US2016375157A1PendingUtilityA1
Compositions for targeted imaging and therapy
Est. expiryMar 27, 2027(~0.7 yrs left)· nominal 20-yr term from priority
A61P 35/00A61K 51/1244A61K 51/08A61N 5/10A61K 51/0491A61K 51/0497A61K 51/088A61K 51/0482A61K 51/0493A61K 45/06A61K 51/1248
33
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Claims
Abstract
The present invention relates to the field of radiochemistry, nuclear imaging, radionuclide therapy and chemical synthesis. More particularly, it concerns a strategy for radiolabeling target ligands. It further concerns methods of using those radiolabeled ligands for imaging, radionuclide therapy and tissue-specific disease imaging.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A composition, comprising:
a TA2S derivative having the general formula:
wherein A 1 , A 2 , A 3 , and A 4 may be the same or different and are selected from the group consisting of C 2 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, and any combination thereof, and,
wherein one of (R1 and R 3 ), or (R 2 and R 4 ) are the same or different and are hydrogen or a ligand, and the other of (R 1 and R 3 ), or (R 2 and R 4 ) are —(CH 2 ) n —C(O)—R′, wherein each R′ group is the same or different from the other R′ group and is either a hydroxyl group or a ligand; and wherein n=1-4.
2 . The composition of claim 1 , wherein A 1 , A 2 , A 3 , and A 4 are each (—CH 2 —CH 2 )— groups and having the following structure:
wherein (R 1 and R 3 ) are the same or different and are hydrogen or a ligand and (R 1 ′ and R 2 ′) are the same or different and are a ligand or a hydroxyl group, and wherein n=1-4, and said TA2S derivative is a DO2S derivative.
3 . The composition of claim 2 , having the following structure:
a) (R 1 and R 3 ) are hydrogen and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; or,
(b) (R 1 and R 3 ) are ligands and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; and, and said DO2S derivative is a DO2S derivative-1.
4 . The composition of claim 1 , wherein said ligand is selected from the group consisting of a proliferation targeting ligand, an angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, a drug-based ligand, a microbial agent, a glucose-mimicking agent, a hypoxia targeting agent, an extracellular matrix targeting ligand, and any combination thereof.
5 . The composition of claim 2 , wherein said DO2S derivative further comprises at least one linker, wherein said at least one linker forms a link to conjugate said DO2S derivative to said ligand.
6 . The composition of claim 5 , wherein said at least one linker is selected from the group consisting of ethylenediamine, amino propanol, diethylenetriamine, aspartic acid, polyaspartic acid, glutamic acid, polyglutamic acid, lysine, polyethylene glycols, and any combination thereof.
7 . The composition of claim 1 , wherein said ligand is selected from the group consisting of glucosamine, tetraacetate mannose, octreotide, Hedgehog ligands, EGFR targeting molecules, nucleotides, nucleosides, cholesterol, estradiol, nanoparticles, carbon nanotubes, and any combination thereof.
8 . The composition of claim 2 , wherein the ligand is an anti-cancer compound.
9 . The composition of claim 2 , wherein the ligand is a carbohydrate.
10 . The composition of claim 2 , wherein said DO2S derivative is chelated to a metal species.
11 . The composition of claim 10 , wherein said metal species is copper, cobalt, platinum, iron, arsenic, rhenium, or germanium.
12 . The composition of claim 10 , wherein said metal species is a radionuclide.
13 . The composition of claim 12 , wherein said radionuclide is 45 Ti, 59 Fe, 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 89 Sr, 90 Y, 94m Tc, 99m Tc, 111 In, 149 Pm, 153 Gd, 153 Sm, 166 Ho, 177 Lu, 186 Re, 188 Re, 211 At, 212 Bi or 225 Ac.
14 . The composition of claim 13 , wherein said radionuclide is 68 Ga or 177 Lu.
15 . The composition of claim 2 , wherein said ligand comprises a drug.
16 . A method for the treatment or diagnosis of a medical condition in a subject comprising:
administering to the subject a composition, comprising:
a TA2S derivative having the general formula:
wherein A 1 , A 2 , A 3 , and A 4 may be the same or different and are selected from the group consisting of C 2 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, and any combination thereof; and,
wherein one of (R 1 and R 3 ), or (R 2 and R 4 ) are the same or different and are hydrogen or a ligand, and the other of (R 1 and R 3 ), or (R 2 and R 4 ) are —(CH 2 ) n —C(O)—R′, wherein each R′ group is the same or different from the other R′ group and is either a hydroxyl group or a ligand; and wherein n=1-4.
