Lutetium coordination compounds toward potential nanoradiopharmaceutical applications: Rational design and synthesis

Radiolabelled nanoparticles (nanoradiopharmaceuticals) merge the advantages of radiopharmaceuticals and nanoparticles. Among them, polymeric nanoparticles (PNp) can be designed and prepared with architecture, surface charge and functionalization according to applications. Lu-177 is a radionuclide widely used for the preparation of nanoradiopharmaceuticals due to its theranostic properties. PNp are loaded with a therapeutic agent while 177Lu is usually indirectly bonded to PNp-surface, mostly through bifunctional chelating agents such as DOTA and its derivatives. However, the use of these derivatives typically does not yield a high specific activity of the radiolabelled-PNp. A strategy to increase the specific activity of these nanosystems is implementing direct radiolabelling methodologies which bind 177Lu into the PNp surface. The aim of this study was to design and propose, aided by computational chemistry tools, a labelling strategy for PNp systems. Molecules selected for complexing Lu were bidentate and tridentate ligands. Such ligands together should close the 177Lu coordination sphere to form Lu-complexes with near Lu-DOTA stability constant. The combinations of ligands (glycine, diethylenetriamine, lactic acid, glycolic acid, ascorbic acid, poly(lactic-co-glycolic acid) (PLGA) and poly(L gamma-glutamic acid) (gamma-PGA) have the desired characteristics and also are frequently used in the preparation of PNp, another feature sought in the ligand selection. The potential formation of Lu-complex using the aforementioned compounds were simulated (with non -radioactive atom) under standard conditions and in aqueous media at different temperatures. Four of the simulated complexes were prepared in acid media (also with a nonradioactive atom) and their potentiometric and spectrophotometric responses were followed during titration with NaOH. Experimental results showed the formation of 3 different complexes with probable coordination number 8, one of which shows possibilities as a potential candidate to assemble 177Lu-PNp.