TARGETING COMPOUNDS FOR CANCERS SELECTED FROM ESOPHAGUS, PHARYNX AND LARYNX, LUNG, BRAIN, AND INTESTINES

Abstract

Systems for use as a medicament for cancers selected from esophagus, pharynx and larynx, lung, brain, and intestines, include a targeting molecule for binding necrotic cells, a chelator, and a radionuclide, to a dosage comprising the system. In particular, the systems relate to compositions targeting necrotic cells.

Claims

1. A targeting system for use as a drug for cancers selected from esophagus, pharynx and larynx, lung, brain, and intestines, the system comprising a targeting molecule for binding to necrotic cells, the targeting molecule being a cyanine selected from HQ4, HQ5, CW-800 and ZW-800, and combinations thereof, ##STR00001## ##STR00002## wherein the cyanine is attached to a chelator, wherein the chelator is selected from DOTA and NOTA, and combinations thereof, ##STR00003## and attached to the chelator a radionuclide selected from Cu, In, Gd, Ga, Lu, Y, I, and Zr, and combinations thereof.

2. The targeting system according to claim 1 wherein the targeting molecule is neutral or negatively charged.

3. The targeting system according to claim 1, wherein the targeting molecule-chelator is selected from HQ4-DOTA, HQ5-DOTA, CW 800-DOTA, ZW800-DOTA, HQ4-NOTA, HQ5-NOTA, CW 800-NOTA, ZW800-NOTA, and combinations thereof.

4. The targeting system according to claim 1, wherein the radionuclide is selected from a group consisting of .sup.64Cu, .sup.67Cu, .sup.67Ga, .sup.68Ga, .sup.70Ga, .sup.72Ga, .sup.89Zr, .sup.90Y, .sup.95Z, .sup.111In, .sup.114In, .sup.123I, .sup.124I, .sup.153Gd, .sup.159Gd, and .sup.177Lu, and combinations thereof, wherein the radionuclide is present as a cation, with a valence of 0, 1, 2, 3, or 4, comprising at least one of Cu.sup.+, Cu.sup.2+, Cu.sup.3+, Cu.sup.4+, Ga.sup.+, Ga.sup.2+, Ga.sup.3+, Gd.sup.+, Gd.sup.2+, Gd.sup.3+, I.sup.+, I.sup.3+, In.sup.+, In.sup.2+, In.sup.3+, Lu.sup.3+, Zr, Zr.sup.2+, Zr.sup.3+, Zr.sup.4+, Y.sup.2+, and Y.sup.3+.

5. The targeting system according to claim 1, wherein the chelator-radionuclide is selected from .sup.64Cu.sub.y-DOTA, .sup.67Cu.sub.y-DOTA, .sup.67Ga.sub.y-DOTA, .sup.68Ga.sub.y-DOTA, .sup.70Ga.sub.y-DOTA, .sup.72Ga.sub.y-DOTA, .sup.89Zr.sub.y-DOTA, .sup.90Y.sub.y-DOTA, .sup.95Zr.sub.y-DOTA, .sup.111In.sub.y-DOTA, .sup.114In.sub.y-DOTA, .sup.123I.sub.y-DOTA, .sup.124I.sub.y-DOTA, .sup.153Gd.sub.y-DOTA, .sup.159Gd.sub.y-DOTA, .sup.177Lu.sub.y-DOTA, .sup.64Cu.sub.y-NOTA, .sup.67Cu.sub.y-NOTA, .sup.67Ga.sub.y-NOTA, .sup.68Ga.sub.y-NOTA, .sup.70Ga.sub.y-NOTA, .sup.72Ga.sub.y-NOTA, .sup.89Zr.sub.y-NOTA, .sup.90Y.sub.y-NOTA, .sup.95Zr.sub.y-NOTA, .sup.111In.sub.y-NOTA, .sup.114In.sub.y-NOTA, .sup.123I.sub.y-NOTA, .sup.124I.sub.y-NOTA, .sup.153Gd.sub.y-NOTA, .sup.159Gd.sub.y-NOTA, .sup.177Lu.sub.y-NOTA, and combinations thereof, wherein y∈[1,2,3,4].

6. The targeting system according to claim 1, wherein the combination of cyanine and radionuclide is selected from .sup.64Cu/HQ4, .sup.67Cu/HQ4, .sup.67Ga/HQ4, .sup.68Ga/HQ4, .sup.70Ga/HQ4, .sup.72Ga/HQ4, .sup.89Zr/HQ4, .sup.90Y/HQ4, .sup.95Zr/HQ4, .sup.111In/HQ4, .sup.114In/HQ4, .sup.123/HQ4, .sup.124I/HQ4, .sup.153Gd/HQ4, .sup.159Gd/HQ4, .sup.177Lu/HQ4, .sup.64Cu/HQ5, .sup.67Cu/HQ5, .sup.67Ga/HQ5, .sup.68Ga/HQ5, .sup.70Ga/HQ5, .sup.72Ga/HQ5, .sup.89Zr/HQ5, .sup.90Y/HQ5, .sup.95Zr/HQ5, .sup.111In/HQ5, .sup.114In/HQ5, .sup.123I/HQ5, .sup.124I/HQ5, .sup.153Gd/HQ5, .sup.159Gd/HQ5, .sup.177Lu/HQ5, .sup.64Cu/CW800, .sup.67Cu/CW800, .sup.67Ga/CW800, .sup.68Ga/CW800, .sup.70Ga/CW800, .sup.72Ga/CW800, .sup.89Zr/CW800, .sup.90Y/CW800, .sup.95Zr/CW800, .sup.111In/CW800, .sup.114In/CW800, .sup.123I/CW800, .sup.124I/CW800, .sup.153Gd/CW800, .sup.159Gd/CW800, .sup.177Lu/CW800, .sup.64Cu/ZW800, .sup.67Cu/ZW800, .sup.67Ga/ZW800, .sup.68Ga/ZW800, .sup.70Ga/ZW800, .sup.72Ga/ZW800, .sup.89Zr/ZW800, .sup.90Y/ZW800, .sup.95Zr/ZW800, .sup.111In/ZW800, .sup.114In/ZW800, .sup.123I/ZW800, .sup.124I/ZW800, .sup.153Gd/ZW800, .sup.159Gd/ZW800, .sup.177Lu/ZW800, and combinations thereof.

