US2022387631A1PendingUtilityA1
Near-infrared fluorescent contrast bioimaging agents and methods of use thereof
Assignee: BETH ISRAEL DEACONESS MEDICAL CT INCPriority: Oct 31, 2013Filed: Jul 9, 2021Published: Dec 8, 2022
Est. expiryOct 31, 2033(~7.3 yrs left)· nominal 20-yr term from priority
C09B 23/0041C09B 23/086C09B 69/008A61K 49/0028G01N 33/4833A61K 49/0032C09B 23/0025C09B 23/0016C09B 23/083A61K 49/0021C09B 23/0066C09B 23/04C09B 23/0033C09B 19/00C09B 17/00A61K 49/003C09B 57/10A61K 49/0017A61K 49/0041A61K 49/006
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Claims
Abstract
The instant invention provides near-infrared fluorescent biological contrast agents and methods of using them.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A near-infrared fluorescent contrast agent according to Formula (I):
Wherein
Each R 1 is independently H, OR′, halogen, sulfonato, substituted or unsubstituted amino, C(O)NH—C 1 -C 6 alkyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or phenyl;
Each R 2 is independently H, OR′, halogen, sulfonato, substituted or unsubstituted amino, C(O)NH—C 1 -C 6 alkyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or phenyl;
Or R 1 and R 2 can be taken together with the carbon atoms to which they are attached to form a 5-6 membered aryl or heteroaryl ring, optionally substituted with halogen, alkyl, alkoxy, hydroxyl, —SO 2 OH, or —CO 2 H;
Each R 3 is independently H, OR′, halogen, sulfonato, substituted or unsubstituted amino, C(O)NH—C 1 -C 6 alkyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or phenyl;
Q is H, alkyl optionally substituted with alkoxy, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —N + (alkyl) 3 , —OCO-alkyl, —SO 2 OH, phenyl, sulfonato, phosphates, KUE, GPI,—or —NR 3 R 4 R 5 , wherein R 3 , R 4 and R 5 are each independently for each occurrence H or C 1 -C 4 alkyl, or R 4 and R 5 , taken together with the nitrogen atom to which they are attached, form a heterocyclic ring;
X and Y are each independently O, S, Se, C(R″) 2 , NR′″;
Z is H, halogen, CN, R 6 , OR 6 , SR 6 , NHR 6 or CH 2 R 6 , in which R 6 is optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or optionally substituted heteroaryl, alkyl-N 3 , aryl-N 3 , aryl-halogen;
Each R′ is independently H, alkyl or aryl;
Each R″ is independently H or alkyl;
Each R′″ is independently H, alkyl, alkyl-SO 3 H, or alkyl-COOH;
m and n are independently an integer from 0-3; and
L is an anion;
or a salt, solvate, hydrate, polymorph, prodrug, or stereoisomer thereof.
2 . The near-infrared imaging agent of claim 1 represented by the formula:
Name
Structure
AL22
SP64
SP60
PTN1
SP56
QBN1
ZK195
YY187
TG42
TG53
LN24
LN15
YY180
NRB1
NRB2
NRB3
ZK190
ZK189
SP59
JM1
SP67
E60
E58
E59
AL27
AL18
AL16
AL25
AL29
AL30
AL33
AL34
AL35
AL36
AL14
AL79
SP27
SP28
SP29
SP30
SP33
SP43
SP49
SP51
SP53
SP79
SP99
SP116
SP117
ZK185
ZK135
QBN14
EAO42
ZK166
PTN13
PTN12
ZK148
ZK154
E72
ZK159
E70
ZK153
PTN11
ZK155
ZK143
ZK140
ZK29
SP34
ZK104
TP1
ZK14
PTN6
LN79
AH34
TP4
LS1
YY163
ZK15
WuA108
ZK150
ZK156
ESS23
AL31
AL43
AL20
TG44
ZK79
ESS13
WuA110
YY161
E71
ZK78
ZK133
ZK23
MDL17
ZK203
ZK204
ZK208
ZK106
ZK124
ZK126
ZK101
ZK172
MDL16
LN37
TG20
LO4
ZK211
ZK214
ZK215
YY190
AL11
AL12
CMI24
CMI26
E16
E17
E24
E27
E36
E37
E38
E39
E43
E44
E45
E50
E51
E77
E78
E79
E80
E81
ES17
ES21
LO1
LO2
LO3
MHI106
MHI128
MHI84
MHI86
MHI96
MHI97
P700H
P700SO3
T14
T17
T18
T20
T23
T24
T25
T27
T29
A20
A21
A80
A100
A104
A106
A134
A138
A146
A148
A149
A150
A160
A161
A24
AC2
AC3
AC8
AN3
SP72
ZK138-2
ZK169
MHI85
SP66
EAO72
EAO76
ZK2565
ZK2615
LN15-NHS
PS127
PS128
PS129
PS130
PS131
PS132
PS133
L700-1A
L700-1C
3 . The near-infrared imaging agent of claim 2 , represented by the formula:
4 . The near-infrared imaging agent of claim 2 , represented by the formula:
5 . A method of imaging tissue, lumens, or cells, the method comprising:
(a) contacting the tissue, lumen, or cells with an imaging agent according to claim 1 ; (b) irradiating the tissue, lumen, or cells at a wavelength absorbed by the compound; {circle around (c)} and detecting a signal from the compound, thereby imaging the tissue, lumen, or cells.
6 . The method of claim 5 , wherein the imaging agent is:
7 . The method of claim 5 , wherein the tissue or cells are blood vessels, lumens, ureters, cartilage, bone, thyroid, parathyroids, adrenal gland, salivary gland, white adipose tissue, brown adipose tissue, ovarian cells, testicular cells, seminal vesicles, prostate, pancreas, spleen, gallbladder, bile ducts, Peyer's patches, brain grey matter, brain white matter, brain vasculature, choroid plexus, cerebrospinal fluid, nerves, thoracic duct, pan lymph nodes, sentinel lymph nodes, vulnerable plaque, stem cells, or neuroendocrine tumors.
8 . The method of claim 5 , wherein the imaging agent is administered to an organism comprising the tissue, lumen, or cells.
9 . The method of claim 8 , wherein the organism is human.
10 . The method of claim 5 , wherein the imaging agent has peak absorbance at about 600 nm to 850 nm.
11 . The method of claim 5 , wherein the tissue or cells is imaged ex vivo.
12 . The method of claim 5 , where the imaging agent further comprises a PEG-moiety.
13 . The method of claim 5 , where the imaging agent further comprises a radioisotope for either single-photon emission computed tomography (SPECT) or positron emission tomography (PET).
14 . The method of claim 5 , wherein the compound comprises a reactive linking group, such as NHS ester, sulfo-NHS ester, or a TFP ester.
15 . The method of claim 5 , wherein the compound comprises a chelator moiety capable of chelating a metal atom.
16 . The method of claim 5 , wherein the chelator moiety is a DOTA, DTPA, HYNIC, or desferoxime, or a derivative thereof.
17 . A method for imaging the sentinel lymph node, the method comprising:
(a) contacting the sentinel lymph node with an imaging agent according to claim 1 ; (b) irradiating the tissue at a wavelength absorbed by the imaging agent; (c) and detecting a signal from the imaging agent, thereby imaging the sentinel lymph node.
18 . The method according to claim 17 , wherein the imaging agent is
and the irradiating wavelength is in the 660-760 nm range.
19 . The method according to claim 17 , wherein the imaging agent is
and the irradiating wavelength is in the 760-800 nm range.Join the waitlist — get patent alerts
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