Compositions for imaging pain and stress in vivo

Abstract

Briefly described, embodiments of the present disclosure relate to methods and compositions for imaging pain and/or stress in a subject and methods and compositions for treating associated conditions. In particular, the present disclosure relates to the use of labeled compounds to provide objective diagnosis of pain and/or stress, for imaging regions associated with pain and/or stress, and for treating pain in a subject.

1 - 57 . (canceled) 
     
     
         58 . A method of imaging stress in a subject in vivo comprising:
 administering to the subject an imaging composition comprising a labeled annexin including annexin coupled to a biocompatible radionuclide; and   measuring radiation emission from the radionuclide in at least a portion of the central nervous system of the subject to construct an image of radiation emission, wherein the image is a representation of stress in the subject.   
     
     
         59 . The method of  claim 58 , wherein the radionuclide is selected from the group consisting of Iodine 123, Iodine 131, Gallium 67, Indium 111, Fluorine 18, and Technetium 99 m (Tc99m). 
     
     
         60 . The method of  claim 59 , wherein the radionuclide is Tc99m to form Tc99m-labeled annexin. 
     
     
         61 . The method of  claim 60 , wherein the Tc99m is linked to the annexin via hydrazino nicotinamide (HYNIC) or via the internal radionuclide chelating site of annexin V-128. 
     
     
         62 . The method of  claim 60 , wherein the Tc99m is linked to the annexin via the internal radionuclide chelating site of annexin V-128. 
     
     
         63 . The method of  claim 60 , wherein the amount of Tc99m-labeled annexin administered results in a dose of up to about 20 mCi. 
     
     
         64 . The method of  claim 60 , wherein the amount of Tc99m-labeled annexin administered results in a dose of about 5 to 20 mCi. 
     
     
         65 . The method of  claim 58 , wherein the radiation is measured with a radiation detector device and wherein the radiation detection device is a gamma ray detector device and the radiation emission is gamma ray emission. 
     
     
         66 . The method of  claim 65 , where the gamma ray detector device is a gamma scintillation camera. 
     
     
         67 . The method of  claim 65 , wherein the measuring of gamma ray emission to construct the image is done about 5 minutes to 2 hours after administration of the labeled annexin. 
     
     
         68 . The method of  claim 65 , wherein the measuring of gamma ray emission to construct the image is done about 1 hour after administration of the labeled annexin. 
     
     
         69 . The method of  claim 58 , further comprising repeating the step of measuring radiation emission at selected intervals, wherein said repeating is effective to track changes in the intensity of radiation emission from the subject over time, reflecting changes in the intensity of the stress. 
     
     
         70 . The method of  claim 58 , further comprising repeating the step of measuring radiation emission at selected intervals, wherein said repeating is effective to track changes in the localization of radiation emission in the subject over time, reflecting changes in the location of cells reacting to stress stimulus. 
     
     
         71 . The method of  claim 58 , wherein the annexin is annexin V. 
     
     
         72 . The method of  claim 58 , wherein the annexin is annexin V-128. 
     
     
         73 . The method of  claim 58 , wherein the amount of labeled annexin administered is less than about 300 μg protein/kg. 
     
     
         74 . The method of  claim 58 , wherein the amount of labeled annexin administered is about 1 to 10 μg protein/kg. 
     
     
         75 . The method of  claim 58 , wherein the labeled annexin is administered via a route of administration selected from at least one of the following: intravenously, intraperitoneally, intrathecally, intrapleurally, intralymphatically, and intramuscularly. 
     
     
         76 . The method of  claim 58 , wherein the radiation emission is measured from the head of the subject or a portion thereof. 
     
     
         77 . The method of  claim 58 , wherein radiation emission is measured from the spine of the subject or a portion thereof. 
     
     
         78 . The method of  claim 58 , wherein the radiation is measured with a radiation detector device and wherein the radiation detection device is a positron emission detector device. 
     
     
         79 . A method of imaging stress in a subject in vivo comprising:
 administering to the subject an imaging composition comprising a labeled annexin including annexin coupled to a contrast agent; and   obtaining a magnetic resonance image of at least a portion of the central nervous system of the subject, wherein said image is a representation of stress in said subject.   
     
     
         80 . The method of  claim 79 , wherein the contrast agent is selected from at least one of the following: a paramagnetic agent, a gadolinium-chelating group complex, a gadolinium-diethylenetriamine penta-acetic acid, a superparamagnetic agent, a metal oxide, an iron oxide, a polymer coated metal oxide, and a dextran coated iron oxide. 
     
     
         81 . The method of  claim 79 , wherein the annexin is annexin V. 
     
     
         82 . The method of  claim 79 , wherein the annexin is annexin V-128. 
     
     
         83 . The method of  claim 79 , wherein the magnetic resonance image is obtained about 5 minutes to 2 hours after the administration of the magnetic resonance imaging composition. 
     
     
         84 . The method of  claim 79 , wherein the magnetic resonance image is obtained about 12 to 30 hours after the administration of the magnetic resonance imaging composition. 
     
     
         85 . The method of  claim 79 , further comprising obtaining a magnetic resonance image at a plurality of time points, thereby monitoring changes in the number of cells responding to stress. 
     
     
         86 . The method of  claim 79 , further comprising obtaining a magnetic resonance image at a plurality of time points, thereby monitoring changes in the location of cells responding to stress. 
     
     
         87 . The method of  claim 79 , wherein the magnetic resonance imaging composition is administered at a concentration of about 1 to 500 μg protein/kg. 
     
     
         88 . The method of  claim 79 , wherein the magnetic resonance imaging composition is administered at a concentration of less than about 300 μg protein/kg.