177Lu-labeled cyclic Asn-Gly-Arg peptide as tumor targeting radio-nanoprobes

This study explores the potential of Lu-177-labeled carbon nanospheres as radio-nanoprobes for molecular imaging and therapy. The carboxyl functionalized surface of carbon nanospheres (CNS) was conjugated with [Gly-Gly-Gly-c(Asn-Gly-Arg)], G3-cNGR peptide through amide bond for targeting tumor vasculature and with [2-(4-Aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid], p-NH2-Bz-DOTA for chelation with Lu-177. The nanosphere-peptide conjugate, DOTA-CNS-cNGR, was characterized by dynamic light scattering and zeta potential measurements, IR and UV experiments and did not show any in vitro cytotoxicity. The pharmacokinetics and biodistribution of Lu-177-labeled nanosphere-peptide conjugate, Lu-177-DOTA-CNS-cNGR was compared with Lu-177-DOTA-CNS (without the peptide) as well as with Lu-177-DOTA-cNGR (without carbon nanospheres). The radiolabeled nanosphere-peptide conjugate exhibited higher tumor accumulation than nanosphere-free radiolabeled peptide. The accumulation of the two radiolabeled probes in the tumor reduced to half during blocking studies with unlabeled G3-cNGR peptide. Lu-177-DOTA-CNS exhibited higher tumor uptake than Lu-177-DOTA-CNS-cNGR but rapid clearance of the latter nanoprobe from non-target organs resulted in significantly higher (p<0.05) tumor-to-blood and tumor-to-muscle ratios at 24 and 48 h p.i. It is evident from this study that carbon nanospheres conjugated to specific vectors shall form an important part of targeted radionanomedicine in future. (C) 2018 Elsevier B.V. All rights reserved.