Somatostatin analogs with inhibitory activity to growth hormone release
View Patent ↗Provided are therapeutic and diagnostic somatostatin analogs including radiotherapeutic and radiodiagnostic reagents, and methods of making and use thereof.
1. A method of visualizing malignant cells in a subject comprising administering to the subject a compound selected from the group consisting of 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Asp-NH 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Thr-NH 2 , 4-amino-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH 2 , and D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH 2 and any combination thereof, wherein the compound is radiolabeled.
2. The method of claim 1 , wherein the compound comprises a di- or polyiodinated aromatic modification of a Tyr at position 3.
3. The method of claim 1 , wherein the radioactive element is selected from the group consisting of 188 Re, 186 Re, scandium-47, copper-67, gallium-72, yttrium-90, iodine-125, iodine-131, samarium-153, gadolinium-159, dysprosium-165, holmium-166, ytterbium-175, lutetium-177, rhenium-186, rhenium-188, astatine-211 and bismuth-212.
4. A method of treating a cell proliferative disorder in a subject comprising administering to the subject a compound selected from the group consisting of 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Asp-NH 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Thr-NH 2 , 4-amino-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH 2 , and D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-NH 2 and any combination thereof, wherein the compound is radiolabelled.
5. A method as in claim 4 , wherein the cell proliferative disorder is selected from the group consisting of a tumor, acromegaly, and diabetes.
6. The method of claim 4 , wherein the compound comprises a di- or polyiodinated aromatic modification of a Tyr at position 3.
7. The method of claim 4 , wherein the radioactive element is selected from the group consisting of 188 Re, 186 Re, scandium-47, copper-67, gallium-72, yttrium-90, iodine-125, iodine-131, samarium-153, gadolinium-159, dysprosium-165, holmium-166, ytterbium-175, lutetium-177, rhenium-186, rhenium-188, astatine-211 and bismuth-212.
8. A method of activating SST2 and/or SST5 receptors in a subject comprising administering to said mammal an effective amount of a compound selected from the group consisting of 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Asp-NH 2 , 4-amino-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-D-Thr-N H 2 , 4-amino-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 ; 4-amino-3-iodo-D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Thr-N H 2 , 4-amino-3-iodo-D-Phe-c[Cys-(3-iodo)-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 , and D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Asp-N H 2 and any combination thereof or a pharmaceutically acceptable salt thereof, wherein the compound activates SST2 and/or SST5 receptors in the subject.