Cd31shed as a molecular target for imaging of inflammation

Abstract

Disclosed is CD31shed for use as a molecular imaging target in the molecular imaging of an inflammatory condition. Administering the radiolabeled peptide P8RI as CD31shed ligand in different rat models of inflammation indeed showed that CD31shed is present on activated cells in a quantity allowing a detectable signal, whereas the noise signal corresponding to CD31shed present on activated circulating cells and on other organs or cells not involved in inflammation was little. Also disclosed is a labeled CD31shed 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 labeled CD31 shed  ligand comprising a CD31 shed  ligand and at least one imaging label. 
     
     
         2 . The labeled CD31 shed  ligand according to  claim 1 , wherein said CD31 shed  ligand is a peptide, a peptidomimetic, a chemical compound, an antibody, or an aptamer. 
     
     
         3 . The labeled CD31 shed  ligand according to  claim 1 , wherein said CD31 shed  ligand is a single domain antibody or a scFv fragment. 
     
     
         4 . The labeled CD31 shed  ligand according to  claim 1 , wherein said CD31 shed  ligand is
 a) a peptide selected in the group consisting of:
 (i) a peptide consisting of a fragment of 3 to 15 amino acids of the sequence defined by amino acids 579 to 601 of sequence SEQ ID NO: 1, 
 (ii) a peptide consisting of a fragment of 3 to 15 amino acids of a sequence corresponding to the amino acids 579 to 601 of sequence SEQ ID NO: 1 in a non-human mammalian CD31, 
 (iii) a peptide of 3 to 15 amino acids consisting of a sequence at least 70% identical to the sequence of peptide (i), 
 (iv) a peptide consisting of a retro-inverso sequence of peptide (i), (ii), or (iii), and 
 (v) the peptide (i), (ii), (iii), or (iv) comprising at least one chemical modification, 
   or   b) a peptidomimetic of peptide a).   
     
     
         5 . The labeled CD31 shed  ligand according to  claim 1 , 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. 
     
     
         6 . The labeled CD31 shed  ligand according to  claim 1 , wherein said CD31 shedl  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. 
     
     
         7 . The labeled CD31 shed  ligand according to  claim 1 , wherein said imaging label is a radionuclide. 
     
     
         8 . The labeled CD31 shed  ligand 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. 
     
     
         9 . The labeled CD31 shed  ligand 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 (201Tl). 
     
     
         10 . The labeled CD31 shed  ligand according to  claim 1 , wherein said imaging label is 99mTc. 
     
     
         11 . The labeled CD31 shed  ligand according to  claim 1 , 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 wherein said imaging label is a radionuclide. 
     
     
         12 . The labeled CD31 shed  ligand 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 99mTc. 
     
     
         13 . The labeled CD31 shed  ligand according to  claim 1 , wherein said CD31 shed  ligand comprises 6-hydrazinopyridine-3-carboxylic acid (HYNIC).