7. A targeting system drug for esophagus cancer selected from .sup.64Cu.sub.y-DOTA-HQ4, .sup.67Cu.sub.y-DOTA-HQ4, .sup.67Ga.sub.y-DOTA-HQ4, .sup.68Ga.sub.y-DOTA-HQ4, .sup.70Ga.sub.y-DOTA-HQ4, .sup.72Ga.sub.y-DOTA-HQ4, .sup.89Zr.sub.y-DOTA-HQ4, .sup.90Y.sub.y-DOTA-HQ4, .sup.95Zr.sub.y-DOTA-HQ4, .sup.111In.sub.y-DOTA-HQ4, .sup.114In.sub.y-DOTA-HQ4, .sup.123I.sub.y-DOTA-HQ4, .sup.124I.sub.y-DOTA-HQ4, .sup.153Gd.sub.y-DOTA-HQ4, .sup.159Gd.sub.y-DOTA-HQ4, .sup.177Lu.sub.y-DOTA-HQ4, .sup.64Cu.sub.y-DOTA-HQ5, .sup.67Cu.sub.y-DOTA-HQ5, .sup.67Ga.sub.y-DOTA-HQ5, .sup.68Ga.sub.y-DOTA-HQ5, .sup.70Ga.sub.y-DOTA-HQ5, .sup.72Ga.sub.y-DOTA-HQ5, .sup.89Zr.sub.y-DOTA-HQ5, .sup.90Y.sub.y-DOTA-HQ5, .sup.95Zr.sub.y-DOTA-HQ5, .sup.111In.sub.y-DOTA-HQ5, .sup.114In.sub.y-DOTA-HQ5, .sup.123I.sub.y-DOTA-HQ5, .sup.124I.sub.y-DOTA-HQ5, .sup.153Gd.sub.y-DOTA-HQ5, .sup.159Gd.sub.y-DOTA-HQ5, .sup.177Lu.sub.y-DOTA-HQ5, .sup.64Cu.sub.y-DOTA-CW800, .sup.67Cu.sub.y-DOTA-CW800, .sup.67Ga.sub.y-DOTA-CW800, .sup.68Ga.sub.y-DOTA-CW800, .sup.70Ga.sub.y-DOTA-CW800, .sup.72Ga.sub.y-DOTA-CW800, .sup.89Zr.sub.y-DOTA-CW800, .sup.90Y.sub.y-DOTA-CW800, .sup.95Zr.sub.y-DOTA-CW800, .sup.11In.sub.y-DOTA-CW800, .sup.114In.sub.y-DOTA-CW800, .sup.123I.sub.y-DOTA-CW800, .sup.124I.sub.y-DOTA-CW800, .sup.153Gd.sub.y-DOTA-CW800, .sup.159Gd.sub.y-DOTA-CW800, .sup.177Lu.sub.y-DOTA-CW800, .sup.64Cu.sub.y-DOTA-ZW800, .sup.67Cu.sub.y-DOTA-ZW800, .sup.67Ga.sub.y-DOTA-ZW800, .sup.68Ga.sub.y-DOTA-ZW800, .sup.70Ga.sub.y-DOTA-ZW800, .sup.72Ga.sub.y-DOTA-ZW800, .sup.89Zr.sub.y-DOTA-ZW800, .sup.90Y.sub.y-DOTA-ZW800, .sup.95Zr.sub.y-DOTA-ZW800, .sup.111In.sub.y-DOTA-ZW800, .sup.114In.sub.y-DOTA-ZW800, .sup.123I.sub.y-DOTA-ZW800, .sup.124I.sub.y-DOTA-ZW800, .sup.153Gd.sub.y-DOTA-ZW800, .sup.159Gd.sub.y-DOTA-ZW800, .sup.177Lu.sub.y-DOTA-ZW800, .sup.64Cu.sub.y-NOTA-HQ4, .sup.67Cu.sub.y-NOTA-HQ4, .sup.67Ga.sub.y-NOTA-HQ4, .sup.68Ga.sub.y-NOTA-HQ4, .sup.70Ga.sub.y-NOTA-HQ4, .sup.72Ga.sub.y-NOTA-HQ4, .sup.89Zr.sub.y-NOTA-HQ4, .sup.90Y.sub.y-NOTA-HQ4, .sup.95Zr.sub.y-NOTA-HQ4, .sup.111In.sub.y-NOTA-HQ4, .sup.114In.sub.y-NOTA-HQ4, .sup.123I.sub.y-NOTA-HQ4, .sup.124I.sub.y-NOTA-HQ4, .sup.153Gd.sub.y-NOTA-HQ4, .sup.159Gd.sub.y-NOTA-HQ4, .sup.177Lu.sub.y-NOTA-HQ4, .sup.64Cu.sub.y-NOTA-HQ5, .sup.67Cu.sub.y-NOTA-HQ5, .sup.67Ga.sub.y-NOTA-HQ5, .sup.68Ga.sub.y-NOTA-HQ5, .sup.70Ga.sub.y-NOTA-HQ5, .sup.72Ga.sub.y-NOTA-HQ5, .sup.89Zr.sub.y-NOTA-HQ5, .sup.90Y.sub.y-NOTA-HQ5, .sup.95Zr.sub.y-NOTA-HQ5, .sup.111In.sub.y-NOTA-HQ5, .sup.114In.sub.y-NOTA-HQ5, .sup.123I.sub.y-NOTA-HQ5, .sup.124I.sub.y-NOTA-HQ5, .sup.153Gd.sub.y-NOTA-HQ5, .sup.159Gd.sub.y-NOTA-HQ5, .sup.177Lu.sub.y-NOTA-HQ5, .sup.64Cu.sub.y-NOTA-CW800, .sup.67Cu.sub.y-NOTA-CW800, .sup.67Ga.sub.y-NOTA-CW800, .sup.68Ga.sub.y-NOTA-CW800, .sup.70Ga.sub.y-NOTA-CW800, .sup.72Ga.sub.y-NOTA-CW800, .sup.89Zr.sub.y-NOTA-CW800, .sup.90Y.sub.y-NOTA-CW800, .sup.95Zr.sub.y-NOTA-CW800, .sup.111In.sub.y-NOTA-CW800, .sup.114In.sub.y-NOTA-CW800, .sup.123I.sub.y-NOTA-CW800, .sup.124I.sub.y-NOTA-CW800, .sup.153Gd.sub.y-NOTA-CW800, .sup.159Gd.sub.y-NOTA-CW800, .sup.177Lu.sub.y-NOTA-CW800, .sup.64Cu.sub.y-NOTA-ZW800, .sup.67Cu.sub.y-NOTA-ZW800, .sup.67Ga.sub.y-NOTA-ZW800, .sup.68Ga.sub.y-NOTA-ZW800, .sup.70Ga.sub.y-NOTA-ZW800, .sup.72Ga.sub.y-NOTA-ZW800, .sup.89Zr.sub.y-NOTA-ZW800, .sup.90Y.sub.y-NOTA-ZW800, .sup.95Zr.sub.y-NOTA-ZW800, .sup.111In.sub.y-NOTA-ZW800, .sup.114In.sub.y-NOTA-ZW800, .sup.123I.sub.y-NOTA-ZW800, .sup.124I.sub.y-NOTA-ZW800, .sup.153Gd.sub.y-NOTA-ZW800, .sup.159Gd.sub.y-NOTA-ZW800, .sup.177Lu.sub.y-NOTA-ZW800, and combinations thereof, wherein ye[1,2,3,4].

