PSMA—targeted NIR dyes and their uses
The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.
1. A compound selected from the group consisting of:
2. A compound selected from the group consisting of:
3. The compound of claim 1 wherein the compound has an absorption and emission maxima between about 500 nm and about 900 nm.
4. The compound of claim 2 wherein the compound has an absorption and emission maxima between about 500 nm and about 900 nm.
5. The compound of claim 1 wherein the compound is made to fluoresce after distribution thereof in tissue cells.
6. The compound of claim 2 wherein the compound is made to fluoresce after distribution thereof in tissue cells.
7. A method of optical imaging of a biological tissue that expresses PSMA, the method comprising:
(a) contacting the biological tissue with a composition of claim 1 ,
(b) allowing time for the compound in the composition to distribute within a biological target;
(c) illuminating the biological tissue with an excitation light of a wavelength absorbable by the compound; and
(d) detecting an optical signal emitted by the compound.
8. The method of claim 7 , wherein the optical signal emitted by the compound is used to construct an image.
9. The method of claim 7 , wherein the biological tissue is selected from the group consisting of prostate cells, prostate cancer cells, bladder cancer cells, pancreatic cancer cells, liver cancer cells, lung cancer cells, kidney cancer cells, sarcoma cells, breast cancer cells, brain cancer cells, neuroendocrine carcinoma cells, colon cancer cells, testicular cancer cells and melanoma cells.
10. A method of optical imaging of a biological tissue that expresses PSMA, the method comprising:
(a) contacting the biological tissue with a composition of claim 2 ,
(b) allowing time for the compound in the composition to distribute within a biological target;
(c) illuminating the biological tissue with an excitation light of a wavelength absorbable by the compound; and
(d) detecting an optical signal emitted by the compound.
11. The method of claim 10 , wherein the optical signal emitted by the compound is used to construct an image.
12. The method of claim 10 , wherein the biological tissue is selected from the group consisting of prostate cells, prostate cancer cells, bladder cancer cells, pancreatic cancer cells, liver cancer cells, lung cancer cells, kidney cancer cells, sarcoma cells, breast cancer cells, brain cancer cells, neuroendocrine carcinoma cells, colon cancer cells, testicular cancer cells and melanoma cells.
13. A method of identifying a target cell type in a biological sample comprising
a. contacting the biological sample with a compound of claim 1 for a time and under conditions that allow for binding of the compound to at least one cell of the target cell type; and
b. optically detecting presence or absence of the compound of in the biological sample,
c. wherein presence of the compound in detecting step b. indicates that the target cell type is present in the biological sample.
14. A method of identifying a target cell type in a biological sample comprising
a. contacting the biological sample with a compound of claim 2 for a time and under conditions that allow for binding of the compound to at least one cell of the target cell type; and
b. optically detecting presence or absence of the compound of in the biological sample,
c. wherein presence of the compound in detecting step b) indicates that the target cell type is present in the biological sample.
15. The method of claim 7 , wherein the optical signal is detected using an endoscope, catheter, tomographic system, hand-held optical imaging system, surgical goggles, or intra-operative microscope.
16. The method of claim 10 , wherein the optical signal is detected using an endoscope, catheter, tomographic system, hand-held optical imaging system, surgical goggles, or intra-operative microscope.