Combination of para-aminohippuric acid (pah) and radiolabeled complexes for treating cancer
AssigneeITM Isotopen Technologien München AG
InventorsMarian MECKEL, Theresa OSL, Konstantin ZHERNOSEKOV
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Abstract
The present invention provides a combination comprising (a) a radiolabeled complex comprising a radionuclide and a targeting molecule linked to a chelating agent, and (b) para-aminohippuric acid (PAH) or a salt or derivate thereof for the treatment of cancer. Moreover, a pharmaceutical composition comprising (a) a radiolabeled complex comprising a radionuclide and a targeting molecule linked to a chelating agent, and (b) para-aminohippuric acid (PAH) or a salt or derivate thereof is provided for the treatment of cancer. The radiolabeled complex and PAH may be used in a combination therapy for the treatment of cancer.
Claims56
A combination of
- (a) a radiolabeled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent;
- and
- (b) para-aminohippuric acid (PAH), or a salt or carboxylic acid derivative thereof;
- for use in the treatment of cancer.
The combination for use according to any one of the previous claims, wherein the targeting molecule binds to PSMA or a somatostatin receptor (SSTR), in particular SSTR-2.
The combination for use according to any one of the previous claims, wherein the targeting molecule is selected from the group consisting of Tyr3-octeotride, Tyr3-octreotate, JR11, PSMA-11, Sargastrin, RGD and folate.
The combination for use according to any one of the previous claims, wherein the targeting molecule is octreotide, preferably Tyr3-octeotride.
The combination for use according to any one of the previous claims, wherein the chelating agent is a macrocyclic chelator, preferably selected from the group consisting of DOTA, HBED-CC, NOTA, NODAGA, DOTAGA, DOTAM, TRAP, NOPO, PCTA, DFO, DTPA, DO3AP, DO3APPrA, DO3APABn, and HYNIC or derivatives thereof.
The combination for use according to any one of the previous claims, wherein the chelating agent is DOTA.
The combination for use according to any one of the previous claims, wherein the radiolabeled complex comprises or consists of (i) the radionuclide and (ii) DOTATOC or DOTATATE.
The combination for use according to any one of the previous claims, wherein the radionuclide is selected from the group consisting of 94Tc, 99mTc, 90In, 111In, 67Ga, 68Ga, 86Y 90Y, 177Lu, 161Tb, 186Re, 188Re 64Cu, 67Cu, 55Co, 57Co, 43Sc, 44Sc, 47Sc, 225Ac, 213Bi, 212Bi, 212Pb, 227Th, 153Sm, 166Ho, 166Dy, 18F and 131I, preferably selected from the group consisting of 90In, 111In, 67Ga, 68Ga, 86Y, 90Y 177Lu, 161Tb, 64Cu, 67Cu, 55Co, 57Co, 43Sc, 44Sc, 47Sc, 225Ac, 213Bi, 212Bi, 212Pb, 153Sm, 166Ho, 225Ac and 166Dy.
The combination for use according to any one of the previous claims, wherein the radionuclide is selected from the group consisting of 177Lu, 68Ga 111In, 90Y, 99mTc, 223Ac and 161Tb, more preferably 177Lu, 223Ac and 68Ga, or selected from a tri-valent radionuclide, preferably selected from the group consisting of 177Lu, 90Y, 67Ga, 68Ga, 111In, 225Ac, 161Tb, 44Sc and 47Sc.
The combination for use according to any one of the previous claims, wherein the radionuclide is 177Lu (Lutetium-177).
The combination for use according to any one of the previous claims, wherein the radiolabeled complex is selected from [177Lu-DOTA∘-Tyr3]-octreotide, 177Lu-DOTA-JA11, 177Lu-DOTA-RGD, 177Lu-DOTA-Sargastrin, and 177Lu-PSMA I&T.
The combination for use according to any one of the previous claims, wherein the radiolabeled complex is 177Lu-DOTATOC.
The combination for use according to any one of the previous claims, wherein the combination comprises
- (a) the radiolabeled complex;
- and
- (b) para-aminohippuric acid (PAH).
The combination for use according to any one of the previous claims, wherein PAH or the salt or carboxylic acid derivate thereof is administered in a concentration of 5 mg to 500 mg per kilogram of body weight.
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered in a ratio from 1/240000 to 1/8000 (w/w).
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered on the same day.
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered at about the same time.
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered via the same route of administration.
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered systemically.
The combination for use according to any one of the previous claims, wherein (a) the radiolabeled complex and (b) PAH or the salt or carboxylic acid derivate thereof are administered in the same composition.
The combination for use according to any one of the previous claims, wherein the radiolabeled complex is administered once.
The combination for use according to any one of the previous claims, wherein the cancer is selected from neuroendocrine tumors, prostate cancer, pancreatic cancer, renal cancer, bladder cancer, medullar thyroid carcinomas, small cell lung cancers, stromal ovarian carcinomas, ductal pancreatic adenocarcinoma, insulinomas, gastrinomas, and breast cancer.
The combination for use according to any one of the previous claims, wherein the subject in need of the treatment is a human cancer patient.
A kit comprising
- (a) a radiolabeled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent;
- and
- (b) para-aminohippuric acid (PAH), or a salt or carboxylic acid derivative thereof;
- for use in the treatment of cancer.
A pharmaceutical composition comprising
- (a) a radiolabeled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent;
- and
- (b) para-aminohippuric acid (PAH), or a salt or carboxylic acid derivative thereof;
- for use in the treatment of cancer.
Para-aminohippuric acid (PAH), or the salt or carboxylic acid derivative thereof, for use in the treatment of cancer, wherein PAH, or the salt or carboxylic acid derivative thereof, is administered in combination with a radiolabelled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent.
A method for treating cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject
- (a) a radiolabeled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent;
- and
- (b) para-aminohippuric acid (PAH), or a salt or carboxylic acid derivative thereof.
A combination therapy for the treatment of cancer comprising combined administration of
- (a) a radiolabeled complex comprising (i) a radionuclide and (ii) a targeting molecule linked to a chelating agent;
- and
- (b) para-aminohippuric acid (PAH), or a salt or carboxylic acid derivative thereof.
Dependencies are inferred from the claim text.