Lipid-based systems for targeting diagnostic agents

• US 7,368,254 B2
• Filed: 04/11/2001
• Issued: 05/06/2008
• Est. Priority Date: 04/12/2000
• Status: Expired due to Fees

• Current Assignee: LiPlasome Pharma A/S
• Original Assignee: LiPlasome Pharma A/S
• Inventors: Davidsen, Jesper, Jorgensen, Kent, Mouritsen, Ole G., Frokj.ae butted.r, Sven, Vermehren, Charlotte
• Primary Examiner(s): FETTEROLF, BRANDON J
• Application Number:
  US10/239,515
• Publication Number:
  US 20030175205A1
• Time in Patent Office: 2,582 Days
• Field of Search: 514/642, 514/144, 514/557, 424/1.37, 424/1.65, 424/9.1, 424/9.3, 424/9.32, 424/9.321
• US Class Current: 435/7.23
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/04 Amoebicides
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to targeting of diagnostic agents by use of lipid-based compositions. The invention is useful in the diagnosis of various disorders which are associated with or resulting from increased levels of extracellular PLA₂ activity in the diseased tissue, e.g. cancer, infectious, and inflammatory conditions.

Claims

1. A method for identifying malignant tissue in a mammal, wherein said malignant tissue is a member selected from the group consisting of lung cancer, ovarian cancer and sarcoma tissue, said method comprising:

a) administering a lipid-based system comprising a lipid derivative and a label to an individual suspected of having a malignant disease characterised by having an elevated PLA₂ level whereby said label is released from said lipid derivative to the malignant tissue, and

b) detecting said label, thereby identifying said malignant tissue, and

wherein said lipid derivative constitutes 50-100 mol % of said lipid-based system, and

wherein said lipid derivative has the following formula;

2. A method according to claim 1, wherein the label is selected from the group consisting of ¹¹¹In, ^99mTc ⁶⁷Ga, ¹¹C, Gd, Mn, iron oxide, argon, nitrogen, Iodine, bromine and barium.

3. A method according to claim 1, wherein R² is an aliphatic group of a length of at least 7 carbon atoms.

4. A method according to claim 3, wherein R² is a group of the formula Y¹Y².

5. A method according to claim 1, wherein the lipid-based system is in the form of liposomes wherein a drug is incorporated.

6. A method according to claim 1, wherein the label is covalently linked to the lipid derivative.

7. A method according to claim 1, wherein the malignant tissue is the primary tumour.

8. A method according to claim 1, wherein the malignant tissue is metastatic cells originating from the primary tumour.

9. A method according to claim 1, wherein the label is detected by a method selected from the group consisting of positron emission tomography (PET), X-ray, gamma-scintigraphy, magnetic resonance (MR) imaging, computed tomography (CT) imaging and ultrasonography.

10. The method according to claim 1, wherein:

R¹ and R² are independently an aliphatic group of the formula (CH₂)_nCH₃ wherein n is an integer from 11-29.

11. The method according to claim 10, wherein n is an integer of from 14-16.

12. The method according to claim 4, wherein R³is a member selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine;

phosphatidyl inositol and phosphatidyl glycerol.

13. The method according to claim 10, wherein R³ is a member selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol and phosphatidyl glycerol.

14. The method according to claim 11, wherein R³ is a member selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol and phosphatidyl glycerol.

15. The method according to any one of claims 10-14, wherein the label is covalently linked to the lipid derivative.

16. The method according to claim 1, wherein said label is quantitatively detected and the amount of said malignant tissue in said mammal is quantified.

17. The method according to claim 16, wherein the label is quantified by a method selected from the group consisting of positron emission tomography (PET), X-ray, gamma-scintigraphy, magnetic resonance (MR) imaging, computed tomography (CT) imaging and ultrasonography.