Compositions and method for multimodal imaging

• US 8,703,097 B2
• Filed: 02/10/2006
• Issued: 04/22/2014
• Est. Priority Date: 02/11/2005
• Status: Active Grant

• Current Assignee: University Health Network
• Original Assignee: University Health Network
• Inventors: Jaffray, David, Allen, Christine, Zheng, Jinzi, Reilly, Raymond Matthew, Perkins, Gregory Jason
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US11/816,054
• Publication Number:
  US 20080206131A1
• Time in Patent Office: 2,993 Days
• Field of Search: 424/9, 424/9.4, 424/9.51, 424/9.6, 424/450, 514/16, 514/4, 514/283
• US Class Current: 424/1.21
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 6/00 Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment instruments measuring radiation intensity for application in the field of nuclear medicine, e.g. in vivo counting, G01T1/161; apparatus for taking X-ray photographs G03B42/02
• CPC Class Codes: A61B 6/5247 combining images from an ionising-radiation diagnostic technique and a non-ionising radiation diagnostic technique, e.g. X-ray and ultrasound
• CPC Class Codes: A61B 8/00 Diagnosis using ultrasonic, sonic or infrasonic waves imaging of objects using sonar G01S15/00
• CPC Class Codes: A61B 8/5238 for combining image data of patient, e.g. merging several images from different acquisition modes into one image for image registration algorithms G06T7/30
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/04 X-ray contrast preparations
• CPC Class Codes: A61K 49/0466 Liposomes, lipoprotein vesicles, e.g. HDL or LDL lipoproteins, phospholipidic or polymeric micelles
• CPC Class Codes: A61K 49/1812 liposomes, polymersomes, e.g. immunoliposomes
• CPC Class Codes: A61K 51/1234 Liposomes
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911

Abstract

Provided are signal modifying compositions for medical imaging comprising a carrier and two or more signal modifying agents specific for two or more imaging modalities. The compositions are characterized by retention efficiency, with respect to the signal modifying agents, which enables prolonged contrast imaging without significant depletion of the signal modifying agents from the carrier. The carriers of the present invention are lipid based or polymer based, the physico-chemical properties of which can be modified to entrap or chelate different signal modifying agents and mixtures thereof and to target specific organs or tumors or tissues within a mammal.

Claims

1. A composition for imaging of a biological tissue, said composition comprising:

a) two or more separate and unlinked signal modifying agents, each of said agents being specific for at least one imaging modality and each of said agents being specific for a different imaging modality; and

b) a colloidal carrier comprising said two or more signal modifying agents wherein said carrier retains a sufficient amount of said agents for a time sufficient to acquire in vivo imaging data from each of the two or more signal modifying agents using said composition, and said colloidal carrier is a liposome comprising at least one lipid, cholesterol, and at least one pegylated lipid; and

wherein said composition is specific for two or more imaging modalities selected from magnetic resonance imaging (MRI), X-ray, positron emission tomography (PET), computed tomography (CT), autoradiography, single-photon emission computed tomography (SPECT), fluoroscopy, optical imaging, fluorescence imaging, bioluminescence imaging and combinations thereof and each of the signal modifying agents is present at a different concentration that is sufficient to acquire in vivo imaging data from an imaging modality for which said signal modifying agent is specific, wherein said composition comprises i) a signal modifying agent specific for MRI comprising gadoteridol and a signal modifying agent specific for CT comprising iohexol, ii) a signal modifying agent specific for optical imaging comprising a fluorophore and a signal modifying agent specific for CT comprising iohexol or iii) a signal modifying agent specific for optical imaging comprising a fluorophore and a signal modifying agent specific for MRI comprising gadoteridol.

2. The composition as claimed in claim 1 wherein said carrier has a retention efficiency of about 10 to 100% for a time sufficient to acquire imaging data.

3. The composition as claimed in claim 1 wherein said carrier has a retention efficiency of about 80 to 100% for a time sufficient to acquire imaging data.

4. The composition as claimed in claim 1 wherein said composition provides signal modification for image data acquisition in said biological tissue for a predetermined amount of time.

5. The composition as claimed in claim 4 wherein said predetermined amount of time is between about 1 minute and about 14 days.

6. The composition as claimed in claim 4 wherein said predetermined amount of time is between about 5 minutes and about 7 days.

7. The composition as claimed in claim 1 wherein said two or more separate and unlinked signal modifying agents are specific for imaging modalities selected from MRI, CT, optical imaging and combinations thereof.

8. The composition as claimed in claim 1 wherein said two or more separate and unlinked signal modifying agents are specific for imaging modalities selected from MRI, CT, PET, SPECT, optical imaging and combinations thereof.

9. The composition as claimed in claim 8 wherein said signal modifying agents specific for MRI comprise gadolinium, said signal modifying agents specific for CT comprise iodine, said signal modifying agents specific for PET and SPECT comprise a positron emitting radioisotope or a gamma ray emitting radioisotope and said signal modifying agents specific for optical imaging comprise a fluorophore.

10. The composition as claimed in claim 1 wherein said lipid is phosphatidylcholine (PC) and said PEGylated lipid is polyethylene glycol-phophatidylethanolamine (PEG-PE).

11. The composition as claimed in claim 10 wherein said PC:

CHOL;

PEG-PE are in a molar ratio of about 55;

40;

5.