17 . The method of claim 16 , wherein A 1 , A 2 , A 3 , and A 4 are each —(CH 2 —CH 2 )— groups and having the Miming structure:
wherein (R 1 and R 3 ) are the same or different and are hydrogen or a ligand and (R 1 ′ and R 2 ′) are the same or different and are a ligand or a hydroxyl group, and wherein n=1-4, and said TA2S derivative is a DO2S derivative.
18 . The method of claim 17 , wherein the composition has the following structure:
a) (R 1 and R 3 ) are hydrogen and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; or,
(b) R 1 and R 3 ) are ligands and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; and,
and said DO2S derivative is a DO2S derivative-1.
19 . The method of claim 17 , wherein the subject is a mammal
20 . The method of claim 19 , wherein the mammal is a human.
21 . (canceled)
22 . The method of claim 21 , wherein said metal species is a radionuclide.
23 . The method of claim 22 , wherein said radionuclide is 45 Ti, 59 Fe, 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 89 Sr, 90 Y, 94m Tc, 99m Tc, 111 In, 149 Pm, 153 Gd, 153 Sm, 166 Ho, 177 Lu, 186 Re, 188 Re, 211 At, 212 Bi or 225 Ac.
24 . The method of claim 23 , wherein said radionuclide is 68 Ga or 177 Lu.
25 . The method of claim 21 , wherein said metal species is selected from the group consisting of divalent ions of: an element of atomic number 21 to 29, 42, 44, and 57 to 83; and, trivalent ions of an element of atomic number 21 to 29, 42, 44, and 57 to 83.
26 . The method of claim 17 , further comprising administering radiation therapy or surgery.
27 . The method of claim 17 , wherein said medical condition oondibon im cancer and said ligand is an anti-cancer compound,
28 . The method of claim 27 , further comprising administration of a second anti-cancer compound.
29 . The method of claim 17 , wherein said ligand is selected from the group consisting of a proliferation targeting ligand, angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, a drug-based ligand, a microbial agent, a glucose-mimicking agent, a hypoxia targeting agent, an extracellular matrix targeting ligand, and. any combination thereof.
30 . The method of claim 17 , wherein said DO2S derivative further comprises at least one linker, wherein said at least one linker forms a link to conjugate said DO2S derivative to said ligand.
31 . The method of claim 30 , wherein said at least one linker is selected from the group consisting of ethylenediamine, amino propanol, diethylenetriamine, aspartic acid, polyaspartic acid, glutamic acid, polyglutamic acid, lysine, polyethylene glycols, and any combination thereof.
32 . The method of claim 17 , wherein said ligand is selected from the group consisting of glucosamine, tetraacetate mannose, octreotide, Hedgehog ligands, EGFR targeting molecules, nucleotides, nucleosides, cholesterol, estradiol, nanoparticles, carbon nanotubes, and any combination thereof.
33 . The method of claim 17 , wherein the ligand is an anti-cancer compound.
34 . The method of claim 17 , wherein the ligand is a carbohydrate.
35 . A kit for the treatment or diagnosis of a medical condition in a subject, said kit comprising:
a composition comprising:
a TA2S derivative conjugated to a therapeutic or diagnostic ligand and optionally chelated to a metal, wherein said TA2S derivative comprises the general formula:
wherein A 1 , A 2 , A 3 , and A 4 may be the same or different and are selected from the group consisting of C 2 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, and any combination thereof; and,
wherein one of (R 1 and R 3 ), or (R2 and R 4 .) are the same or different and are hydrogen or a ligand, and the other of (R 1 and R 3 ), or (R 2 and R 4 ) are —(CH 2 ) n —C(O)—R′, wherein each R′ group is the same or different from the other R′ group and is either a hydroxyl group or a ligand; and wherein n=1-4.
36 . The kit of claim 35 , wherein A 1 , A 2 , A 3 and A 4 are each —(CH 2 —CH 2 )— groups and having the following structure:
wherein (R 1 and R 3 ) are the same or different and are hydrogen or a ligand and (R 1 ′ and R 2 ′) are the same or different and are a ligand or a hydroxyl group, and wherein n=1-4, and said TITA2S derivative is a DO2S derivative.
