Liposomes useful for non-invasive imaging and drug delivery

Patent metadata

Field	Value
Publication number	US-2016303264-A1
Application number	US-201415031643-A
Country	US
Kind code	A1
Filing date	Oct 23, 2014
Priority date	Oct 23, 2013
Publication date	Oct 20, 2016
Grant date	—

Abstract

The present invention relates to liposomes useful for diagnosis and/or therapy of a target site, such as cancerous tissue. The compositions and methods disclosed herein find particular use in diagnosing and imaging cancerous tissue. The present invention provides a new diagnostic tool for the utilization of positron emission tomography (PET) computed tomography imaging technique.

First claim

What is claimed is:

1 . A composition comprising 64 Cu-loaded HER2-targeted immunoliposomes containing doxorubicin, wherein the 64 Cu-loaded HER2-targeted immunoliposomes comprise hydrogenated soy phosphatidylcholine (HSPC), cholesterol, and poly(ethylene glycol) (PEG)-derivatized distearoylphosphatidylethanolamine (PEG-DSPE) at a 3:1:0.05 molar ratio.

2 . The composition of claim 1 , wherein the composition is adapted for administration to a human patient at a dose of at least 0.028, at least 3, at least 4, at least 5, at least 6, or 7 mg/m 2 of doxorubicin.

3 . The composition of claim 1 , wherein the 64 Cu-loaded HER2-targeted immunoliposomes comprise a gradient-loadable chelator.

4 . The composition of claim 3 , wherein the chelator is 4-DEAP-ATSC.

5 . The composition of claim 1 , wherein the composition comprises at least 1, at least 5, at least 10, about 10.8, about 12, or about 15 mCi of 64 Cu.

6 . A method of imaging a lesion in a patient, the method comprising:
(a) administering to the patient an injection comprising a preparation of 64 Cu-loaded HER2-targeted immunoliposomes, the immunoliposomes having an average diameter of 75-110 nm, and a dose of 3-5 mg/m 2 doxorubicin; (b) obtaining a PET scan of a region of the patient, the region comprising the location of the lesion within 48 hours following the injection.

7 . The method of claim 6 , wherein the starting dose of 64 Cu-loaded HER2-targeted immunoliposomes ranges from 320-440 MBq.

8 . The method of claim 6 , wherein the 64 Cu-loaded HER2-targeted immunoliposomes comprise a gradient-loadable chelator.

9 . The method of claim 8 , wherein the chelator is 4-DEAP-ATSC.

10 . The method of claim 6 , wherein the lesion is a benign tumor or a malignant tumor.

11 . The method of claim 10 , wherein the lesion is a malignant brain tumor.

12 . The method of claim 6 , wherein the dose of 64 Cu-loaded HER2-targeted immunoliposomes is formulated to deliver to the patient, when administered, 10.8 (+/−15%) mCi of 64 Cu.

13 . The method of claim 6 , wherein the PET scan is obtained within 24 hours, within 12 hours, within six hours, within 3 hours, within 2 hours, or within 1 hour following the injection.

14 . A method of treating and imaging a patient, the method comprising:
(a) administering to the patient a first injection comprising HER2-targeted immunoliposomal doxorubicin that does not comprise detectable levels of 64 Cu, the first injection administered at a dose of 30 mg/m 2 of doxorubicin (doxorubicin HCl equivalent) in a doxorubicin encapsulated HER2-targeted immunoliposome; (b) at between one and 6 hours following the first injection, administering to the patient a second injection comprising 64 Cu-loaded HER2-targeted immunoliposomal doxorubicin, containing a dose of doxorubicin of at least 3, at least 4, at least 5, at least 6, or 7 mg/m 2 , said second injection comprising between 9.18 mCi and 12.42 mCi of 64 Cu; and (c) obtaining at least two scans selected from the group consisting of PET scans, CT scans or a combination thereof, of a region of pathology in the patient, wherein each scan is obtained at a different time point, and wherein time elapsed from the injection of (a) until a final scan of the at least two scans is obtained is no more than three days.

15 . The method of claim 14 , wherein the region of pathology is a malignant brain tumor.

16 . The method of claim 14 , wherein the region of pathology is a metastatic lesion selected from the group consisting of: a liver metastatic lesion, a bone metastatic lesion, a brain metastatic lesion, a breast metastatic lesion, a skin metastatic lesion, and a sternum metastatic lesion.

17 . The method of claim 14 , wherein the 64 Cu-loaded HER2-targeted immunoliposomal doxorubicin comprises a gradient-loadable 4-DEAP-ATSC chelator.

18 . The method of claim 14 , wherein the first scan is obtained within 3 hours following the second injection.

19 . The method of claim 18 , wherein the first scan is obtained within 2 hours or within 1 hour following the second injection.

20 . The method of claim 14 , wherein the first scan is obtained within 3 hours following the second injection, a second scan is obtained within 18-30 hours following the second injection and a third scan is obtained 18-30 hours following the second injection, but at least 4 hours after the second scan.

21 . The method of claim 14 , wherein the first scan is obtained within 3 hours following the second injection, a second scan is obtained within 42-54 hours following the second injection and an optional third scan is obtained 18-30 hours following the second injection.

22 . A method of treating and imaging a patient, the method comprising:
(a) administering to the patient once on day 1 of a first 21-day treatment cycle: a first injection comprising an amount of doxorubicin contained in 30 mg/m 2 of doxorubicin HCl encapsulated in a MM-302 HER2-targeted doxorubicin immunoliposome that does not comprise detectable levels of 64 Cu; (b) at between one and 6 hours following the first injection, administering to the patient a second injection comprising 64 Cu-loaded HER2-targeted immunoliposomal doxorubicin, containing a dose of doxorubicin of at least 3, at least 4, at least 5, at least 6, or 7 mg/m 2 , said second injection comprising between 9.18 mCi and 12.42 mCi of 64 Cu; and (c) obtaining at least two scans selected from the group consisting of PET scans, CT scans or a combination thereof, of a region of pathology in the patient, wherein each scan is obtained at a different time point, and wherein time elapsed from the injection of (a) until a final scan of the at least two scans is obtained is no more than three days.

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

• Hendriks Bart S
• Lee Helen
• Moyo Victor
• Wickham Thomas

Classifications

• A61K51/1234

  Liposomes · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K51/1051 Primary

  the tumor cell being from breast, e.g. the antibody being herceptin · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K51/1063

  the tumor cell being from stomach or intestines · CPC title