# US 7,744,854 B2 · Method for optimizing cancer therapy by monitoring maturation of tumor associated vasculature by selenium

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- Number: US 7,744,854 B2
- Document ID: US7744854B2
- Status: Granted
- Kind: B2
- Application number: 11/728,075
- Filed: 2007-03-23
- Published: 2008-01-24
- Granted: 2010-06-29
- Earliest claimed: 2006-03-24
- Assignees: Health Research, Inc.
- Inventors: Youcef M. Rustum; Arup Bhattacharya; Karoly Toth; Harry K. Slocum; Rami G. Azrak; Sreenivasulu Chintala; Mukund Seshadri; Richard Mazurchuk
- Web page: https://patentgrep.com/patent/US7744854B2

## CPC

- A61K 49/06: Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K 31/282: Platinum compounds
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/66: Phosphorus compounds
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- B24B 49/003: {involving acoustic means}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B24B: MACHINES, DEVICES, OR PROCESSES FOR GRINDING OR POLISHING (grinding of gear teeth B23F, of screw-threads B23G1/36; by electro-erosion B23H; abrasive or related blasting B24C; tools for grinding, buffing or sharpening B24D; polishing compositions C09G1/00; abrasives C09K3/14; electrolytic etching or polishing C25F3/00; grinding arrangements for use on assembled railway tracks E01B31/17); DRESSING OR CONDITIONING OF ABRADING SURFACES; FEEDING OF GRINDING, POLISHING, OR LAPPING AGENTS

## Abstract

This invention provides a method for a method for optimizing the regimen for the administration of chemotherapeutic agents. The method comprises administration of a selenium compound to an individual, monitoring the modulation of tumor vessel maturation (TVM) to identify an optimal time for administration of a chemotherapeutic agent. This invention also provides a method to determine whether or not a tumor is likely to be a responder to chemotherapy. The method comprises administration of a selenium compound to an individual and determining whether or not an increase in TVM is observed. An increased TVM following administration of selenium is an indication that the tumor will likely respond the chemotherapy.

## Claims

### Claim 1

A method for inhibiting the growth of a solid tumor comprising the steps of:
a) administering methylselenocysteine (MSC) and/or seleno-L-methionine (SLM)
b) monitoring blood vessel maturation in the tumor; and
c) upon detection of vessel maturation, administering a therapeutically effective dose of a chemotherapeutic agent.

### Claim 2 (depends on 1)

The method of claim 1, wherein blood vessel maturation is monitored by magnetic resonance imaging.

### Claim 3 (depends on 1)

The method of claim 1, wherein the blood vessel maturation is monitored by immunohistochemical techniques on a biopsy sample of the tumor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the MSC or SLM is administered for at least 3 days before carrying out step b.

### Claim 5 (depends on 3)

The method of claim 3, wherein the MSC or SLM is administered for at least 5 days before carrying out step b.

### Claim 6 (depends on 1)

The method of claim 1, wherein the chemotherapeutic agent is selected from the group consisting of irinotecan, 5-fluorouracil, taxol, cisplatin, doxorubicin, oxaliplatin, and cyclophasphamide.

### Claim 7

A method for identifying tumors likely to respond to chemotherapy comprising the steps of:
a) administering a selenium compound selected from the group consisting of methylselenocysteine (MSC) and seleno-L-methionine (SLM);
b) monitoring an indicator of microvessel maturation in the tumor over a period of between 3-8 days after administration of the selenium compound;
wherein an increase in the microvessel density of the tumor in response to selenium compound administration is indicative of the tumor being responsive to the subsequent chemotherapeutic agent.

### Claim 8 (depends on 7)

The method of claim 7, wherein blood vessel maturation is monitored by magnetic resonance imaging.

### Claim 9 (depends on 7)

The method of claim 7, wherein the blood vessel maturation is monitored by immunohistochemical techniques on a biopsy sample of the tumor.

### Claim 10 (depends on 7)

The method of claim 7, wherein the MSC or SLM is administered for 3 days before carrying out step b.

### Claim 11 (depends on 7)

The method of claim 7, wherein the MSC or SLM is administered for 5 days before carrying out step b.