# US 2014/0154178 A1 · Methods of detecting myelin basic protein > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154178 A1 - Document ID: US20140154178A1 - Status: Published application - Kind: A1 - Application number: 13/689,819 - Filed: 2012-11-30 - Published: 2014-06-05 - Earliest claimed: 2012-11-30 - Assignees: General Electric Company - Applicants: General Electric Company - Inventors: Tiberiu Mircea Siclovan; Cristina Abucay Tan Hehir; Rong Zhang; Victoria Eugenia Cotero; Anshika Bajaj - Web page: https://patentgrep.com/patent/US20140154178A1 ## CPC - A61K 49/0021: {the fluorescent group being a small organic molecule} - A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 2800/285: Demyelinating diseases; Multipel sclerosis - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract A method and a kit for detecting myelin basic protein are provided. The method comprises administering an agent, which binds to myelin basic protein (MBP), to a subject at risk of or diagnosed with a myelin-associated neuropathy, and determining myelination by detecting the agent resided in the subject. The amount of the agent present in the subject is indicative of a myelin-associated neuropathy. A method of quantifying an amount of MBP present in a tissue sample is also provided, wherein the method comprises contacting the tissue sample with the same agent, detecting the agent present in the tissue sample; and quantifying an amount of the agent present in the tissue sample. ## Claims ### Claim 1 A method of detecting myelin-associated neuropathy, comprising: administering an agent to a subject at risk of or diagnosed with a myelin-associated neuropathy, wherein said agent; binds to myelin basic protein (MBP); and comprises a compound of Formula I, a 13C enriched compound of Formula I, a 19F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof; wherein R1 and R2 are independently at each occurrence a hydrogen, hydroxyl group, C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, or C2-C30 aromatic radicals with the proviso that R1 and R2 are not both equal to a hydroxyl group; R3 is hydrogen, a hydroxyl group, an alkoxy group, a C1-C6 hydroxyalkyl group, a C1-C6 alkyl group or a substituted alkyl group; and the summation of alkyl groups of R1, R2 and R3 is less than or equal to 16 carbon atoms; and determining myelination by detecting the agent resided in the subject, and whereby the amount of the agent present in the subject is indicative of a myelin-associated neuropathy. ### Claim 2 (depends on 1) The method of claim 1, wherein R3 is hydrogen, an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group. ### Claim 3 (depends on 1) The method of claim 1, wherein at least one of the R1 and R2 is hydrogen, C1-C30 aliphatic radicals, or C2-C30 aromatic radicals. ### Claim 4 (depends on 1) The method of claim 1, wherein the R1 is hydrogen and R2 is a 4-aminobenzyl group. ### Claim 5 (depends on 1) The method of claim 1, wherein R1 is hydrogen and R2 is a hydroxyethyl group. ### Claim 6 (depends on 1) The method of claim 1, wherein R1 and R2 are hydroxyethyl groups. ### Claim 7 (depends on 1) The method of claim 1, wherein both R1 and R2 are hydrogen. ### Claim 8 (depends on 1) The method of claim 1, wherein the agent crosses the blood brain barrier (BBB). ### Claim 9 (depends on 1) The method of claim 1, wherein the agent crosses the blood nerve barrier (BNB). ### Claim 10 (depends on 1) The method of claim 1, wherein a molecular weight of the compound of Formula I is less than or equal to 500 Da. ### Claim 11 (depends on 1) The method of claim 1, wherein a LogP value of the compound of Formula I is less than or equal to 5. ### Claim 12 (depends on 1) The method of claim 1, wherein the compound of Formula I is ### Claim 13 (depends on 1) The method of claim 1, wherein the compound of Formula I is ### Claim 14 (depends on 1) The method of claim 1, wherein the compound of Formula I is ### Claim 15 (depends on 1) The method of claim 1, wherein the compound of Formula I is ### Claim 16 (depends on 1) The method of claim 1, wherein the compound of Formula I is ### Claim 17 (depends on 1) The method of claim 1, wherein the compound of Formula I is wherein R1 is a hydrogen, a hydroxyl group, alkyl group, hydroxyalkyl group, alkoxy group, a C2-C30 aromatic radical; and n is an integer between 0 and 4. ### Claim 18 (depends on 1) The method of claim 1, wherein the compound of Formula I is and wherein m and n are integers such that m+n is less than or equal to 4. ### Claim 19 (depends on 1) The method of claim 1, wherein the administration comprises intravenous injection, intraperitoneal injection, subcutaneous injection, intramuscular injection, intrathecal injection, intracerebral injection, intracerebroventricular injection, intraspinal injection, or combinations thereof. ### Claim 20 (depends on 1) The method of claim 1, wherein the detection is effected by gamma imaging, fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, magnetic resonance imaging, magnetic resonance spectroscopy, or combinations thereof. ### Claim 21 (depends on 1) The method of claim 1, wherein the detection is effected by: applying a light source on the subject, wherein the light source is tuned to the spectral excitation characteristics of the compound of Formula I; and observing the subject through an optical filter tuned to the spectral emission characteristics of the compound of Formula I. ### Claim 