In-vivo diagnostic method by means of near infrared radiation
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. A cyanine dye as represented by the general formula V:
wherein
Q is a fragment selected from the group consisting of
where R 30 represents a hydrogen atom, a hydroxy group, a carboxy group, an alkoxy residue containing 1 to 4 carbon atoms or a chlorine atom, b is an integer 2 or 3, R 31 represents a hydrogen atom or an alkyl residue containing 1 to 4 carbon atoms,
X and Y independently represent an —O—, —S—, —CH═CH— or —C(CH 2 R 32 )(CH 2 R 32 )— fragment each,
R 20 to R 29 , R 32 and R 33 independently represent a hydrogen atom, a hydroxy group, a carboxy-, a sulfonic acid residue or a carboxyalkyl-, alkoxycarbonyl or alkoxyoxoalkyl residue containing up to 10 C atoms or a sulfoalkyl residue containing up to 4 C atoms, or a non-selectively bonding macromolecule or a residue of the general formula VI
—(O) v —(CH 2 ) o —CO—NR 34 —(CH2) s —(NH—CO) q —R 35 (VI)
on the condition that, where X and Y are O, S, —CH═CH— or —C(CH 3 ) 2 — at least one of the residues R 20 to R 29 corresponds to a non-selectively bonding macromolecule or a compound of the general formula VI, where
o and s equal 0 or independently represent an integer between 1 and 6,
q and v independently represent 0 or 1, R 34 represents a hydrogen atom or a methyl residue, R 35 represents an alkyl residue containing 3 to 6 C atoms and comprising 2 to n−1 hydroxy groups, with n being the number of C atoms, or an alkyl residue containing 1 to 6 C atoms that carries 1 to 3 additional carboxy groups, an aryl residue containing 6 to 9 C atoms or arylalkyl residue containing 7 to 15 C atoms, or a residue of the general formula IIId or IIIe
on the condition that q is 1,
or a non-selectively bonding macromolecule,
or R 20 and R 21 , R 21 and R 22 , R 22 and R 23 , R 24 and R 25 , R 25 and R 26 , and/or R 26 and R 27 , together with the interspersed carbon atoms, form a 5- or 6-member aromatic or saturated annelled ring,
and its physiologically tolerable salts.
2. An agent for in-vivo diagnosis comprising the cyanine dye according to claim 1 together with physiologically acceptable adjuvants, substrates, and/or diluents.
3. A method of diagnosing tumours tissue comprising administering the cyanine dye claimed in claim 1 , irradiating the tumours tissue with light in the visible to near infrared range and recording fluorescent radiation produced form the cyanine dye.