177Lu-Labeled Cyclic Rgd Peptide As an Imaging and Targeted Radionuclide Therapeutic Agent in Non-Small Cell Lung Cancer: Biological Evaluation and Preclinical Study Publisher Pubmed



Pirooznia N¹ ; Abdi K¹ ; Beiki D² ; Emami F³ ; Arab SS⁴ ; Sabzevari O⁵ ; Soltanigooshkhaneh S³
Source: Bioorganic Chemistry Published:2020

Abstract

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80–85% of death. αvβ3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of αvβ3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK)2 with 177Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of −3.878 was obtained for 177Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (Kd) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing αvβ3 integrin receptors. © 2020 Elsevier Inc.