8. A targeting system drug for lung cancer selected from .sup.64Cu.sub.y-DOTA-HQ4, .sup.67Cu.sub.y-DOTA-HQ4, .sup.67Ga.sub.y-DOTA-HQ4, .sup.68Ga.sub.y-DOTA-HQ4, .sup.70Ga.sub.y-DOTA-HQ4, .sup.72Ga.sub.y-DOTA-HQ4, .sup.89Zr.sub.y-DOTA-HQ4, .sup.90Y.sub.y-DOTA-HQ4, .sup.95Zr.sub.y-DOTA-HQ4, .sup.111In.sub.y-DOTA-HQ4, .sup.114In.sub.y-DOTA-HQ4, .sup.123I.sub.y-DOTA-HQ4, .sup.124I.sub.y-DOTA-HQ4, .sup.153Gd.sub.y-DOTA-HQ4, .sup.159Gd.sub.y-DOTA-HQ4, .sup.177Lu.sub.y-DOTA-HQ4, .sup.64Cu.sub.y-DOTA-HQ5, .sup.67Cu.sub.y-DOTA-HQ5, .sup.67Ga.sub.y-DOTA-HQ5, .sup.68Ga.sub.y-DOTA-HQ5, .sup.70Ga.sub.y-DOTA-HQ5, .sup.72Ga.sub.y-DOTA-HQ5, .sup.89Zr.sub.y-DOTA-HQ5, .sup.90Y.sub.y-DOTA-HQ5, .sup.95Zr.sub.y-DOTA-HQ5, .sup.111In.sub.y-DOTA-HQ5, .sup.114In.sub.y-DOTA-HQ5, .sup.123I.sub.y-DOTA-HQ5, .sup.124I.sub.y-DOTA-HQ5, .sup.153Gd.sub.y-DOTA-HQ5, .sup.159Gd.sub.y-DOTA-HQ5, .sup.177Lu.sub.y-DOTA-HQ5, .sup.64Cu.sub.y-DOTA-CW800, .sup.67Cu.sub.y-DOTA-CW800, .sup.67Ga.sub.y-DOTA-CW800, .sup.68Ga.sub.y-DOTA-CW800, .sup.70Ga.sub.y-DOTA-CW800, .sup.72Ga.sub.y-DOTA-CW800, .sup.89Zr.sub.y-DOTA-CW800, .sup.90Y.sub.y-DOTA-CW800, .sup.95Zr.sub.y-DOTA-CW800, .sup.111In.sub.y-DOTA-CW800, .sup.114In.sub.y-DOTA-CW800, .sup.123I.sub.y-DOTA-CW800, .sup.124I.sub.y-DOTA-CW800, .sup.153Gd.sub.y-DOTA-CW800, .sup.159Gd.sub.y-DOTA-CW800, .sup.177Lu.sub.y-DOTA-CW800, .sup.64Cu.sub.y-DOTA-ZW800, .sup.67Cu.sub.y-DOTA-ZW800, .sup.67Ga.sub.y-DOTA-ZW800, .sup.68Ga.sub.y-DOTA-ZW800, .sup.70Ga.sub.y-DOTA-ZW800, .sup.72Ga.sub.y-DOTA-ZW800, .sup.89Zr.sub.y-DOTA-ZW800, .sup.90Y.sub.y-DOTA-ZW800, .sup.95Zr.sub.y-DOTA-ZW800, .sup.111In.sub.y-DOTA-ZW800, .sup.114In.sub.y-DOTA-ZW800, .sup.123I.sub.y-DOTA-ZW800, .sup.124I.sub.y-DOTA-ZW800, .sup.153Gd.sub.y-DOTA-ZW800, .sup.159Gd.sub.y-DOTA-ZW800, .sup.177Lu.sub.y-DOTA-ZW800, .sup.64Cu.sub.y-NOTA-HQ4, .sup.67Cu.sub.y-NOTA-HQ4, .sup.67Ga.sub.y-NOTA-HQ4, .sup.68Ga.sub.y-NOTA-HQ4, .sup.70Ga.sub.y-NOTA-HQ4, .sup.72Ga.sub.y-NOTA-HQ4, .sup.89Zr.sub.y-NOTA-HQ4, .sup.90Y.sub.y-NOTA-HQ4, .sup.95Zr.sub.y-NOTA-HQ4, .sup.111In.sub.y-NOTA-HQ4, .sup.114In.sub.y-NOTA-HQ4, .sup.123I.sub.y-NOTA-HQ4, .sup.124I.sub.y-NOTA-HQ4, .sup.153Gd.sub.y-NOTA-HQ4, .sup.159Gd.sub.y-NOTA-HQ4, .sup.177Lu.sub.y-NOTA-HQ4, .sup.64Cu.sub.y-NOTA-HQ5, .sup.67Cu.sub.y-NOTA-HQ5, .sup.67Ga.sub.y-NOTA-HQ5, .sup.68Ga.sub.y-NOTA-HQ5, .sup.70Ga.sub.y-NOTA-HQ5, .sup.72Ga.sub.y-NOTA-HQ5, .sup.89Zr.sub.y-NOTA-HQ5, .sup.90Y.sub.y-NOTA-HQ5, .sup.95Zr.sub.y-NOTA-HQ5, .sup.111In.sub.y-NOTA-HQ5, .sup.114In.sub.y-NOTA-HQ5, .sup.123I.sub.y-NOTA-HQ5, .sup.124I.sub.y-NOTA-HQ5, .sup.153Gd.sub.y-NOTA-HQ5, .sup.159Gd.sub.y-NOTA-HQ5, .sup.177Lu.sub.y-NOTA-HQ5, .sup.64Cu.sub.y-NOTA-CW800, .sup.67Cu.sub.y-NOTA-CW800, .sup.67Ga.sub.y-NOTA-CW800, .sup.68Ga.sub.y-NOTA-CW800, .sup.70Ga.sub.y-NOTA-CW800, .sup.72Ga.sub.y-NOTA-CW800, .sup.89Zr.sub.y-NOTA-CW800, .sup.90Y.sub.y-NOTA-CW800, .sup.95Zr.sub.y-NOTA-CW800, .sup.111In.sub.y-NOTA-CW800, .sup.114In.sub.y-NOTA-CW800, .sup.123I.sub.y-NOTA-CW800, .sup.124I.sub.y-NOTA-CW800, .sup.153Gd.sub.y-NOTA-CW800, .sup.159Gd.sub.y-NOTA-CW800, .sup.177Lu.sub.y-NOTA-CW800, .sup.64Cu.sub.y-NOTA-ZW800, .sup.67Cu.sub.y-NOTA-ZW800, .sup.67Ga.sub.y-NOTA-ZW800, .sup.68Ga.sub.y-NOTA-ZW800, .sup.70Ga.sub.y-NOTA-ZW800, .sup.72Ga.sub.y-NOTA-ZW800, .sup.89Zr.sub.y-NOTA-ZW800, .sup.90Y.sub.y-NOTA-ZW800, .sup.95Zr.sub.y-NOTA-ZW800, .sup.111In.sub.y-NOTA-ZW800, .sup.114In.sub.y-NOTA-ZW800, .sup.123I.sub.y-NOTA-ZW800, .sup.124I.sub.y-NOTA-ZW800, .sup.153Gd.sub.y-NOTA-ZW800, .sup.159Gd.sub.y-NOTA-ZW800, .sup.177Lu.sub.y-NOTA-ZW800, and combinations thereof, wherein y∈[1,2,3,4].

