Near infrared imaging agent
View Patent ↗This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.
1. An in-vivo diagnostic based on near infrared radiation comprising compounds of the general formula I
B L —(F—W n ) m (I)
wherein
L represents a number from 0 to 6,
n represents a number from 0 to 10, and
m represents a number from 1 to 100;
B is a biological detecting unit having a molecular weight of up to 30,000 that bonds to specific cell populations or selectively to receptors, or accumulates in tissues or tumours, or generally stays in the blood, or is a macromolecule that bonds non-selectively;
F represents a dye showing maximum absorption in the range of 650 to 1200 nm;
as well as their physiologically tolerable salts, wherein F within the general formula I represents a cyanine dye of the general formula IIa
wherein
r represents the numbers 0, 1 or 2, wherein, for r=2, the respective L 6 and L 7 groups that occur in duplicate may be the same or different, L 1 to L 7 are the same or different, each independently representing a CH or CR group,
where
R is a halogen atom, a hydroxy, carboxy, acetoxy, amino, nitro, cyano or sulfonic acid group or an alkyl, alkenyl, hydroxyalkyl, carboxyalkyl, alkoxy, alkoxycarbonyl, sulfoalkyl, alkylamino, dialkylamino or halogenalkyl group containing up to 6 carbon atoms, an aryl, alkylaryl, hydroxyaryl, carboxyaryl, sulfoaryl, arylamino, diarylamino, nitroaryl or halogenaryl group containing up to 9 carbon atoms, or where R represents a bond that bonds to another group R and forms a 4- to 6-member ring together with the interspersed groups L 1 to L 7 , or two of L 1 to L 7 that are linked via a —CO— group,
R 3 to R 12 are the same or different, each independently representing a hydrogen atom, a group B as defined above or W as defined below, or an alkyl or alkenyl group containing up to 6 carbon atoms or an aryl or aralkyl group optionally carrying an additional group W as defined below, or with 5- to 6- member rings that may be saturated, unsaturated or aromatic, and that may optionally carry an additional group R as defined above, annealed to each pair of adjacent residue R 3 to R 10 with due regard for the interspersed C atoms,
X and Y are the same or different, each independently representing an O, S, Se or Te or a —C(CH 3 ) 2— , —CH═CH— or —CR 13 R 14 — group,
where R 13 and R 14 independently represent a hydrogen atom, a group B as defined above or W as defined below, or an alkyl or alkenyl group containing up to 6 carbon atoms or an aryl or aralkyl group containing up to 9 carbon atoms, the alkyl, alkenyl, aryl or aralkyl group optionally carrying an additional group W as defined below,
wherein W within the general formula I is a carboxy or sulfonic acid group or a carboxyalkyl group or an alkoxycarbonyl or alkoxyoxoalkyl group containing up to 12 carbon atoms, and
wherein W takes the position of R 4 and R 8 , R 6 and R 10 , R 11 and R 12 , or combinations thereof.
2. A method of producing a fluorescent image in tissues, the method comprising administering at least one of the compounds of claim 1 to tissues and detecting said compound by means of near infrared radiation.
3. An agent for in-vivo diagnosis comprising at least one of the cyanine dyes according to claim 1 together with common adjuvants, substrates and diluents.