# US 2014/0193330 A1 · Compositions and methods for multimodal imaging

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- Number: US 2014/0193330 A1
- Document ID: US20140193330A1
- Status: Published application
- Kind: A1
- Application number: 14/205,670
- Filed: 2014-03-12
- Published: 2014-07-10
- Earliest claimed: 2005-02-11
- Assignees: University Health Network
- Applicants: University Health Network
- Inventors: David JAFFRAY; Christine ALLEN; Jinzi ZHENG; Raymond Matthew REILLY; Gregory Jason PERKINS
- Web page: https://patentgrep.com/patent/US20140193330A1

## CPC

- A61K 49/04: X-ray contrast preparations
- A61B 5/415: {the glands, e.g. tonsils, adenoids or thymus}
- A61B 5/418: {lymph vessels, ducts or nodes}
- 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)
- A61B 6/5247: {combining images from an ionising-radiation diagnostic technique and a non-ionising radiation diagnostic technique, e.g. X-ray and ultrasound}
- A61B 8/5238: {for combining image data of patient, e.g. merging several images from different acquisition modes into one image}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 49/0466: {Liposomes, lipoprotein vesicles, e.g. HDL or LDL lipoproteins, phospholipidic or polymeric micelles}
- A61K 49/1812: {liposomes, polymersomes, e.g. immunoliposomes}
- A61K 51/1234: {Liposomes}
- A61B 8/00: Diagnosis using ultrasonic, sonic or infrasonic waves
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

There is provided signal modifying compositions for medical imaging comprising a carrier and signal modifying agents specific for two or more imaging modalities. The compositions are characterized by retention efficiency, with respect of the signal modifying agents that enables prolonged contrast imaging without significant depletion of the signal modifying agent 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

### Claim 1

A composition for imaging of a biological tissue, said composition comprising:
a) two or more 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 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 4)

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

### Claim 6 (depends on 4)

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

### Claim 7 (depends on 1)

The composition as claimed in claim 1 wherein said signal modifying agents are selected from iodine, gadolinium, manganese, iron, perfluorocarbons, alpha, beta, gamma and positron emitting radiotracers and a fluorophore.

### Claim 8 (depends on 1)

The composition as claimed in claim 1 wherein said carrier is a lipid based colloidal carrier.

### Claim 9 (depends on 8)

The composition as claimed in claim 8 wherein said lipid based colloidal carrier is selected from liposomes and micelles.

### Claim 10 (depends on 9)

The composition as claimed in claim 9 wherein said lipid based colloidal carrier is a liposome and wherein said two or more signal modifying agents are specific for imaging modalities selected from MRI, CT, optical imaging and combinations thereof.

### Claim 11 (depends on 10)

The composition as claimed in claim 10 wherein said signal modifying agents specific for MRI, CT and optical imaging comprise gadolinium, iodine and a fluorophore respectively.

### Claim 12 (depends on 9)

The composition as claimed in claim 9 wherein said lipid based colloidal carrier is a liposome and wherein said two or more signal modifying agents are specific for imaging modalities selected from MRI, CT, PET, SPECT, optical imaging and combinations thereof.

### Claim 13 (depends on 12)

The composition as claimed in claim 12 wherein said signal modifying agents specific for MRI, CT, PET, SPECT and optical imaging comprise gadolinium, iodine, a positron emitting radioisotope, a gamma ray emitting radioisotope and a fluorophore respectively.

### Claim 14 (depends on 9)

The composition as claimed in claim 9 wherein said liposomes comprise one or more lipids, cholesterol (CHOL) and one or more PEGylated lipids.

### Claim 15 (depends on 14)

The composition as claimed in claim 14 wherein said one or more lipids is a neutral lipid.

### Claim 16 (depends on 15)

The composition as claimed in claim 15 wherein said neutral lipid is phosphatidylcholine (PC) and said PEGylated lipid is polyethylene glycol-phosphatidylethanolamine (PEG-PE).

### Claim 17 (depends on 16)

The composition as claimed in claim 16 wherein said PC:CHOL:PEG-PE are in a molar ratio of about 55:40:5.

### Claim 18 (depends on 17)

The composition as claimed in claim 17 wherein said PC is Dipalmitoyl-PC(DPPC), said PEG-PE is PEG2000-Distearoyl-PE(PEG2000-DSPE), wherein said signal modifying agent specific for MRI comprises gadoteridol and wherein said signal modifying agent specific for CT comprises iohexyl.

### Claim 19 (depends on 9)

The composition as claimed in claims 9 wherein said liposomes have a diameter of between about 30 nm and about 1000 nm.

### Claim 20 (depends on 9)

The composition as claimed in claims 9 wherein said liposomes have a diameter of between about 30 nm and about 500 nm.

### Claim 21 (depends on 9)

The composition as claimed in claims 9 wherein said liposomes have a diameter of between about 50 nm and 150 nm.

### Claim 22 (depends on 1)

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

### Claim 23 (depends on 22)

The composition as claimed in claim 22 wherein said targeting is achieved through control of said carrier's physico-chemical properties.

### Claim 24 (depends on 22)

The composition as claimed in claim 22 wherein said carrier comprises one or more recognition molecules to achieve targeting.

### Claim 25 (depends on 24)

The composition as claimed in claim 24 wherein said target is a cell population.

### Claim 26 (depends on 24)

The composition as claimed in claim 24 wherein said one or more recognition molecules are selected from antibodies, receptors/ligands, carbohydrates, proteins and peptide fragments.

### Claim 27 (depends on 1)

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

### Claim 28 (depends on 27)

The composition as claimed in claim 27 wherein said therapeutic agent is selected from anticancer, antimicrobial, antifungal and antiviral agents.

### Claim 29 (depends on 1)

Use of the composition as claimed in claim 1 for imaging one or more regions of interest in a mammal using 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.

### Claim 30 (depends on 29)

The use as claimed in claim 29 wherein said regions of interest comprises an abnormality and wherein said abnormality is detected by said imaging.

### Claim 31 (depends on 30)

The use as claimed in claim 30 wherein said abnormality is a tumor.

### Claim 32 (depends on 29)

The use as claimed in claim 29 wherein said composition is used as a fiducial marker.

### Claim 33 (depends on 1)

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

### Claim 34 (depends on 33)

The method as claimed in claim 33 wherein said step of waiting further comprises waiting for a time sufficient for said composition to substantially clear from a predetermined region.

### Claim 35 (depends on 33)

The method as claimed in claim 33 wherein said regions of interest comprises an abnormality and wherein said abnormality is detected in said images.

### Claim 36 (depends on 35)

The method as claimed in claim 35 wherein the abnormality is a tumor.

### Claim 37

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 any 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.

### Claim 38 (depends on 37)

The method as claimed in claim 37 wherein said complementary information is selected from anatomical information, molecular information, functional information, physiological information and combinations thereof.

### Claim 39 (depends on 33)

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

### Claim 40 (depends on 39)

The method as claimed in claim 39 further comprising the step of designing an administration regimen based on said pharmacokinetic profile.

### Claim 41 (depends on 40)

The method as claimed in claim 40 wherein said administration regimen is applied to a patient in need thereof.

### Claim 42 (depends on 41)

The method as claimed in claim 41 wherein progress of said administration regimen is followed over time by obtaining one or more images after said regimen is started.

### Claim 43 (depends on 40)

The method as claimed in claims 40 wherein the composition further comprises a therapeutic agent and said administration regimen is a therapeutic regimen.