22 (depends on 1) The method of claim 1, further comprising quantifying an amount of the agent resided in the subject. ### Claim 23 (depends on 22) The method of claim 22 wherein the quantifying step comprises comparing the myelination in the subject with a control sample administered with the same agent, ### Claim 24 (depends on 22) The method of claim 22, wherein the quantifying step comprises measuring a radioactivity of the agent present in the subject and wherein the agent comprises the radioactive derivative of Formula I. ### Claim 25 (depends on 1) The method of claim 1, wherein the myelin-associated disease comprises multiple sclerosis, Alzheimer's disease, Guillain-Barré syndrome, leukodystrophies metachromatic leukodystrophy, Refsum's disease, adrenoleukodystrophy, Krabbe's disease, phenylketonuria, Canavan disease, Pelizaeus-Merzbacher disease, Alexander's disease, diabetic neuropathy, chemotherapy-induced neuropathy, or a combination thereof. ### Claim 26 A method of imaging nerves in a surgical field, comprising: contacting a surgical site of a subject with an agent which binds to myelin basic protein (MBP) and wherein said agent comprises; a compound of Formula I, a 13C enriched compound of Formula I, a 19F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof; wherein R1 and R2 are independently at each occurrence a hydrogen, hydroxyl group, C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, or C2-C30 aromatic radicals with the proviso that R1 and R2 are not both equal to a hydroxyl group; R3 is hydrogen, a hydroxyl group, an alkoxy group, a C1-C6 hydroxyalkyl group, a C1-C6 alkyl group or a substituted alkyl group; and the summation of alkyl groups of R1, R2 and R3 is less than or equal to 16 carbon atoms; and detecting the agent. ### Claim 27 (depends on 26) The method of claim 26, wherein at least one of the R1 and R2 is hydrogen, C1-C30 aliphatic radicals, or C2-C30 aromatic radicals. ### Claim 28 (depends on 1, 26) The method of claim 26, The method of claim 1, wherein R3 is hydrogen an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group. ### Claim 29 (depends on 26) The method of claim 26, wherein the agent is formulated in a buffer comprising cyclodextrin in a range between 5-35%. ### Claim 30 (depends on 26) The method of claim 26, wherein the detection comprises: applying a light source on the surgical site of the subject, wherein the light source is tuned to the spectral excitation characteristics of the compound of Formula I; and observing the surgical site of the subject through an optical filter tuned to the spectral emission characteristics of the compound of Formula I. ### Claim 31 A method of quantifying an amount of myelin basic protein (MBP) present in a tissue sample, comprising: contacting the tissue sample with an agent wherein said agent comprises; a compound of Formula I, a 13C enriched compound of Formula I, a 19F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof; wherein R1 and R2 are independently at each occurrence a hydrogen, a hydroxyl group, C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, or C2-C30 aromatic radicals with the proviso that R1 and R2 are not both equal to a hydroxyl group; R3 is hydrogen, a hydroxyl group, an alkoxy group, a C1-C6 hydroxyalkyl group, a C1-C6 alkyl group or a substituted alkyl group; and the summation of alkyl groups of R1, R2 and R3 is less than or equal to 16 carbon atoms; detecting the agent present in the tissue sample; and quantifying an amount of the agent present in the tissue sample. ### Claim 32 (depends on 31) The method of claim 31, wherein at least one of the R1 and R2 is hydrogen, C1-C30 aliphatic radicals, or C2-C30 aromatic radicals. ### Claim 33 (depends on 31) The method of claim 31, wherein R3 is hydrogen, an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group. ### Claim 34 (depends on 31) The method of claim 31, wherein the detecting is effected by gamma imaging, fluorescence microscopy, laser-confocal microscopy, cross-polarization microscopy, autoradiography, magnetic resonance imaging, magnetic resonance spectroscopy, or combination thereof. ### Claim 35 (depends on 31) The method of claim 31, wherein the quantifying step comprises comparing the myelination in the tissue sample with a control sample administered with the same agent. ### Claim 36 A kit for detecting myelin-associated neuropathy in a subject, comprising: an agent wherein said agent binds to myelin basic protein (MBP) and comprises; a compound of Formula I, a 13C enriched compound of Formula I, a 19F-labeled derivative of Formula I, or a radioisotope derivative of Formula I or combinations thereof; wherein R1 and R2 are independently at each occurrence a hydrogen, hydroxyl group, C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, or C2-C30 aromatic radicals with the proviso that R1 and R2 are not both equal to a hydroxyl group; R3 is hydrogen, a hydroxyl group, an alkoxy group, a C1-C6 hydroxyalkyl group, a C1-C6 alkyl group or a substituted alkyl group; and the summation of alkyl groups of R1, R2 and R3 is less than or equal to 16 carbon atoms; and a pharmaceutically acceptable carrier. ### Claim 37 (depends on 36) The kit of claim 36, wherein at least one of the R1 and R2 is hydrogen, C1-C30 aliphatic radicals, or C2-C30 aromatic radicals. ### Claim 38 (depends on 36) The kit of claim 36, wherein R3 is hydrogen, an alkyl group of from 1 to 6 carbon atoms, or an alkoxy group.