Ether and alkyl phospholipid compounds for treating cancer and imaging and detection of cancer stem cells

a technology of alkyl phospholipids and stem cells, applied in the direction of drug compositions, sexual disorders, therapy, etc., can solve the problems of long-term ineffectiveness of chemotherapy agents against cancer stem cells, and ineffective current cancer chemotherapeutic agents which can successfully kill differentiated tumor cells

Inactive Publication Date: 2010-12-16
CELLECTAR
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In one aspect, this invention relates to a method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a radiolabeled ether or alkyl phospholipid compound of Formula I

Problems solved by technology

Furthermore, it has also been widely reported that current cancer chemotherapeutic agents which can successfully kill differentiated tumor cells are actually ineffective against the small population of cancer stem cells which may be a contributing factor to the regeneration of cancer cells after chemotherapy.
Several studies have suggested that long-term ineffectiveness of chemotherapy agents against cancer stem cells may be due to their lack of penetration into these cells.

Method used

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  • Ether and alkyl phospholipid compounds for treating cancer and imaging and detection of cancer stem cells
  • Ether and alkyl phospholipid compounds for treating cancer and imaging and detection of cancer stem cells
  • Ether and alkyl phospholipid compounds for treating cancer and imaging and detection of cancer stem cells

Examples

Experimental program
Comparison scheme
Effect test

example 1

Testing CLR1501 In Vitro to Determine if the Compound Enters Cancer Stem Cells

[0087]An objective of this experiment is to determine whether an alkyl phospholipid compound CLR1501 (a fluorescent version of CLR1404) enters cancer stem cells in culture utilizing confocal microscopy.

[0088]CLR1501 has the following structure:

[0089]We have shown in cell culture studies that CLR1501 is preferentially taken up by a variety of tumor cells relative to their normal host tissue cells. The agent initially associates with outer cell membranes, becomes internalized, and then associates with other subcellular organelles and membranes. It does not appear to enter the nucleus even after 24 hours.

[0090]A similar experiment utilizing CLR1501 could be performed to demonstrate that alkyl phospholipid compounds can penetrate cancer stem cells. A comparison in brain tumors, for example, would consist of doing a parallel comparison of CLR1501 uptake in cultured glial cells (normal brain neuronal cells), nor...

example 2

Testing CLR1404 In Vivo to Determine if the Compound Enters Cancer Stem Cells

[0092]An objective of this experiment is to determine whether 124I-CLR1404 enters cancer stem cells in vivo utilizing microPET / CT / MRI scanning.

[0093]Utilizing microPET / CT hybrid scanning of our tumor-bearing mouse models, we can quantitatively monitor tumor uptake and retention three-dimensionally in intact rodent tumor models, including xenografts of human tumors in immune-compromised mice, as well as spontaneous mouse and rat tumor models.

[0094]To evaluate the potential uptake of CLR1404 into cancer stem cells, using glioma as an example, we would perform in vivo microPET / CT / MRI hybrid scanning of anesthetized animals bearing orthotopic brain tumors derived from human glioma stem cells. Isolation of these cells would be similar to that described in Example 1, with the exception that the tumor stem cells would be implanted orthotopically into the mouse brain. A comparison would also be done with normal gli...

example 3

Testing CLR1404 In Vivo to Determine if the Compound Reduces the Number of Cancer Stem Cells

[0095]An objective of this experiment is to determine whether 125I- or 131I-CLR1404 can kill cancer stem cells and compare survival of normally differentiated glioma cells.

[0096]The same glioma model as proposed for the experiments in Examples 1 and 2 may be utilized. It would be desirable to compare the therapeutic efficacy of both 125I-CLR1404 and 131I-CLR1404. Accordingly, cohorts of brain tumor bearing mice would consist of sham operated (n=3), normally differentiated glioma (n=3), and stem cell derived glioma (n=6). Tumor would initially be confirmed noninvasively with high field MRI imaging prior to administration of the agent. Animals would receive a mixture of imaging (124I) and therapeutic (125I or 131I) agent at T0 and scanned up to 4 days post injection to determine suitable tumor targeting. After a predetermined period of time, animals will be euthanized, tumors excised, cells dig...

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Abstract

Methods and compositions utilizing ether and alkyl phospholipid ether analog compounds for treating cancer and imaging, monitoring, and detecting cancer stem cells in humans.

Description

BACKGROUND OF THE INVENTION[0001]Stem cells, which possess the unique ability to undergo self-renewal and differentiation into tissue-specific cells, give rise to all tissues in the body. Unlike embryonic stem cells which can differentiate into many different cell types, tissue specific stem cells can only form cells unique to one tissue. Recent advances in stem cell molecular biology techniques have enabled researchers to examine the concept that a malignant tumor can be formed and maintained due to the presence of a small number of cancer-specific stem cells.[0002]Stem cells can renew themselves. This self-renewal process of all stem cells, including tumor stem cells, is known to be very tightly regulated. Many reports in the past several years have confirmed that small populations of cancer stem cells have been found in a variety of cancers including glioma, breast, pancreas, ovarian, hepatocellular carcinoma, and melanoma, to name a few. Furthermore, it has also been widely repo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K51/00C12Q1/02A61P35/04
CPCA61K51/0489A61K45/06A61K31/661C07B59/00A61K51/0408A61P1/00A61P1/18A61P11/00A61P13/08A61P13/12A61P15/00A61P17/00A61P25/00A61P35/00A61P35/04A61P43/00
Inventor WEICHERT, JAMEY P.PINCHUK, ANATOLYKANDELA, IRAWATILONGINO, MARCCLARKE, WILLIAM R.
Owner CELLECTAR
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