9. A targeting system drug for intestine cancer selected from .sup.64Cu.sub.y-DOTA-HQ4, .sup.67Cu.sub.y-DOTA-HQ4, .sup.67Ga.sub.y-DOTA-HQ4, .sup.68Ga.sub.y-DOTA-HQ4, .sup.70Ga.sub.y-DOTA-HQ4, .sup.72Ga.sub.y-DOTA-HQ4, .sup.89Zr.sub.y-DOTA-HQ4, .sup.90Y.sub.y-DOTA-HQ4, .sup.95Zr.sub.y-DOTA-HQ4, .sup.111In.sub.y-DOTA-HQ4, .sup.114In.sub.y-DOTA-HQ4, .sup.123I.sub.y-DOTA-HQ4, .sup.124I.sub.y-DOTA-HQ4, .sup.153Gd.sub.y-DOTA-HQ4, .sup.159Gd.sub.y-DOTA-HQ4, .sup.177Lu.sub.y-DOTA-HQ4, .sup.64Cu.sub.y-DOTA-HQ5, .sup.67Cu.sub.y-DOTA-HQ5, .sup.67Ga.sub.y-DOTA-HQ5, .sup.68Ga.sub.y-DOTA-HQ5, .sup.70Ga.sub.y-DOTA-HQ5, .sup.72Ga.sub.y-DOTA-HQ5, .sup.89Zr.sub.y-DOTA-HQ5, .sup.90Y.sub.y-DOTA-HQ5, .sup.95Zr.sub.y-DOTA-HQ5, .sup.111In.sub.y-DOTA-HQ5, .sup.114In.sub.y-DOTA-HQ5, .sup.123I.sub.y-DOTA-HQ5, .sup.124I.sub.y-DOTA-HQ5, .sup.153Gd.sub.y-DOTA-HQ5, .sup.159Gd.sub.y-DOTA-HQ5, .sup.177Lu.sub.y-DOTA-HQ5, .sup.64Cu.sub.y-DOTA-CW800, .sup.67Cu.sub.y-DOTA-CW800, .sup.67Ga.sub.y-DOTA-CW800, .sup.68Ga.sub.y-DOTA-CW800, .sup.70Ga.sub.y-DOTA-CW800, .sup.72Ga.sub.y-DOTA-CW800, .sup.89Zr.sub.y-DOTA-CW800, .sup.90Y.sub.y-DOTA-CW800, .sup.95Zr.sub.y-DOTA-CW800, .sup.111In.sub.y-DOTA-CW800, .sup.114In.sub.y-DOTA-CW800, .sup.123I.sub.y-DOTA-CW800, .sup.124I.sub.y-DOTA-CW800, .sup.153Gd.sub.y-DOTA-CW800, .sup.159Gd.sub.y-DOTA-CW800, .sup.177Lu.sub.y-DOTA-CW800, .sup.64Cu.sub.y-DOTA-ZW800, .sup.67Cu.sub.y-DOTA-ZW800, .sup.67Ga.sub.y-DOTA-ZW800, .sup.68Ga.sub.y-DOTA-ZW800, .sup.70Ga.sub.y-DOTA-ZW800, .sup.72Ga.sub.y-DOTA-ZW800, .sup.89Zr.sub.y-DOTA-ZW800, .sup.90Y.sub.y-DOTA-ZW800, .sup.95Zr.sub.y-DOTA-ZW800, .sup.111In.sub.y-DOTA-ZW800, .sup.114In.sub.y-DOTA-ZW800, .sup.123I.sub.y-DOTA-ZW800, .sup.124I.sub.y-DOTA-ZW800, .sup.153Gd.sub.y-DOTA-ZW800, .sup.159Gd.sub.y-DOTA-ZW800, .sup.177Lu.sub.y-DOTA-ZW800, .sup.64Cu.sub.y-NOTA-HQ4, .sup.67Cu.sub.y-NOTA-HQ4, .sup.67Ga.sub.y-NOTA-HQ4, .sup.68Ga.sub.y-NOTA-HQ4, .sup.70Ga.sub.y-NOTA-HQ4, .sup.72Ga.sub.y-NOTA-HQ4, .sup.89Zr.sub.y-NOTA-HQ4, .sup.90Y.sub.y-NOTA-HQ4, .sup.95Zr.sub.y-NOTA-HQ4, .sup.111In.sub.y-NOTA-HQ4, .sup.114In.sub.y-NOTA-HQ4, .sup.123I.sub.y-NOTA-HQ4, .sup.124I.sub.y-NOTA-HQ4, .sup.153Gd.sub.y-NOTA-HQ4, .sup.159Gd.sub.y-NOTA-HQ4, .sup.177Lu.sub.y-NOTA-HQ4, .sup.64Cu.sub.y-NOTA-HQ5, .sup.67Cu.sub.y-NOTA-HQ5, .sup.67Ga.sub.y-NOTA-HQ5, .sup.68Ga.sub.y-NOTA-HQ5, .sup.70Ga.sub.y-NOTA-HQ5, .sup.72Ga.sub.y-NOTA-HQ5, .sup.89Zr.sub.y-NOTA-HQ5, .sup.90Y.sub.y-NOTA-HQ5, .sup.95Zr.sub.y-NOTA-HQ5, .sup.111In.sub.y-NOTA-HQ5, .sup.114In.sub.y-NOTA-HQ5, .sup.123I.sub.y-NOTA-HQ5, .sup.124I.sub.y-NOTA-HQ5, .sup.153Gd.sub.y-NOTA-HQ5, .sup.159Gd.sub.y-NOTA-HQ5, .sup.177Lu.sub.y-NOTA-HQ5, .sup.64Cu.sub.y-NOTA-CW800, .sup.67Cu.sub.y-NOTA-CW800, .sup.67Ga.sub.y-NOTA-CW800, .sup.68Ga.sub.y-NOTA-CW800, .sup.70Ga.sub.y-NOTA-CW800, .sup.72Ga.sub.y-NOTA-CW800, .sup.89Zr.sub.y-NOTA-CW800, .sup.90Y.sub.y-NOTA-CW800, .sup.95Zr.sub.y-NOTA-CW800, .sup.111In.sub.y-NOTA-CW800, .sup.114In.sub.y-NOTA-CW800, .sup.123I.sub.y-NOTA-CW800, .sup.124I.sub.y-NOTA-CW800, .sup.153Gd.sub.y-NOTA-CW800, .sup.159Gd.sub.y-NOTA-CW800, .sup.177Lu.sub.y-NOTA-CW800, .sup.64Cu.sub.y-NOTA-ZW800, .sup.67Cu.sub.y-NOTA-ZW800, .sup.67Ga.sub.y-NOTA-ZW800, .sup.68Ga.sub.y-NOTA-ZW800, .sup.70Ga.sub.y-NOTA-ZW800, .sup.72Ga.sub.y-NOTA-ZW800, .sup.89Zr.sub.y-NOTA-ZW800, .sup.90Y.sub.y-NOTA-ZW800, .sup.95Zr.sub.y-NOTA-ZW800, .sup.111In.sub.y-NOTA-ZW800, .sup.114In.sub.y-NOTA-ZW800, .sup.123I.sub.y-NOTA-ZW800, .sup.124I.sub.y-NOTA-ZW800, .sup.153Gd.sub.y-NOTA-ZW800, .sup.159Gd.sub.y-NOTA-ZW800, .sup.177Lu.sub.y-NOTA-ZW800, and combinations thereof, wherein y∈[1,2,3,4].

