# US 8,569,482 B2 · Nanoparticulate probe for in vivo monitoring of tissue oxygenation

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- Number: US 8,569,482 B2
- Document ID: US8569482B2
- Status: Granted
- Kind: B2
- Application number: 13/306,565
- Filed: 2011-11-29
- Published: 2012-11-01
- Granted: 2013-10-29
- Earliest claimed: 2003-09-05
- Assignees: The Ohio State University Research Foundation
- Applicants: Periannan Kuppusamy; Vijay Kutala; Jay L. Zweier; Pawel Kwiatkowski
- Inventors: Periannan Kuppusamy; Vijay Kutala; Jay L. Zweier; Pawel Kwiatkowski
- Web page: https://patentgrep.com/patent/US8569482B2

## CPC

- A61K 49/20: containing free radicals {, e.g. trityl radical for overhauser}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61B 5/145: Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value {; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue} (non-radiation detecting or locating of foreign bodies in blood A61B5/06)
- A61B 5/412: {Detecting or monitoring sepsis}
- A61K 49/1896: {not provided for elsewhere, e.g. cells, viruses, ghosts, red blood cells, virus capsides}
- 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

A new class of micro- and nano-particulate paramagnetic spin probes useful for magnetic resonance imaging techniques, including electron paramagnetic resonance (EPR) and magnetic resonance imaging (MRI). The probes are lithium phthalocyanine derivative compounds. Also provided are suspensions and emulsions comprising lithium phthalocyanine derivative probes. Also provided are noninvasive methods for measuring noninvasive methods of measuring oxygen concentration, oxygen partial pressure, oxygen metabolism, and nitric oxide concentration in a specific tissue, organ, or cell in vivo or in vitro.

## Claims

### Claim 1

A method of monitoring cells, comprising:
administering to a subject at least one cell selected from the group consisting of a progenitor cell, mesenchymal cell, myoblast cell, islet cell, and combinations thereof, wherein the at least one cell has at least one probe internalized therein; said at least one probe comprising a compound or a radical thereof of the formula:
wherein R is selected from the group consisting of O(CH2)nCH3, S(CH2)nCH3, O(CH2)nCH2OH, O(CH2)CH2NH2, O(CH2)nCH2SH, and combinations thereof, wherein n is any one of 1-6, and
applying a magnetic resonance technique such that the at least one probe is monitored.

### Claim 2 (depends on 1)

The method as claimed in claim 1 wherein the at least one cell has a plurality of probes internalized therein.

### Claim 3 (depends on 2)

The method as claimed in claim 2 wherein the plurality of probes have a mean particle size of less than about 1 μm.

### Claim 4 (depends on 2)

The method as claimed in claim 2 wherein the plurality of probes have a mean particle size between about 20 nm to about 300 nm.

### Claim 5 (depends on 1)

The method as claimed in claim 1 wherein the magnetic resonance technique is selected from the group consisting of MRI, ESR, EPR, EPRI, and PEDRI.

### Claim 6 (depends on 1)

The method as claimed in claim 1 further comprising applying a magnetic resonance technique such that at least one of oxygen concentration, oxygen partial pressure, oxygen metabolism, or nitrogen oxide concentration in the at least one cell is determined.

### Claim 7 (depends on 1)

The method as claimed in claim 1 comprising monitoring at least one of intercellular oxygenation, cellular hypoxia, cellular hyperoxia, cell division, cellular migration, cellular retention, or metastasis of the at least one cell.

### Claim 8 (depends on 7)

The method as claimed in claim 7 wherein the step of monitoring is performed such that the efficacy of the at least one cell is determined.

### Claim 9 (depends on 1)

The ethod as claimed in claim 1 further comprising one of administering a therapeutic to the at least one of a tissue or an organ of the subject and monitoring the at least one cell to determine the efficacy of the therapeutic and technique.

### Claim 10 (depends on 1)

The method as claimed in claim 1 wherein the at least one cell comprises a plurality of cells selected from the group consisting of progenitor cells, mesenchymal cells, myoblast cells, islet cells, and combinations thereof.

### Claim 11 (depends on 1)

The method as claimed in claim 1 wherein the at least cell is administered to the subject intravenously as a suspension or an emulsion.

### Claim 12 (depends on 1)

The method as claimed in claim 1 wherein the at least one cell is administered to the subject by implanting the at least one cell into a tissue or an organ of the subject.

### Claim 13 (depends on 12)

The method as claimed in claim 12 wherein the at least one cell is administered directly to one of a site of an injury of a tissue or a site of an injury of an organ of the subject.

### Claim 14 (depends on 13)

The method as claimed in claim 13 wherein the site of the injury of the organ of the subject comprises scar tissue on the heart of the subject.

### Claim 15 (depends on 1)

The method as claimed in claim 1 wherein the subject is an animal.

### Claim 16 (depends on 1)

The method as claimed in claim 1 wherein the subject is a human.