37 . The kit of claim 36 , wherein the DO2S derivative has the following structure:
a) (R 1 and R 3 ) are hydrogen and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; or,
(b) (R 1 and R 3 ) are ligands and (R 1 ′ and R 2 ′) are the same or different and are a ligand or hydroxyl group; and,
and said DO2S derivative is a DO2S derivative-1.
38 . The kit of claim 36 , wherein said metal is a radionuclide.
39 . The kit of claim 38 , wherein the radionuclide is 45 Ti, 59 Fe, 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 89 Sr, 90 Y, 94m Tc, 99m Tc, 111 In, 149 Pm, 153 Gd, 153 Sm, 166 Ho, 177 Lu, 186 Re, 188 Re, 211 At, 212 Bi or 225 Ac.
40 . The kit of claim 39 , wherein the radionuclide is 68 Ga or 177 Lu.
41 . The kit of claim 36 , further comprising an antioxidant.
42 . The kit of claim 41 , wherein the antioxidant is vitamin C, tocopherol, pyridoxine, thiamine, or rutin.
43 . The kit of claim 36 , further comprising a transchelator.
44 . The kit of claim 43 wherein the transchelator is glucoheptonate, gluconate, glucarate, citrate, tartarate, DOTA, diethylenetriaminepentaacetic acid, or ethylenediaminetetraacetic acid.
45 . The kit of claim 36 , further comprising a reducing agent.
46 . The kit of claim 45 , wherein said reducing agent is tin (II) chloride or triphenylphosphine.
47 . The kit of claim 36 , wherein said ligand is a tumor targeting ligand.
48 . The kit of claim 36 , wherein said ligand is selected from the group consisting of a proliferation targeting ligand, an angiogenesis targeting ligand, a tumor apoptosis targeting ligand, a disease receptor targeting ligand, a drug-based ligand, a microbial agent, a glucose-mimicking agent, a hypoxia targeting agent, an extracellular matrix targeting ligand, and any combination thereof.
49 . The kit of claim 36 , wherein said DO2S derivative further comprises at least one linker, wherein said at least one linker forms a link to conjugate said DO2S derivative to said targeting ligand.
50 . The kit of claim 49 , wherein said at least one linker is selected from the group consisting of ethylenediamine, amino propanol, diethylenetriamine, aspartic acid, polyaspartic acid, glutamic acid, polyglutamic acid, lysine, polyethylene glycols, and any combination thereof.
51 . The kit of claim 36 , wherein said ligand is selected from the group consisting of glucosamine tetraacetate mannose, octreotide, Hedgehog ligands, EGFR targeting molecules, nucleotides, nucleosides, cholesterol, estradiol, nanoparticles, carbon nanotubes, and any combination thereof.
52 . The kit of claim 36 , wherein the ligand is an anti-cancer compound.
53 . The kit of claim 36 , wherein the ligand is a carbohydrate.
54 . The composition of claim 1 , further comprising a metal comprising a metallic chemotherapeutic agent or a radiotherapeutic agent chelated to the T A 2 S derivative.
55 . The composition of claim 2 , wherein the DO2S derivative comprises a phospholipid according to the following formula:
wherein Me is a metal.
56 . The composition of claim 2 , wherein the DO2S derivative comprises one of the following structures:
wherein L is a linker and Me is a metal.
57 . The method of claim 16 , further comprising imaging said subject.
58 . The method of claim 16 , wherein the TA2S derivative comprises a DO2S derivative, the method further comprising synthesizing the TA2S derivative by attaching a ligand to the DO2S derivative by replacing the hydrogen at the (R 1 and R 3 ) with the ligand.
59 . The method of claim 58 , wherein the synthesizing comprises:
60 . The method of claim 16 , wherein the TA2S derivative comprises a DO2S derivative and wherein the (R2 and R4) are —(CH2)n—C(O)—R′, the method further comprising synthesizing the TA2S derivative by attaching the ligand to the DO2S derivative by replacing the R′ with the ligand.
61 . The meth of claim 60 , wherein the synthesizing comprises:
62 . The method of claim 16 , wherein the TA2S derivative comprises a DO2S derivative, the method further comprising synthesizing the TA2S derivative by attaching a peptide to the DO2S derivative.
63 . The method of claim 62 , wherein the synthesizing comprises:
wherein Cbz are carbobenzyl groups, Bn are benzyl groups, and Me is a metal.Cited by (0)
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