12. The composition as claimed in claim 11 wherein said PC is Dipalmitoyl-PC(DPPC) and said PEG-PE is PEG2000-Distearoyl-PE(PEG2000-DSPE).

13. The composition as claimed in claim 1 wherein said liposomes have a diameter of between about 30 nm and about 1000 nm.

14. The composition as claimed in claim 13 wherein said liposomes have a diameter of between about 30 nm and about 500 nm.

15. The composition as claimed in claim 14 wherein said liposomes have a diameter of between about 50 nm and 150 nm.

16. The composition as claimed in claim 1 wherein said carrier is targeted to a specific target within a mammal.

17. The composition as claimed in claim 16 wherein said targeting is achieved through control of said carrier'"'"'s physico-chemical properties.

18. The composition as claimed in claim 16 wherein said carrier comprises one or more recognition molecules to achieve targeting.

19. The composition as claimed in claim 18 wherein said target is a cell population.

20. The composition as claimed in claim 18 wherein said one or more recognition molecules are selected from antibodies, receptors/ligands, carbohydrates, proteins and peptide fragments.

21. The composition as claimed in claim 1 further comprising a therapeutic agent.

22. The composition as claimed in claim 21 wherein said therapeutic agent is selected from anticancer, antimicrobial, antifungal and antiviral agents.

23. A method for registering images obtained from two or more imaging modalities said method comprising:

a) administering to a mammal a composition as claimed in claim 1, each agent being specific for at least one of said two or more imaging modalities;

b) obtaining an image of one or more regions of interest in said mammal using each of said two or more imaging modalities; and

c) comparing the images obtained in b) to derive complementary information from said one or more regions of interest.

24. The method as claimed in claim 23 wherein said complementary information is selected from anatomical information, molecular information, functional information, physiological information and combinations thereof.

25. The composition of claim 1, wherein each of signal modifying agents is present at a different concentration that is sufficient to acquire in vivo imaging data from an imaging modality for which said signal modifying agent is specific in a single administration.

26. The composition of claim 1, wherein the liposome releases <

9% of each of said signal modifying agents over 15 days when dialyzed under sink conditions against HBS at 4°

C. or 37°

C.

27. The composition of claim 1, wherein said two or more separate and unlinked signal modifying agents that are each specific for at least one imaging modality independently have differing loading efficiencies for imaging modalities.

28. The composition of claim 1, wherein said two or more separate and unlinked signal modifying agents have independent and different release profiles.

29. A method for imaging one or more regions of interest in a mammal said method comprising:

a) administering to said mammal the composition as claimed in claim 1;

b) waiting for a time sufficient for said composition to reach said region of interest; and

c) obtaining two or more images of said one or more regions of interest.

30. The method as claimed in claim 29 wherein said step of waiting further comprises waiting for a time sufficient for said composition to substantially clear from a predetermined region.

31. The method as claimed in claim 29 wherein said regions of interest comprises an abnormality and wherein said abnormality is detected in said images.

32. The method as claimed in claim 31 wherein the abnormality is a tumor.

33. The method as claimed in claim 29 further comprising the step of estimating a pharmacokinetic profile of said composition.

34. The method as claimed in claim 33 further comprising the step of designing an administration regimen based on said pharmacokinetic profile.

35. The method as claimed in claim 34 wherein said administration regimen is applied to a patient in need thereof.

36. The method as claimed in claim 35 wherein progress of said administration regimen is followed over time by obtaining one or more images after said regimen is started.

37. The method as claimed in claim 35 wherein said therapeutic regimen is a regimen for treating cancer.

38. The method as claimed in claim 37 wherein said regimen is selected from surgery, radiotherapy, chemotherapy, cell therapy, gene therapy and hyperthermia.

39. The method as claimed in claim 34 wherein the composition further comprises a therapeutic agent and said administration regimen is a therapeutic regimen.

40. A composition for imaging of a biological tissue, said composition comprising:

a) two or more separate and unlinked signal modifying agents, each of said agents being specific for at least one imaging modality and each of said agents being specific for a different imaging modality; and

b) a colloidal carrier comprising said two or more signal modifying agents wherein said carrier retains a sufficient amount of said agents for a time sufficient to acquire in vivo imaging data from each of the two or more signal modifying agents using said composition, and said colloidal carrier is a liposome comprising at least one lipid, cholesterol, and at least one pegylated lipid; and

wherein said composition is specific for two or more imaging modalities selected from magnetic resonance imaging (MRI), X-ray, positron emission tomography (PET), computed tomography (CT), autoradiography, single-photon emission computed tomography (SPECT), fluoroscopy, optical imaging, fluorescence imaging, bioluminescence imaging and combinations thereof and each of the signal modifying agents is present at a different concentration that is sufficient to acquire in vivo imaging data from an imaging modality for which said signal modifying agent is specific, wherein one signal modifying agent is specific for MRI and comprises gadolinium at a concentration >

5 mmol/L and wherein another signal modifying agent is specific for CT and comprises iodine at a concentration of at least 1 mg/ml.

41. A method for imaging one or more regions of interest in a mammal said method comprising the steps of:

a) administering to said mammal the composition of claim 40;

b) waiting for a time sufficient for said composition to reach said region of interest; and

c) obtaining two or more images of said one or more regions of interest.