PET-imaging immunomodulators
The invention relates to the synthesis and use of 18 F-labeled millamolecules for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.
1. A compound of formula (I)
or a pharmaceutically acceptable salt thereof, wherein x is an integer from 1 to 8 and R is a C 1 -C 6 alkyl group.
2. A compound of claim 1 of formula (II)
or a pharmaceutically acceptable salt thereof, wherein x is an integer from 1 to 8 and R is hydrogen or a C 1 -C 6 alkyl group.
3. A compound of claim 1 of formula (III)
or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
5. A method of obtaining an image of a compound of claim 1 , the method comprising,
a) administering the compound to a subject; and
b) imaging in vivo the distribution of the compound positron emission tomography (PET) scanning.
6. The method of claim 5 , wherein the imaged distribution of the compound is indicative of the presence or absence of a disease.
7. A method of monitoring the progress of a disease in a subject, the method comprising
(a) administering to a subject in need thereof a compound of claim 1 which binds to a target molecule associated with the presence of the disease at a first time point and obtaining an image of at least a portion of the subject to determine an amount of diseased cells or tissue; and
(b) administering to the subject a compound of claim 1 at one or more subsequent time points and obtaining an image of at least a portion of the subject at each time point; wherein the dimension and location of diseased cells or tissue at each time point is indicative of the progress of the disease.
8. The method of claim 7 wherein the disease is selected from the group consisting of solid cancers, hematopoietic cancers, hematological cancers, autoimmune disease, neurodegenerative disease cardiovascular disease, and pathogenic infection.
9. A method of quantifying diseased cells or tissues in a subject, the method comprising
(a) administering to a subject having diseased cells or tissues a compound of claim 1 which binds to a target molecule located with the diseased cells or tissues; and
(b) detecting radioactive emissions of the compound of claim 1 in the diseased cells or tissue, wherein the level and distribution of the radioactive emissions in the diseased cells or tissues is a quantitative measure of the diseased cells or tissues.
10. A method of obtaining a quantitative image of tissues or cells expressing PD-L1, the method comprising contacting the tissues or cells with a compound of claim 1 which binds to PD-L1, and detecting or quantifying the tissues or cells expressing PD-L1 using positron emission tomography (PET).
11. A method of screening for an agent that binds to PD-L1 comprising the steps of
(a) contacting cells expressing PD-L1 with a compound of claim 1 which binds to PD-L1 in the presence and absence of a candidate agent; and
(b) imaging the cells in the presence and absence of the candidate agent using positron emission tomography (PET),
wherein a decrease in the amount of radioactive emissions in the presence of the candidate agent is indicative that the candidate agent binds to PD-L1.