10. A targeting system drug for brain cancer selected from .sup.64Cu.sub.y-DOTA-HQ4, .sup.67Cu.sub.y-DOTA-HQ4, .sup.67Ga.sub.y-DOTA-HQ4, .sup.68Ga.sub.y-DOTA-HQ4, .sup.70Ga.sub.y-DOTA-HQ4, .sup.72Ga.sub.y-DOTA-HQ4, .sup.89Zr.sub.y-DOTA-HQ4, .sup.90Y.sub.y-DOTA-HQ4, .sup.95Zr.sub.y-DOTA-HQ4, .sup.111In.sub.y-DOTA-HQ4, .sup.114In.sub.y-DOTA-HQ4, .sup.123I.sub.y-DOTA-HQ4, .sup.124I.sub.y-DOTA-HQ4, .sup.153Gd.sub.y-DOTA-HQ4, .sup.159Gd.sub.y-DOTA-HQ4, .sup.177Lu.sub.y-DOTA-HQ4, .sup.64Cu.sub.y-DOTA-HQ5, .sup.67Cu.sub.y-DOTA-HQ5, .sup.67Ga.sub.y-DOTA-HQ5, .sup.68Ga.sub.y-DOTA-HQ5, .sup.70Ga.sub.y-DOTA-HQ5, .sup.72Ga.sub.y-DOTA-HQ5, .sup.89Zr.sub.y-DOTA-HQ5, .sup.90Y.sub.y-DOTA-HQ5, .sup.95Zr.sub.y-DOTA-HQ5, .sup.111In.sub.y-DOTA-HQ5, .sup.114In.sub.y-DOTA-HQ5, .sup.123I.sub.y-DOTA-HQ5, .sup.124I.sub.y-DOTA-HQ5, .sup.153Gd.sub.y-DOTA-HQ5, .sup.159Gd.sub.y-DOTA-HQ5, .sup.177Lu.sub.y-DOTA-HQ5, .sup.64Cu.sub.y-DOTA-CW800, .sup.67Cu.sub.y-DOTA-CW800, .sup.67Ga.sub.y-DOTA-CW800, .sup.68Ga.sub.y-DOTA-CW800, .sup.70Ga.sub.y-DOTA-CW800, .sup.72Ga.sub.y-DOTA-CW800, .sup.89Zr.sub.y-DOTA-CW800, .sup.90Y.sub.y-DOTA-CW800, .sup.95Zr.sub.y-DOTA-CW800, .sup.111In.sub.y-DOTA-CW800, .sup.114In.sub.y-DOTA-CW800, .sup.123I.sub.y-DOTA-CW800, .sup.124I.sub.y-DOTA-CW800, .sup.153Gd.sub.y-DOTA-CW800, .sup.159Gd.sub.y-DOTA-CW800, .sup.177Lu.sub.y-DOTA-CW800, .sup.64Cu.sub.y-DOTA-ZW800, .sup.67Cu.sub.y-DOTA-ZW800, .sup.67Ga.sub.y-DOTA-ZW800, .sup.68Ga.sub.y-DOTA-ZW800, .sup.70Ga.sub.y-DOTA-ZW800, .sup.72Ga.sub.y-DOTA-ZW800, .sup.89Zr.sub.y-DOTA-ZW800, .sup.90Y.sub.y-DOTA-ZW800, .sup.95Zr.sub.y-DOTA-ZW800, .sup.111In.sub.y-DOTA-ZW800, .sup.114In.sub.y-DOTA-ZW800, .sup.123I.sub.y-DOTA-ZW800, .sup.124I.sub.y-DOTA-ZW800, .sup.153Gd.sub.y-DOTA-ZW800, .sup.159Gd.sub.y-DOTA-ZW800, .sup.177Lu.sub.y-DOTA-ZW800, .sup.64Cu.sub.y-NOTA-HQ4, .sup.67Cu.sub.y-NOTA-HQ4, .sup.67Ga.sub.y-NOTA-HQ4, .sup.68Ga.sub.y-NOTA-HQ4, .sup.70Ga.sub.y-NOTA-HQ4, .sup.72Ga.sub.y-NOTA-HQ4, .sup.89Zr.sub.y-NOTA-HQ4, .sup.90Y.sub.y-NOTA-HQ4, .sup.95Zr.sub.y-NOTA-HQ4, .sup.111In.sub.y-NOTA-HQ4, .sup.114In.sub.y-NOTA-HQ4, .sup.123I.sub.y-NOTA-HQ4, .sup.124I.sub.y-NOTA-HQ4, .sup.153Gd.sub.y-NOTA-HQ4, .sup.159Gd.sub.y-NOTA-HQ4, .sup.177Lu.sub.y-NOTA-HQ4, .sup.64Cu.sub.y-NOTA-HQ5, .sup.67Cu.sub.y-NOTA-HQ5, .sup.67Ga.sub.y-NOTA-HQ5, .sup.68Ga.sub.y-NOTA-HQ5, .sup.70Ga.sub.y-NOTA-HQ5, .sup.72Ga.sub.y-NOTA-HQ5, .sup.89Zr.sub.y-NOTA-HQ5, .sup.90Y.sub.y-NOTA-HQ5, .sup.95Zr.sub.y-NOTA-HQ5, .sup.111In.sub.y-NOTA-HQ5, .sup.114In.sub.y-NOTA-HQ5, .sup.123I.sub.y-NOTA-HQ5, .sup.124I.sub.y-NOTA-HQ5, .sup.153Gd.sub.y-NOTA-HQ5, .sup.159Gd.sub.y-NOTA-HQ5, .sup.177Lu.sub.y-NOTA-HQ5, .sup.64Cu.sub.y-NOTA-CW800, .sup.67Cu.sub.y-NOTA-CW800, .sup.67Ga.sub.y-NOTA-CW800, .sup.68Ga.sub.y-NOTA-CW800, .sup.70Ga.sub.y-NOTA-CW800, .sup.72Ga.sub.y-NOTA-CW800, .sup.89Zr.sub.y-NOTA-CW800, .sup.90Y.sub.y-NOTA-CW800, .sup.95Zr.sub.y-NOTA-CW800, .sup.111In.sub.y-NOTA-CW800, .sup.114In.sub.y-NOTA-CW800, .sup.123I.sub.y-NOTA-CW800, .sup.124I.sub.y-NOTA-CW800, .sup.153Gd.sub.y-NOTA-CW800, .sup.159Gd.sub.y-NOTA-CW800, .sup.177Lu.sub.y-NOTA-CW800, .sup.64Cu.sub.y-NOTA-ZW800, .sup.67Cu.sub.y-NOTA-ZW800, .sup.67Ga.sub.y-NOTA-ZW800, .sup.68Ga.sub.y-NOTA-ZW800, .sup.70Ga.sub.y-NOTA-ZW800, .sup.72Ga.sub.y-NOTA-ZW800, .sup.89Zr.sub.y-NOTA-ZW800, .sup.90Y.sub.y-NOTA-ZW800, .sup.95Zr.sub.y-NOTA-ZW800, .sup.111In.sub.y-NOTA-ZW800, .sup.114In.sub.y-NOTA-ZW800, .sup.123I.sub.y-NOTA-ZW800, .sup.124I.sub.y-NOTA-ZW800, .sup.153Gd.sub.y-NOTA-ZW800, .sup.159Gd.sub.y-NOTA-ZW800, .sup.177Lu.sub.y-NOTA-ZW800, and combinations thereof, wherein y∈[1,2,3,4].

