Luminescent phospholipid analogs for the identification and isolation of circulating tumor cells
The present invention is directed to a method of identifying, isolating, and enabling downstream analysis of circulating tumor cells comprising contacting a blood or blood serum sample of a subject with a composition comprising a phospholipid ether analog bound to a luminescent molecule or a magnetic bead and subjecting the blood or blood serum sample of the subject to fluorescent microscopy, flow cytometry or magnetic isolation.
1. A method of isolating tumor cells comprising the steps of:
(i) contacting a blood or blood serum sample from a subject having one or more circulating tumor cells (CTCs) with a compound of formula (I),
wherein:
n is an integer from 16 to 30;
Y is selected from the group consisting of —H, —OH, —OR, —C(O)OH, and —OC(O)R, wherein R is an alkyl; and
X is a luminescent molecule;
(ii) subjecting the blood or blood serum sample to flow cytometry; and
(iii) isolating the one or more CTCs following (ii),
wherein the one or more CTCs are selected from the group consisting of a breast cancer cell, a lung cancer cell, a thyroid cancer cell, a cervical cancer cell, a squamous cell, a carcinoma cell, a prostate cancer cell, a pancreas cancer, a colorectal cancer cell, and a cancer stem cell.
2. The method of claim 1 , wherein the luminescent molecule is a fluorophore.
3. The method of claim 2 wherein the fluorophore is selected from the group consisting of
wherein each R of the fluorophore is independently H, CH 3 , C 2 H 5 , or C 3 H 7 .
4. The method of claim 3 wherein the compound is a compound of formula (II) and the fluorophore is selected from the group consisting of
5. The method of claim 1 , wherein the flow cytometry comprises fluorescence activated cell sorting.
6. The method of claim 1 , further comprising utilizing the one or more isolated CTCs in a technology selected from the group consisting of protein isolation, RNA isolation, DNA isolation, gene translocation analysis, gene amplification analysis, and fluorescent in-situ hybridization.
7. The method of claim 1 , wherein the one or more circulating tumor cells are prostate cancer cells.
8. The method of claim 7 , wherein the compound is a compound of formula (V),
or a compound of formula (VI),