A review of chelators used for Technetium 99m/Rhenium 188 labelling of peptides and proteins

Thumbnail Image
Journal Title
Journal ISSN
Volume Title
Molecular imaging is rarely seen in Single Photon Emission Computed Tomography (SPECT) studies, instead, the majority of studies conducted in nuclear medicine are functional scans. This is due to the slow development in the radiopharmacy aspect of nuclear medicine, in particular, the chemistry of labelling biomolecules (BM) with SPECT radionuclides such as generator-produced radionuclides Technetium (Tc) and Rhenium (Re). Indirect labelling of BM with Tc/Re requires the use of bifunctional chelators (BFC) such as Hydrazine nicotinamide (HYNIC) Tricarbonyl, and tetraamine. HYNIC has been researched extensively due to its fast labelling at a low concentration, however, HYNIC is not stable in vivo and forms multiple isomers, which is problematic. Tricarbonyl demonstrates high kinetic stability, but tricarbonyl limited by the multi-step synthesis, complexity of production, conditions required for labelling and lipophilicity which has unfavoured biodistribution with Tricarbonyl 99mTc(CO)3. On the other hand, tetraamine-based BFC, 1,4,8,11-tetraazaundecane (TAU), has shown high kinetic stability, specific activity and hydrophilicity, and does not have the isomerism problem like HYNIC. Unfortunately, TAU-based conjugates have not found widespread use due to the complexity of synthesis and insufficient information in the literature about it.