Resumen
The present invention relates to imaging probes, preferably radioactive compounds, (also referred to in the present invention as radiotracers) comprising a protein, preferably selected from the list consisting of collagen, fibronectin, and fibrinogen. In a particular embodiment, said protein is covalently bonded to a chelating agent and a radioisotope coordinated to the chelating agent. The present invention also relates to the method of preparation of the compounds and the use of the compounds for the non-invasive detection of infection sites caused by Gram+ bacteria by means of imaging techniques, such as nuclear imaging.
Reivindicaciones
1. 27 CLAIMS 1. A radiolabeled compound comprising a protein which is a substrate of the microbial surface component recognizing adhesive matrix molecules (MSCRAMMs), preferably the protein is selected from the list consisting of collagen, fibronectin, and fibrinogen, or derivatives thereof which maintain the respective binding properties. 2. A compound according to claim 1 , wherein said protein is covalently bonded to a chelating agent and a radioisotope coordinated to the chelating agent. 3. The compound according to any of claims 1 or 2, wherein the protein is collagen, preferably the collagen is a type I or type IV collagen. 4. The compound according to any of the preceding claims 1 to 3, wherein the chelating agent is selected from the list comprising: - pentetic acid, - 1 ,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA) and its derivatives: DOTA-NHS ester, maleimide-DOTA, and NH2-DOTA-GA; - 1 ,4,7-triazacyclononane-1 ,4,7-triacetic acid (NOTA) and its derivatives: NOTA-NHS ester, NODAGA-NHS ester, maleimide-NOTA, and NH2-NODA-GA; - deferoxamine (DFO) and its derivative p-SCN-Bn-deferoxamine; - diethylenetriamine-N,N,N”,N”-tetra-tert-butyl acetate-N’-acetic acid; preferably, wherein the chelating agent is pentetic acid. 5. The compound according to any of the preceding claims 1 to 4, wherein the radioisotope is selected from the list consisting of<99m>Tc,<68>Ga,<18>F,<89>Zr,<64>Cu,<131>1,<124>l or<111>In; preferably the radioisotope is<99m>Tc. 6. A method for preparing the compound defined in any of claims 2 to 5 comprising a first step of forming a covalent bond between the protein and the chelate, a proteinchelate conjugate thus being formed, and a second step based on radioactively labeling the protein-chelate conjugate with the corresponding radioisotope, optionally the obtained radiolabeled protein-chelate conjugate is purified. 7. A composition comprising the compound described in any of the preceding claims 1 to 5. 8. The composition according to claim 7, characterized by being configured for being able to be administered intravenously, intraperitoneally, or orally. 9. Use of a compound comprising a protein which is a substrate of the microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) labelled with a marker suitable for detection by imaging techniques as an imaging agent for the visualization of infections or infection sites caused by Gram-positive bacteria in a subject. 10. Use of the compound described in any of claims 1 to 5, or of the composition described in claim 7 or 8, as an imaging agent for the visualization of infections or infection sites caused by Gram-positive bacteria in a subject. 11. Use according to any of claims 9 or 10, wherein the Gram-positive bacteria are selected from the genus Staphylococcus, Streptococcus, Enterococcus, Mycobacterium, Bacillus and Clostridioides, preferably from the list consisting of Staphylococcus aureus, Staphylococcus epidermis, Streptococcus mutans, Mycobacterium tuberculosis, Enterococcus faecalis, Staphylococcus agalactiae, Bacillus anthracis and Clostridioides difficile. 12. Use according to any of claims 9 or 10, wherein the Gram-positive bacteria are Gram-positive cocci, preferably selected from the genus Staphylococcus, Enterococcus or Streptococcus. 13. Use according to any of claims 9 to 12, wherein the infection caused by Grampositive bacteria is infective endocarditis. 14. Use according to any of claims 9 to 13, wherein the visualization of infections or infection sites is performed by means of scintigraphy, PET or SPECT imaging, optionally combined with a structural technique such as computed tomography or magnetic resonance imaging. 15. A method for providing an image of infection sites caused by Gram-positive bacteria in vivo in a subject, which comprises scanning a subject, to which the compound as defined in any of claims 1 to 5 has been administered, by using an imaging technique to obtain a visible image. 16. The method according to claim 15, wherein said imaging technique is a nuclear imaging technique, such as scintigraphy, PET or SPECT imaging, optionally combined with a structural technique such as computed tomography or magnetic resonance imaging.
