Optical diagnostic and therapeutic agents and compositions
4 Assignments
0 Petitions
Accused Products
Abstract
Cyanine and indocyanine dye compounds and bioconjugates are disclosed. The present invention includes several cyanine and indocyanine dyes, including bioconjugates of the same, with a variety of bis- and tetrakis (carboxylic acid) homologues. The compounds of the invention may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of compounds of the invention allows favorable delivery to tumor cells as compared to larger molecular weight imaging agents. Further, use of a biocompatible organic solvent such as dimethylsulfoxide may be said to assist in maintaining the fluorescence of compounds of the invention. The compounds and bioconjugates herein disclosed are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, localized therapy, photoacoustic tumor imaging, detection and therapy, and sonofluorescence tumor imaging, detection and therapy.
-
Citations
29 Claims
- 1. A compound of the following general formula, wherein:
- 15. A diagnostic and/or therapeutic composition comprising a compound of the following general formula and at least one of a pharmaceutical carrier, excipient, and buffer, wherein:
-
20. A method of performing a diagnostic or therapeutic procedure comprising:
-
administering to an individual an effective amount of a composition including an compound of the following general formula, wherein;
W3 and X3 may be the same or different and are selected from the group consisting of —
CR1R2, —
O—
, —
NR3, —
S—
, and —
Se;
Y3 is selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C20 aryl, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, C1-C10 aminoalkyl, —
CH2(CH2OCH2)b—
CH2—
OH, —
(CH2)a—
CO2H, —
(CH2)a—
CONH-Bm, —
CH2—
(CH2OCH2)b—
CH2—
CONH-Bm, —
(CH2)a—
NHCO-Bm, —
CH2—
(CH2OCH2)b—
CH2—
NHCO-Bm, —
(CH2)a—
N(R3)—
(CH2)b—
CONH-Bm, —
(CH2)b—
N(R3)—
(CH2)a—
NHCO-Bm, (CH2)a—
N(R3)—
CH2—
(CH2OCH2)b—
CH2—
CONH-Bm, (CH2)a—
N(R3)—
CH2—
(CH2OCH2)b—
CH2—
NHCO-Bm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
(CH2)a—
CONH-Bm, —
CH2—
(CH2CH2)b—
CH2—
N(R3)—
(CH2)a—
NHCO-Bm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
CH2—
(CH2OCH2)d—
CONH-Bm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
CH2—
(CH2OCH2)d—
NHCO-Bm, —
(CH2)a—
NR3R4, and —
CH2(CH2OCH2)b—
CH2NR3R4;
Z3 is selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C20 aryl, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, C1-C10 aminoalkyl, —
CH2(CH2OCH2)b—
CH2—
OH, —
(CH2)a—
CO2H, —
(CH2)a—
CONH-Dm, —
CH2—
(CH2OCH2)b—
CH2—
CONH-Dm, —
(CH2)a—
NHCO-Dm, —
CH2—
(CH2OCH2)b—
CH2—
NHCO-Dm, —
(CH2)a—
N(R3)—
(CH2)b—
CONH-Dm, (CH2)a—
N(R3)—
(CH2)c—
NHCO-Dm, —
(CH2)a—
N(R3)—
CH2—
(CH2OCH2)b—
CH2—
CONH-Dm, —
(CH2)a—
N(R3)—
CH2—
(CH2OCH2)b—
CH2—
NHCO-Dm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
(CH2)a—
CONH-Dm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
(CH2)a—
NHCO-Dm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
CH2—
(CH2OCH2)d—
CONH-Dm, —
CH2—
(CH2OCH2)b—
CH2—
N(R3)—
CH2—
(CH2OCH2)d—
NHCO-Dm, —
(CH2)a—
NR3R4, and —
CH2(CH2OCH2)b—
CH2NR3R4;
A1 is a single or a double bond;
B1, C1, and D1 may be the same or different and are selected from the group consisting of —
O—
, —
S—
, —
Se—
, —
P—
, —
CR1R1, —
CR1, alkyl, NR3, and —
C═
O;
A1, B1, C1, and D1 may together form a 6- to 12-membered carbocyclic ring or a 6- to 12-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom;
a3 and b3 independently vary from 0 to 5;
R1 to R4, and R29 to R37 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, C5-C20 aryl, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, C1-C10 aminoalkyl, glucose derivatives of R groups, cyano, nitro, halogen, saccharide, peptide, —
CH2(CH2OCH2)b—
CH2—
OH, —
(CH2)a—
CO2H, —
(CH2)a—
CONH-Bm, —
CH2—
(CH2OCH2)b—
CH2—
CONH-Bm, —
(CH2)a—
NHCO-Bm, —
CH2—
(CH2OCH2)b—
CH2—
NHCO-Bm, —
(CH2)a—
OH and —
CH2—
(CH2OCH2)b—
CO2H;
Bm and Dm are independently selected from the group consisting of a peptide, a protein, a cell, an antibody, an antibody fragment, a saccharide, a glycopeptide, a peptidomimetic, a drug, a drug mimic, a hormone, a metal chelating agent, a radioactive or nonradioactive metal complex, a photosensitizer, and an echogenic agent;
a and c are independently from 1 to 20; and
b and d are independently from 1 to 100. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29)
-
Specification