Radioactive transition metal-imido hetero-diphosphine complexes, their preparation and radiopharmaceutical compositions thereof

A radioactive transition metal-imido hetero-diphosphine complex compound of formula (I):

• [(Me═N—R)L1L2]+Z− (I),
• wherein:
• Me is a radioactive transition metal selected from the group consisting of 99mTc, 186Re, 188Re;
• R is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, octyl, decyl, dodecyl, propenyl, butenyl, pentenyl, phenyl, benzyl, tolyl, 4-methoxy-benzyl, 4-ethoxy-benzyl, and salicyl, wherein R is substituted with a biologically active substance, said substance being a catecholamine selected from the group consisting of dopamine, L-DOPA, 3-hydroxytyramine, optionally conjugated, via peptide bond, to another biologically active substance selected from the group consisting of sugars, amino acids, fatty acids, vitamins, hormones, peptides, and catecholamines;
• L1 is a tridentate hetero-diphosphine ligand of formula (II):
• wherein:
• R1, R2, R3 and R4, which may be the same or different, are:
• a C1-C15 linear or branched alkyl or alkenyl residue optionally interrupted by —O—, —S—, —N(R′)—, where R′═H or C1-C6 alkyl, and/or optionally substituted with halogen, hydroxy, C1-C5 alkoxy, carboxy, ester, thiol, primary or secondary amino or amido, groups, or
• a phenyl or an aryl residue, R1, R2, R3 and R4 being optionally substituted with a biologically active substance, wherein said biologically active substance is selected among sugars, amino acids, fatty acids, vitamins, hormones, peptides and catecholamines, said catecholamines being optionally conjugated, via peptidic bond, to another of the above mentioned biologically active substances;
• X is oxygen, sulphur, NR5, wherein
• R5is:
• hydrogen,
• a C1-C15 linear or branched alkyl or alkenyl residue optionally interrupted by —O—, —S—, —N(R′)—, where R′═H or C1-C6 alkyl, and/or optionally substituted with halogen, hydroxy, C1-C5 alkoxy, carboxy, ester, thiol, primary or secondary amino or amido groups, or
• a phenyl or an aryl residue, R5 being optionally substituted with a biologically active substance, wherein said biologically active substance is selected among sugars, amino acids, fatty acids, vitamins, hormones, peptides, catecholamines, said catecholamines being optionally conjugated, via peptidic bond, to another of the above mentioned biologically active substances;
• n is an integer ranging from 1 to 5;
• L2 is a bidentate ligand, which comprises a combination of two donor atoms, selected from the group consisting of oxygen, sulphur and nitrogen, said atoms being preferably negatively charged and being separated by a spacer of 2 to 4 members, said spacer being an aliphatic chain or part of an aromatic ring, L2 being optionally conjugated to a biologically active substance as above defined;
• Z− is a mononegative counter-ion selected from the group consisting of Cl−, Br−, OH−, ClO4−, EtO−, tetrafluoroborate.