11. A targeting system drug for pharynx cancer or for larynx cancer selected from .sup.64Cu.sub.y-DOTA-HQ4, .sup.67Cu.sub.y-DOTA-HQ4, .sup.67Ga.sub.y-DOTA-HQ4, .sup.68Ga.sub.y-DOTA-HQ4, .sup.70Ga.sub.y-DOTA-HQ4, .sup.72Ga.sub.y-DOTA-HQ4, .sup.89Zr.sub.y-DOTA-HQ4, .sup.90Y.sub.y-DOTA-HQ4, .sup.95Zr.sub.y-DOTA-HQ4, .sup.111In.sub.y-DOTA-HQ4, .sup.114In.sub.y-DOTA-HQ4, .sup.123I.sub.y-DOTA-HQ4, .sup.124I.sub.y-DOTA-HQ4, .sup.153Gd.sub.y-DOTA-HQ4, .sup.159Gd.sub.y-DOTA-HQ4, .sup.177Lu.sub.y-DOTA-HQ4, .sup.64Cu.sub.y-DOTA-HQ5, .sup.67Cu.sub.y-DOTA-HQ5, .sup.67Ga.sub.y-DOTA-HQ5, .sup.68Ga.sub.y-DOTA-HQ5, .sup.70Ga.sub.y-DOTA-HQ5, .sup.72Ga.sub.y-DOTA-HQ5, .sup.89Zr.sub.y-DOTA-HQ5, .sup.90Y.sub.y-DOTA-HQ5, .sup.95Zr.sub.y-DOTA-HQ5, .sup.111In.sub.y-DOTA-HQ5, .sup.114In.sub.y-DOTA-HQ5, .sup.123I.sub.y-DOTA-HQ5, .sup.124I.sub.y-DOTA-HQ5, .sup.153Gd.sub.y-DOTA-HQ5, .sup.159Gd.sub.y-DOTA-HQ5, .sup.177Lu.sub.y-DOTA-HQ5, .sup.64Cu.sub.y-DOTA-CW800, .sup.67Cu.sub.y-DOTA-CW800, .sup.67Ga.sub.y-DOTA-CW800, .sup.68Ga.sub.y-DOTA-CW800, .sup.70Ga.sub.y-DOTA-CW800, .sup.72Ga.sub.y-DOTA-CW800, .sup.89Zr.sub.y-DOTA-CW800, .sup.90Y.sub.y-DOTA-CW800, .sup.95Zr.sub.y-DOTA-CW800, .sup.111In.sub.y-DOTA-CW800, .sup.114In.sub.y-DOTA-CW800, .sup.123I.sub.y-DOTA-CW800, .sup.124I.sub.y-DOTA-CW800, .sup.153Gd.sub.y-DOTA-CW800, .sup.159Gd.sub.y-DOTA-CW800, .sup.177Lu.sub.y-DOTA-CW800, .sup.64Cu.sub.y-DOTA-ZW800, .sup.67Cu.sub.y-DOTA-ZW800, .sup.67Ga.sub.y-DOTA-ZW800, .sup.68Ga.sub.y-DOTA-ZW800, .sup.70Ga.sub.y-DOTA-ZW800, .sup.72Ga.sub.y-DOTA-ZW800, .sup.89Zr.sub.y-DOTA-ZW800, .sup.90Y.sub.y-DOTA-ZW800, .sup.95Zr.sub.y-DOTA-ZW800, .sup.111In.sub.y-DOTA-ZW800, .sup.114In.sub.y-DOTA-ZW800, .sup.123I.sub.y-DOTA-ZW800, .sup.124I.sub.y-DOTA-ZW800, .sup.153Gd.sub.y-DOTA-ZW800, .sup.159Gd.sub.y-DOTA-ZW800, .sup.177Lu.sub.y-DOTA-ZW800, .sup.64Cu.sub.y-NOTA-HQ4, .sup.67Cu.sub.y-NOTA-HQ4, .sup.67Ga.sub.y-NOTA-HQ4, .sup.68Ga.sub.y-NOTA-HQ4, .sup.70Ga.sub.y-NOTA-HQ4, .sup.72Ga.sub.y-NOTA-HQ4, .sup.89Zr.sub.y-NOTA-HQ4, .sup.90Y.sub.y-NOTA-HQ4, .sup.95Zr.sub.y-NOTA-HQ4, .sup.111In.sub.y-NOTA-HQ4, .sup.114In.sub.y-NOTA-HQ4, .sup.123I.sub.y-NOTA-HQ4, .sup.124I.sub.y-NOTA-HQ4, .sup.153Gd.sub.y-NOTA-HQ4, .sup.159Gd.sub.y-NOTA-HQ4, .sup.177Lu.sub.y-NOTA-HQ4, .sup.64Cu.sub.y-NOTA-HQ5, .sup.67Cu.sub.y-NOTA-HQ5, .sup.67Ga.sub.y-NOTA-HQ5, .sup.68Ga.sub.y-NOTA-HQ5, .sup.70Ga.sub.y-NOTA-HQ5, .sup.72Ga.sub.y-NOTA-HQ5, .sup.89Zr.sub.y-NOTA-HQ5, .sup.90Y.sub.y-NOTA-HQ5, .sup.95Zr.sub.y-NOTA-HQ5, .sup.111In.sub.y-NOTA-HQ5, .sup.114In.sub.y-NOTA-HQ5, .sup.123I.sub.y-NOTA-HQ5, .sup.124I.sub.y-NOTA-HQ5, .sup.153Gd.sub.y-NOTA-HQ5, .sup.159Gd.sub.y-NOTA-HQ5, .sup.177Lu.sub.y-NOTA-HQ5, .sup.64Cu.sub.y-NOTA-CW800, .sup.67Cu.sub.y-NOTA-CW800, .sup.67Ga.sub.y-NOTA-CW800, .sup.68Ga.sub.y-NOTA-CW800, .sup.70Ga.sub.y-NOTA-CW800, .sup.72Ga.sub.y-NOTA-CW800, .sup.89Zr.sub.y-NOTA-CW800, .sup.90Y.sub.y-NOTA-CW800, .sup.95Zr.sub.y-NOTA-CW800, .sup.111In.sub.y-NOTA-CW800, .sup.114In.sub.y-NOTA-CW800, .sup.123I.sub.y-NOTA-CW800, .sup.124I.sub.y-NOTA-CW800, .sup.153Gd.sub.y-NOTA-CW800, .sup.159Gd.sub.y-NOTA-CW800, .sup.177Lu.sub.y-NOTA-CW800, .sup.64Cu.sub.y-NOTA-ZW800, .sup.67Cu.sub.y-NOTA-ZW800, .sup.67Ga.sub.y-NOTA-ZW800, .sup.68Ga.sub.y-NOTA-ZW800, .sup.70Ga.sub.y-NOTA-ZW800, .sup.72Ga.sub.y-NOTA-ZW800, .sup.89Zr.sub.y-NOTA-ZW800, .sup.90Y.sub.y-NOTA-ZW800, .sup.95Zr.sub.y-NOTA-ZW800, .sup.111In.sub.y-NOTA-ZW800, .sup.114In.sub.y-NOTA-ZW800, .sup.123I.sub.y-NOTA-ZW800, .sup.124I.sub.y-NOTA-ZW800, .sup.153Gd.sub.y-NOTA-ZW800, .sup.159Gd.sub.y-NOTA-ZW800, .sup.177Lu.sub.y-NOTA-ZW800, and combinations thereof, wherein y∈[1,2,3,4].

