Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates labeled with 177Lu: Radiolabeling and biodistribution studies
Abstrakt
Lu-177 radiolabeling of the first (G1-) or fourth (G4-) generation polyaminoamide (PAMAM) dendrimer conjugates with DOTA-like bifunctional chelator with one methylenepyridine-N-oxide pendant arm (DO3A-py(NO-C)) stability of the radiolabeled species and their pharmacokinetic characteristics were evaluated in preclinical experiments. The results showed that the G1- and G4-dendrimer conjugates, modified in average with 7.5 or 57 DO3A-py(NO-C) -c chelating units, respectively, can also be labeled with Lu-177 with a high specific activity and radiochemical purity even at 37 degrees C.
The radiolabeled species were stable for at least 24 h. Distribution profile of G1-dendrimer conjugate in organs and tissues of rats was more favorable than that of G4 one.
On the other hand, the later dendrimer conjugate bears a substantially higher number of metal chelators per molecule enabling binding of a considerably larger number of radiometals. Our results indicate that an employment of dendrimer-chelate conjugates with bound radiometals might represent a prospective way for radiolabeling of biologically active target-specific macromolecules to obtain markedly high specific activity.