Detection of cancer cells in vitro using sigma-2 receptor ligands as radiotracers
Methods for detection of cancer cells and for determining the proliferative status of cells in a tissue sample in vitro are disclosed. These methods comprise contacting a tissue sample with a radiolabeled compound or salt thereof of Formula wherein at least one of X, Y, and Z comprises a radioisotope, n is an integer from 2 to about 10; and each of A and A 1 is a C 1 -C 4 alkoxyl, a C 1 -C 4 fluoroalkyl or a C 1 -C 4 fluoroalkoxyl. The methods further comprise detecting the distribution of the radioisotope in the tissue sample, whereby a cell having a high density of the radioisotope compared to quiescent cells is diagnostic for a cancer cell.
1. A method for detecting a cancer cell in a mammalian tissue sample in vitro, the method comprising:
a) contacting a mammalian tissue sample with a radiolabeled compound or salt thereof of Formula
wherein:
each of X, Y, and Z is a substituent selected from the group consisting of a hydrogen, a halogen, a C 1 -C 4 alkoxyl, a C 1 -C 4 alkyl, a C 1 -C 4 fluoroalkyl, a C 1 -C 4 fluoroalkoxyl, a CF 3 , and an OCF 3 , wherein at least one of X, Y and Z comprises a radioisotope selected from the group consisting of a bromine, an iodine, a carbon of a 2-methoxyl and a tritium of a 2-methoxyl;
n is an integer from 2 to about 10; and
each of A and A 1 is independently selected from the group consisting of a C 1 -C 4 alkoxyl, a C 1 -C 4 fluoroalkyl and a C 1 -C 4 fluoroalkoxyl; and
b) detecting the distribution of the radioisotope in the tissue sample, whereby a cell having a high density of the radioisotope compared to quiescent cells is diagnostic for a cancer cell.
2. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the radioisotope is selected from the group consisting of an 3 H and a 11 C.
3. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the compound is selected from the group consisting of:
4. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein each of A and A 1 is a methoxyl.
5. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the compound is Compound 6
and wherein the Br is a 76 Br.
6. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the compound is Compound 10
and wherein the 2-methoxyl comprises a 11 C.
7. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the radioisotope is selected from the group consisting of an 123 I, an 124 I and an 125 I.
8. A method for detecting a cancer cell in vitro in accordance with claim 7 , wherein the radioisotope is selected from the group consisting of an 123 I and an 125 I.
9. A method for detecting a cancer cell in vitro in accordance with claim 7 , wherein the compound has the structure
wherein X is H or OCH 3 and n=2 or 4.
10. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the mammalian tissue sample is a human tissue sample.
11. A method for detecting a cancer cell in vitro in accordance with claim 1 , wherein the detecting the distribution of the radioisotope comprises imaging the distribution of the radioisotope.
12. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro, the method comprising:
a) contacting a mammalian tissue sample in vitro with a radiolabeled compound or salt thereof of Formula
wherein:
each of X, Y, and Z is a substituent selected from the group consisting of a hydrogen, a halogen, a C 1 -C 4 alkoxyl, a C 1 -C 4 alkyl, a C 1 -C 4 fluoroalkyl, a C 1 -C 4 fluoroalkoxyl, a CF 3 , and an OCF 3 , wherein at least one of X, Y and Z comprises a radioisotope selected from the group consisting of a bromine, an iodine, a carbon of a 2-methoxyl and a tritium of a 2-methoxyl;
n is an integer from 2 to about 10;
each of A and A 1 is independently selected from the group consisting of a C 1 -C 4 alkoxyl, a C 1 -C 4 fluoroalkyl and a C 1 -C 4 fluoroalkoxyl; and
b) determining, for cells comprised by the sample, a ratio of proliferating cells to quiescent cells.
13. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the radioisotope is selected from the group consisting of a 3 H and a 11 C.
14. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the compound is selected from the group consisting of:
15. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein each of A and A 1 is a methoxyl.
16. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the compound is Compound 6
and wherein the Br is a 76 Br.
17. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the compound is Compound 10
and wherein the 2-methoxyl comprises a 11 C.
18. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the compound has the structure
wherein X is H or OCH 3 and n=2 or 4, and the I is selected from the group consisting of an 123 I, an 124 I and an 125 I.
19. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the mammal is a human.
20. A method of determining the proliferative status of cells comprised by a mammalian tissue sample in vitro in accordance with claim 12 , wherein the determining a ratio of proliferating cells to quiescent cells comprises imaging the distribution of the radioisotope.