Funding (ICMUB): 200 000 €
Duration: Jan. 2025 – 42 months
Scientific Leader ICMUB : Victor GONCALVES (PI of the project)
Summary
Nuclear imaging is now a key component of patient management. Monoclonal antibodies are the carriers of choice for molecular imaging, due to their exceptional affinity and selectivity for their target antigen. However, due to their large size, they diffuse poorly into tissues and are slowly eliminated. Therefore, they are traditionally radiolabeled with long half-life radioisotopes (e.g. 89Zr), responsible for indiscriminate irradiation of all organs. Moreover, sufficient contrast for imaging is only achieved several days after administration of the radioimmunoconjugate.
The SUPRALABEL project aims at developing a strategy known as “pretargeting”, in which the radiolabeling of the antibody is not carried out prior to administration to the patient, but is performed in vivo, once the antibody has optimally accumulated in the target tissue and has been eliminated from healthy tissues. This approach thus allows the use of short half-life radioisotopes such as 68Ga and 18F, which are the most relevant isotopes for clinical application. Pretargeting requires the use of highly reactive and selective partners, so that the conjugation reaction between the antibody and the radioactive probe can take place rapidly, in a particularly complex biological environment, such as the human body. Here, we aim to exploit the unique affinity between two small molecule partners, cucurbit[7]uril and adamantanamine, to form these radioimmunoconjugates in vivo by supramolecular assembly. We aim to develop cucurbit[7]uril radiolabeled with gallium-68 and fluorine-18 and optimize their pharmacokinetic properties in order to make them suitable for the pretargeting strategy. The added-value of the pretargeting strategy in immunoPET, in terms of dosimetry for the patient, will be demonstrated by the targeting of the protein LOXL2 on a murine model of pulmonary fibrosis.
Legend : A) Concept of in vivo pretargeting for nuclear imaging. B) Structures of the supramolecular partners used in the SUPRALABEL project.
Total Funding: 540 000 €
Partners:
- CEA Saclay – Laboratoire BIOMAPS (Simon SPECKLIN)
- CGFL – IMATHERA (Pierre-Simon BELLAYE)