[177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

摘要: Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance inactivating single tumor cells minimal damage surrounding healthy tissue. As target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand EGFR, (EGF) is an attractive agent its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) well suited treatment small cell clusters, since it emits relatively low-energy beta particles. goal this study was prepare preclinically evaluate both in vitro vivo [177Lu]Bz-DTPA-EGF conjugate. conjugate characterized cell-binding properties, pharmacokinetics ability target bound cultured U343 1.9 nM. Interaction EGFR led rapid internalization, more than 70% cell-associated radioactivity internalized after 30 minutes incubation. retention good, 65% still 2 days. Biodistribution studies i.v. injected NMRI mice demonstrated blood clearance. Most found liver kidneys. uptake receptor-mediated, could significantly reduced by preinjection unlabeled EGF. In conclusion, seems promising candidate locoregional binding affinity, weight, vivo.