-7-iodoacridone-4-carboxamide,   N-[2-(N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]-7-iodophenazine-1-carboxamide,   N-[[4-(N,N-diethylaminomethyl)-2-fluoropyridin-3-yl]methyl]-6-iodoquinoxaline-2-carboxamide,   N-[2-(diethylamino)ethyl]-4-fluoro-6-iodoquinoline-3-carboxamide,   N-[2-(diethylamino)ethyl]-4-fluoro-6-iodoquinoline-8-carboxamide,   N-[2-(diethylamino)ethyl]-4-fluoro-6-iodoquinoline-2-carboxamide,   N-[2-(diethylamino)ethyl]-2-fluoro-6-iodoquinoline-4-carboxamide,   and their pharmaceutically acceptable salts.   
     
     
         14 . Process for the preparation of the compound of formula (I) according to  claim 1 , comprising the step of condensation of a compound according to the general formula (IIa) or (IIb) 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2  and Ar are as defined in  claim 1 , 
         R 16  is a —OH group, a halogen, a —OR 17  group or a −OCOR 18  group, 
         wherein 
         R 17  is a (C 1 -C 6 )alkyl, an aryl or heteroaryl group selected from benzene, pentafluorobenzene, p-nitrobenzene, triazole, benzotriazole, 7-azabenzotriazole and succinimide or a (C 1 -C 4 )alkyl, or a p-nitrophenyl group, 
         R 18  is a (C 1 -C 6 )alkyl, an aryl or a (C 1 -C 4 )alkoxy group, 
         with a diamine, according to the general formula (III)
   H 2 N-A-NR 3 R 4   (III)
 
 
         wherein: 
         A, R 3  and R 4  are as defined in  claim 1 . 
       
     
     
         15 . Compounds of formula (III) as defined in  claim 14 , including the compounds of formula (III) containing a protective group on the primary amine, wherein A, R 3  and R 4  are as defined in  claim 14 , and wherein
 A is   
       
         
           
           
               
               
           
         
          and at least one optionally labelled fluorine atom or a precursor group thereof, is located on said group, or 
         at least one of the R 3  and R 4  groups represents a group of formula (ε) 
       
       
         
           
           
               
               
           
         
          and at least one optionally labelled fluorine atom or a precursor group thereof is located on said group. 
       
     
     
         16 . Radiopharmaceutical composition comprising, as active principle, a radiolabelled compound of formula (I) or one of its pharmaceutically acceptable salts as defined according to  claim 1 . 
     
     
         17 . A method for the diagnosis and/or for the treatment of melanoma, the method comprising:
 providing a radiolabelled compound of formula (I), as defined according to  claim 1 .   
     
     
         18 . A method for the preparation of a composition for the diagnosis and/or the treatment of melanoma, the method comprising:
 administering an effective amount of a compound of formulae (I), as defined according to  claim 1 .