New cyclam-based chelate derivatives for cancer diagnostic and/or therapeutic applications

The work consisted in the development of chelates based on π-extended picolinate cyclam derivatives giving access to luminescent complexes for applications in medical imaging and/or therapy. For a specific use for biphotonic microscopy, an Yb³⁺ reinforced cyclam complex functionalized by two π-extended picolinate units has been synthesized. The simultaneous presence of a lanthanide ion emitting in the NIR and an antenna allowing two-photon absorption, gave rise to cellular images recorded in the NIR-to- NIR channel. The luminescent properties of π-extended picolinate antennas have also been used for the development of bimodal PET/optical imaging probes. Cyclam-based ligands have been functionalized with a picolinate fluorophore and have been used for the complexation of Cu²⁺ which has a β⁺-emitting isotope. If the radiolabeling of the ligands with ⁶⁴Cu²⁺ could be carried out, spectroscopic studies of the Cu²⁺ complexes demonstrated that the metal inhibits the luminescent properties of the fluorophore. However, preliminary studies have shown that Ga³⁺, which also has a β⁺-emitting isotope, may be a relevant alternative to Cu²⁺. Finally, the substitution of the π-conjugated system by the incorporation of a dibromobenzene unit gives access to a photosensitizer capable of generating cytotoxic singlet oxygen for a use in photodynamic therapy (PDT). This type of photosensitizer can also be introduced on the picolinate moiety to give Cu²⁺ chelates for an application in TEP/PDT theranostic. Again, the influence of the metal center on the photophysical properties of the resulting complex could be highlighted. (author)