Subprogram 4

Developing of radiolabelling approaches of molecular and supramolecular carriers and PET imaging

Labelling with reactor or generator produced radionuclides is an essential part of this project. Similar labelling approaches can be anticipated for molecular and supramolecular carriers, although, differences do exist. This subprogram will be carried out mainly at JOGU Mainz with the exception of radiolabelling with alpha emitters, which will be carried in collaboration with the Alphaimmunotherapy group (ITU) and performed in subprogram 5.

Radiolabelling with PET isotopes will be carried out using two different approaches: the novel versatile fluorine-18 labelling strategy that has been previously applied to HPMA-based polymers and the fluorine-18 labelling of polymeric supramolecular carriers based on the copper-catalyzed Huisgen 1,3-dipolar cycloaddition (“click chemistry”).

Beside these approaches the research will concentrate on the use of metallic radionuclides for the in vivo evaluation of carriers via chelation. The connection of the nuclides via chelators is versatile, allowing the chelation of diagnostic as well as therapeutic trivalent radiometals by the same chelator e.g. DOTA. Using radiometals with longer half lives, e.g. generator produced scandium-44 (t1/2=3,9 h, 86% β+-emission), long-term visualization of radiolabelled nano-carriers in vivo can be accomplished, which helps in understaning passive accumulation processes like the EPR effect of macromolecules in tumour tissue.

Radiolabelled molecular and supramolecular carriers will be delivered during this subprogram for in vitro and vivo evaluation.

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