CD31
Disclosed is CD31 shed for use as a molecular imaging target in the molecular imaging of an inflammatory condition. Administering the radiolabeled peptide P8RI as CD31 shed ligand in different rat models of inflammation indeed showed that CD31 shed is present on activated cells in a quantity allowing a detectable signal, whereas the noise signal corresponding to CD31 shed present on activated circulating cells and on other organs or cells not involved in inflammation was little. Also disclosed is a labeled CD31 shed ligand and the use thereof as a molecular imaging agent in the molecular imaging of an inflammatory condition. The molecular imaging of inflammatory sites particularly allows determining whether a subject suffers from or is at risk of having an inflammatory condition or is at risk of recurrence of an inflammatory condition after an anti-inflammatory treatment.
1. A method for imaging inflammatory sites in a subject, said method comprising:
administering to the subject a labeled CD31 shed ligand comprising a CD31 shed ligand and at least one imaging label, wherein the CD31 shed ligand is a peptide selected from the group consisting of a peptide of sequence SEQ ID NO: 2, a peptide of sequence SEQ ID NO: 3, a peptide of sequence SEQ ID NO: 4, a peptide of sequence SEQ ID NO: 5, a peptide of sequence SEQ ID NO: 6 consisting of D-enantiomer amino acids, a peptide of sequence SEQ ID NO: 7 and a peptide of sequence SEQ ID NO: 8 consisting of D-enantiomer amino acids; and
detecting the binding of the labeled CD31 shed ligand to CD31 shed by imaging the subject or at least one body part of the subject,
thereby imaging inflammatory sites in the subject.
2. The method according to claim 1 , wherein said method allows assessing the presence in the subject of an inflammatory condition, or a risk of having an inflammatory condition, and further comprises:
assessing the presence, localization and/or amount of CD31 shed by assessing the detection of the binding of the labeled CD31 shed ligand to CD31 shed in an image of the subject or of at least one body part of the subject; and
comparing said presence, localization and/or amount of CD31 shed assessed to a control biological image,
thereby determining whether the subject suffers from an inflammatory condition or is at risk of having an inflammatory condition, wherein the inflammatory condition is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, allergies, myopathy, inflammatory bowel disease, psoriasis, atopic dermatitis, cerebral amyloid angiopathy, vasculitis, systemic lupus erythematosus, Graves' disease, diabetes mellitus, acute or chronic grant rejection, cancer, thrombosis, atherothrombosis, and neurodegenerative disease.
3. The method according to claim 1 , wherein said method allows assessing the risk of recurrence of an inflammatory condition in a subject suffering from an inflammatory condition, and comprises:
administering an anti-inflammatory treatment to the subject;
carrying out the steps of the method according to claim 1 at least two times, first at the end of said anti-inflammatory treatment and then after said anti-inflammatory treatment; and
comparing the images obtained at the end of the anti-inflammatory treatment and after the anti-inflammatory treatment,
thereby determining the risk of recurrence of an inflammatory condition,
wherein the inflammatory condition is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, allergies, myopathy, inflammatory bowel disease, psoriasis, atopic dermatitis, cerebral amyloid angiopathy, vasculitis, systemic lupus erythematosus, Graves' disease, diabetes mellitus, acute or chronic grant rejection, cancer, thrombosis, atherothrombosis, and neurodegenerative disease.
4. The method according to claim 1 , wherein said method allows monitoring efficacy of an anti-inflammatory treatment administered to a subject suffering from an inflammatory condition, and comprises:
carrying out the steps of the method according to claim 1 ;
administering an anti-inflammatory treatment to the subject;
repeating the steps of the method according to claim at least once during administration of the treatment; and
comparing the images obtained before administration of the anti-inflammatory treatment and during administration of the anti-inflammatory treatment,
thereby monitoring efficacy of the anti-inflammatory treatment,
wherein the inflammatory condition is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, allergies, myopathy, inflammatory bowel disease, psoriasis, atopic dermatitis, cerebral amyloid angiopathy, vasculitis, systemic lupus erythematosus, Graves' disease, diabetes mellitus, acute or chronic grant rejection, cancer, thrombosis, atherothrombosis, and neurodegenerative disease.
5. The method according to claim 1 , wherein said CD31shed ligand is a peptide of sequence SEQ ID NO: 5, a peptide of sequence SEQ ID NO: 6 consisting of D-enantiomer amino acids, a peptide of sequence SEQ ID NO: 7, or a peptide of sequence SEQ ID NO: 8 consisting of D-enantiomer amino acids.
6. The method according to claim 1 , wherein said imaging label is a radionuclide.
7. The method according to claim 1 , wherein said imaging label is a radionuclide detectable by Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), a hybrid of SPECT and/or PET or their combinations.
8. The method according to claim 1 , wherein said imaging label is a radionuclide selected from the group consisting of technetium-99m (99mTc), gallium-67 (67Ga), gallium-68 (68Ga) yttrium-90 (90Y), indium-111 (111In), rhenium-186 (186Re), fluorine-18 (18F), copper-64 (64Cu), and thallium-201 (201T1).
9. The method according to claim 1 , wherein said CD31 shed ligand is a peptide of sequence SEQ ID NO: 6 consisting of D-enantiomer amino acids, or a peptide of sequence SEQ ID NO: 8 consisting of D-enantiomer amino acids, and wherein said imaging label is a radionuclide being 99mTc.
10. The method according to claim 1 , wherein said CD31 shed ligand comprises 6-hydrazinopyridine-3-carboxylic acid (HYNIC).
11. An in vitro method for detecting CD31 shed in a biological sample of a subject, said biological sample comprising cells, wherein said method comprises:
contacting the biological sample of the subject with a labeled CD31 shed ligand comprising a CD31 shed ligand and at least one imaging label, wherein said CD31 shed ligand is a peptide selected in the group consisting of a peptide of sequence SEQ ID NO: 2, a peptide of sequence SEQ ID NO: 3, a peptide of sequence SEQ ID NO: 4, a peptide of sequence SEQ ID NO: 5, a peptide of sequence SEQ ID NO: 6 consisting of D-enantiomer amino acids, a peptide of sequence SEQ ID NO: 7 and a peptide of sequence SEQ ID NO: 8 consisting of D-enantiomer amino acids; and
imaging the labeled CD31 shed ligand bound to CD31 shed , thereby detecting the presence of CD31 shed on the surface of the cells comprised within the biological sample of the subject.
12. The method according to claim 11 , wherein said CD31 shed ligand is a peptide of sequence SEQ ID NO: 6 consisting of D-enantiomer amino acids, or a peptide of sequence SEQ ID NO: 8 consisting of D-enantiomer amino acids, and wherein said imaging label is a radionuclide being 99mTc.