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US 6,258,340 B1Granted
In-vivo diagnostic method by near infrared radiation
AssigneesInstitut fur Diagnostikforschung GmbH, der Freien Universitat Berlin
InventorsKai Licha, Björn Riefke, Wolfhard Semmler, Ulrich Speck, Christoph-Stephan Hilger
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Abstract
This invention relates to a in-vivo diagnostic method based on near infrared ra ation (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.
Claims3
An in-vivo diagnostic near infrared radiation method comprising:
- (a) administering a compound of the general formula I
- B1—(F—Wn)m (I)
- wherein
- 1 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;
- W represents a hydrophilic group that improves water-solubility, with n-octanol-water distribution coefficient of the compound according to formula I being less than or equal to 2.0 for 1=0;
- as well as a physiologically tolerable salt;
- (b) irradiating the compound with light in the near infrared range;
- and
- (c) recording the radiation produced by the compound, wherein F represents a cyanine dye of the general formula IIa
- wherein
- r represents the numbers 0, 1 or 2, wherein, for r=2, the respective L6 and L7 groups that occur in duplicate is the same or different,
- L1 to L7 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, 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 L1 to L7, or two of L1 to L7 that are linked via a —CO— group,
- R3 to R12 are the same or different, each independently representing a hydrogen atom, a group B or W, or an alkyl or alkenyl group containing up to 6 carbon atoms or an aryl or aralkyl group containing up to 9 carbon atoms, said alkyl, alkenyl, aryl or aralkyl group, optionally carrying an additional group W, or to each pair of adjacent groups R3 to R10 are annealed with due regard for the interspersed C atoms, 5- to 6-member rings that are saturated, unsatured or aromatic, and that optionally carry an additional group R, and
- X and Y are the same or different, each independently representing an O, S, Se or Te or a —C(CH3)2—, —CH═CH— or —CR13R14— group,
- where R13 and R14 independently represent a hydrogen atom, a group B or W, 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.
16 more elements
Dependencies are inferred from the claim text.