SSTR-targeted conjugates and particles and formulations thereof
Conjugates of an active agent such as DM1 attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.
1. A method of treating tumor of a subject, comprising conducting a Somatostatin Analog Radioisotope Imaging (SARI) scanning on the subject, wherein the SARI scanning comprises administering a radioisotope linked to a somatostatin analog, and administering a pharmaceutical composition comprising a conjugate and at least one excipient to the subject if the SARI result is positive, wherein the conjugate has a structure of
and wherein the dosage of Conjugate 57 is between 0.1 mg/kg to 1 mg/kg.
2. The method of claim 1 , wherein the radioisotope is 111 In, 68 Ga, or 99m Tc.
3. The method of claim 1 , wherein the SARI scanning comprises administering a 111 In pentetreotide.
4. The method of claim 1 , wherein the SARI scanning comprises administering 68 Ga linked to a somatostatin analog.
5. The method of claim 1 , wherein the SARI scanning is conducted with single-photon emission computed tomography (SPECT) or concurrent positron emission tomography (PET) and Computed tomography (CT).
6. The method of claim 1 , further comprising administering at least one additional active agent.
7. The method of claim 6 , wherein the additional active agent is a drug for treating nausea, vomiting, diarrhea, constipation, anemia, neutropenia, or a somatostatin analog.
8. The method of claim 1 , wherein the tumor is a neuroendocrine tumor (NET).
9. The method of claim 8 , wherein the tumor selected from the group consisting of gastroenteropancreatic (GEP), lung, prostate, and thymus neuroendocrine tumor.
10. The method of claim 9 , wherein the tumor is small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC) of the lung.