Sigma-2 receptor radiotracers for imaging the proliferative status of solid tumors

A method of determining the proliferative status of cells comprised by a mammalian tumor in vivo, the method comprising:

• a) administering to a mammal comprising a tumor, 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 C1-C4 alkoxyl, a C1-C4 alkyl, a C1-C4 fluoroalkyl, a C1-C4 fluoroalkoxyl, a CF3, and an OCF3, 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 A1 is independently selected from the group consisting of a C1-C4 alkoxyl, a C1-C4 fluoroalkyl and a C1-C4 fluoroalkoxyl;
• and
• b) determining, for cells comprised by the tumor, a ratio of proliferating cells to quiescent cells.

A method of determining progression of a cancerous tumor in a mammal, the method comprising:

• a) administering to a mammal 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 C1-C4 alkoxyl, a C1-C4 alkyl, a C1-C4 fluoroalkyl, a C1-C4 fluoroalkoxyl, a CF3, and an OCF3, 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 A1 is independently selected from the group consisting of a C1-C4 alkoxyl, a C1-C4 fluoroalkyl and a C1-C4 fluoroalkoxyl;
• and
• b) acquiring, at a first selected time, a first image of the distribution of the radioisotope in the mammal;
• c) acquiring, at a second selected time, a second image of the distribution of the radioisotope in the mammal,
• whereby the radioisotope accumulates at a tumor, and a change in intensity of the radioisotope at the tumor from the first selected time to the second selected time indicates a change in tumor size.