12. A drug dosage for treatment of cancers selected from esophagus, pharynx and larynx, lung, brain, and intestines, comprising an effective amount of the system of claim 1.

13. (canceled)

14. The drug dosage according to claim 12, comprising an amount of 0.1-1000 nMole system/kg body weight and provided in a physiological solution of 1-50 ml.

15. The drug dosage according to claim 14 for thermal-therapy, the therapy comprising an increase of an internal temperature of the living tumor cells, to an internal temperature of at least 42° C.

Description

SUMMARY OF FIGURES

[0038] FIG. 1a-g shows cyanines, FIG. 2a-b chelators, and FIG. 3 a complex.

DETAILS OF THE FIGURES

[0039] FIG. 1a-g shows chemical structures of various cyanines. FIGS. 1a-d are cyanines according to the invention, FIGS. 1e-1g according to labels of the prior art.

[0040] FIG. 2a-b shows chemical structures of DOTA and NOTA.

[0041] FIG. 3 shows a cyanine-DOTA complex.

Examples

[0042] Clinical Trials

[0043] Various clinical trials are performed. For some cancers, namely lung cancer, esophagus cancer, brain cancer, larynx/pharynx cancer, and cancer of the intestines populations of patients are followed during treatment, therapy and diagnosis.

[0044] At the University Hospital Tubingen (UKT) various clinical trials are performed with the present targeting system as both diagnostic and therapeutic medicine for esophagus-, brain-, pharynx- and larynx-, lung-, and intestines-cancer. In this clinical trials cancer patients are followed during protocols of diagnosis, treatment and therapy.

[0045] For the diagnostic treatment the chelator is labeled with a radionuclide, like Zirconium, Gallium, Gadolinium, or Copper, and intravenously administered to the patient followed by medical imaging with a PET-, SPECT- or MRI-imaging device. Diagnostic treatment of necro-sis results in the detection, localization and quantify of necrotic tissue in the human body.

[0046] For the radio-therapeutic treatment the chelator is labeled with a radionuclide like Copper or Lutetium and administered to the patient. The radionuclide radiates the living tumor-cells from within the tumor, as it is bound to the necrotic tumor cores.

[0047] For the Hyperthermia-treatment the chelator is labeled with a magnetic molecule like gadolinium and administered to the patient intravenously. As the gadolinium is bound to the necrotic cores in the tumor, the surrounding living tumor is selectively heated with an MRI-imaging device for increasing the tumor cells to 42° C. or more, which leads to increase of living tumor cells.

Results

[0048] For all trials initial results indicate that the present targeting system increases necrosis at a location of the respective cancers.

[0049] In addition it has been found that the present system can be used to establish the effect of a further treatment, such as immunotherapy, chemotherapy, proton therapy, and radiotherapy, by using the targeting system to attach to the necrotic cells formed as a result of the further treatment. Such is important, as now in an early stage an effect of the further treatment can be established; if no effect or a small effect is visible, the further treatment can be stopped.

[0050] The present targeting system itself is also effective as radiotherapy, as the radionuclide of the system increases local necrosis, as is intended.

[0051] As the present system can be used in very low dosage regimes, no side-effects are observed. In addition it has been confirmed that the present system can be cleared form the human body to a high extent.

[0052] It is noted that a healthy human body does not contain necrotic tissue, which means that when necrosis is detected by the present targeting system this indicates a pathological situation like stroke, myocardial infarction, osteo-arthritis and/or a aggressively growing tumor. Aggressively growing (malign) tumors and/or metastases develop a necrotic core starting at a diameter of 3 mm or more. Detecting necrosis in a human body is relevant because based on this outcome medical professionals can diagnose medical issues, determine treatment options and make medical relevant decisions of which the patient can benefit.

[0053] In addition it has been found that the present system can be used to establish the effect of a further treatment, such as immunotherapy, chemotherapy, by using the targeting system to attach to the necrotic cells formed as a result of the further treatment. Such is important, as now in an early stage an effect of the further treatment can be established; if no effect or a small effect is visible, the further treatment can be stopped.

[0054] The present targeting system provides a new early stage method to determine the efficacy of the treatment of aggressively growing (malign) tumors. The outcome and results of conventional therapies like chemotherapy and radio-therapy, but also new therapies like immune-, brachy- or proton-therapy is only available after multiple treatments. Moreover, the outcome of chemo- and immunotherapy is only known after multiple treatments over a longer period of time.

[0055] Today shrinkage and decrease of volume of the tumor are indications that a treatment is effective. Fact is that in average chemotherapies are costly but only effective in a minority of the cases. With the present targeting system necrosis in the tumor is quantified before (T=0) and shortly after (T=1) the administration of the chemo- or immunotherapy. The delta of the radioactive signal between T=0 and T=1 reflects the efficacy of the administered therapy. Implementing this application with the present targeting system provides a reduction of the ineffective treatments with 35% or more. Besides improving quality of life by avoiding severe treatments of patients which do not have to suffer from a treatment which does not provide the desired effect, the cost reduction of cancer treatment is tremendous. Cancer treatment (direct and side-effect treatment) represent 75% or more of the total budget for drugs and treatments in an average hospital. Possible reductions in costs of care and medicines in the Western world alone represent at least € 2 Billions.

[0056] The present targeting system itself is also effective as radiotherapy, as the radionuclide of the system increases local necrosis by killing living tumor-cells with nuclear radiation, as is intended. It is found that typically a volume of tumor-cells is reduced by 50% or more, and often these are not visible anymore. In addition the present treatment provides sufficient control of the tumor, and limits further development thereof, such that patients require on regular treatment at the most; hence patients can now be treated comparable to other long-term diseases and continue mostly or fully with their lives.

[0057] As the present system can be used in very low dosage regimes, the treatment is targeted and limited to the tumor and no side-effects are observed. In addition it has been confirmed that the present system binds to the necrotic core of tumors and the unbound compounds can be cleared from the human body to a high extent within a maximum of 24-hours after administration. This new hyperthermia treatment options provides important new treatment options for non-resectable or non-treatable aggressively growing (malign) tumors. This new targeted in-tumor radiotherapy treatment provides important new options for non-resectable or non-treatable aggressively growing (malign) tumors, such as the ones claimed.

[0058] The present targeting system itself is also effective as thermal-therapy, the treatment of the iron-labelled chelator with MRI results in the increase of the internal temperature of the living tumor cells. After the internal temperature of these cells is 42 □C, or higher, this treatment results in the death of this tumor cells. This new form of hyperthermia treatment provides important new treatment options for non-receptable or non-treatable aggressively growing (malign) tumors.

[0059] Study results show an increase of dead (effectively treat-ed) tumor in 40-60% of tumors (as is 35% on average for to-day's chemotherapy). Repetitive treatments with present targeting system for the same tumor show increase of tumor death by 40-60% for each treatment-cycle that can add up to eradicating all of living cells in a tumor.