Hsp90-targeted inflammation and infection imaging and therapy

A method of imaging a tissue affected by an inflammation and/or infection in a subject in need thereof, comprising steps of:

• (a) administering to the subject a labeled compound of any of formula I to IX as described in the specification;
• and
• (b) imaging the tissue by detecting the labeled compound in the subject.

The method of any one of the preceding claims, further comprising detecting the presence of the inflammation and/or infection in the tissue by analyzing an image obtained in step (b).

The method of any one of the preceding claims, wherein the labeled compound is labeled through substituting at least one hydrogen atom in the compound with at least one group that produces higher signal intensity than the at least one hydrogen atom.

The method of any one of the preceding claims, wherein at least one atom in the labeled compound is enriched in an isotope that can be detected by a medical imaging technique.

The method of any one of the preceding claims, wherein the labeled compound binds to one or more isoforms of Hsp90.

The method of any one of the preceding claims, wherein the labeled compound binds to a stress-specific form of Hsp90.

The method of any one of the preceding claims, wherein the labeled compound binds to a stress-specific form of Hsp90 selectively over a housekeeping form of Hsp90.

The method of any one of the preceding claims, wherein the labeled compound has a KD of less than about 1 mM, about 100 μM, about 10 μM, or about 1 μM.

The method of any one of the preceding claims, wherein the labeled compound inhibits Hsp90.

The method of any one of the preceding claims, wherein the imaging process comprises tomography.

The method of any one of the preceding claims, further comprising collecting electrocardiography (ECG) data.

The method of any one of the preceding claims, wherein the step of imaging comprises imaging by multiple modalities.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the lung of the subject.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the colon of the subject.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the skin of the subject.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the macrophages of the subject.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the stroma of the subject.

The method of any one of the preceding claims, wherein detecting the labeled compound in the subject comprises measuring signal intensity from the cardiac tissue of the subject.

The method of any one of the preceding claims, wherein the inflammation and/or infection is associated with Hsp90.

The method of any one of the preceding claims, wherein the inflammation and/or infection is associated with stress-specific Hsp90.

The method of any one of the preceding claims, wherein the labeled compound is administered before, during, or after administration of a non-radioactive therapeutic compound.

The method of any one of the preceding claims, wherein the labeled compound has a physical half-life of at least about 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 18, 24, 36, 48, 72, 96, or 100.3 hours.

The method of any one of the preceding claims, wherein the imaging measures the accessibility of Hsp90 in the tissue affected by the inflammation and/or infection to a therapeutic compound.

The method of any one of the preceding claims, wherein the imaging measures the concentrations of a labeled and/or non-labeled therapeutic compound in the tissue affected by the inflammation and/or infection.

The method of any one of the preceding claims, wherein the imaging measures the occupancy or saturation of Hsp90 by a therapeutic compound in the tissue affected by the inflammation and/or infection, or the ability of a therapeutic compound to displace the labeled compound in the tissue affected by the inflammation and/or infection.

A method for the treatment of a tissue affected by, or prevention of an tissue from, an inflammation and/or infection, comprising steps of

• (a) administering a labeled compound of any of formula I to IX to a subject in need thereof, and
• (b) imaging the tissue by detecting the labeled compound in the subject.

A method for the treatment of a tissue affected by, or prevention of an tissue from, an inflammation and/or infection, comprising the step of administering a labeled compound of any of formula I to IX to a subject in need thereof.

A method for the treatment of a tissue affected by, or prevention of an tissue from, an inflammation and/or infection, comprising the step of administering a non-radioactive therapeutic compound of formula X.

The method of any one of the preceding claims, wherein the labeled compound is a labeled compound having the structure of:

• wherein Y′ is —CH2— or S;
• X4 is hydrogen or halogen;
• and R is an amino alkyl moiety, optionally substituted on the amino nitrogen with one or two carbon-containing substituents selected independently from the group consisting of alkyl, alkenyl and alkynyl substituents, wherein the total number of carbons in the amino alkyl moiety is from 1 to 9.

The method of any one of the preceding claims, wherein the labeled compound is labeled compound A:

The method of any one of the preceding claims, wherein the labeled compound is radiolabelled.

The method of any one of the preceding claims, wherein the labeled compound comprises an isotope which decays by positron emission.

The method of any one of the preceding claims, wherein the labeled compound comprises an isotope selected from 124I, 11C, 15O, 13N, and 18F.

The method of any one of the preceding claims, wherein the labeled compound comprises 124I.

The method of any one of the preceding claims, wherein the labeled compound comprises an isotope that decays by electron capture.

The method of any one of the preceding claims, wherein the labeled compound comprises an isotope selected from 123I and 131I.

The method of any one of the preceding claims, wherein the labeled compound comprises one or more 19F.

The method of any one of the preceding claims, wherein the labeled compound comprises a nanotube containing contrast reagents for MRI.

The method of any of the preceding claims, wherein the imaging is non-invasive.

The method of any one of the preceding claims, further comprising identifying abnormal signal compared to a reference, wherein the abnormal signal indicates an inflammation and/or infection in the tissue.

The method of any one of the preceding claims, further comprising identifying decreased signal compared to a reference, wherein the decreased signal indicates amelioration of an inflammation and/or infection in the tissue.

The method of any one of the preceding claims, wherein the subject is a cancer patient.