Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD.
Mol Cancer Ther
; 19(10): 2034-2043, 2020 10.
Article
de En
| MEDLINE
| ID: mdl-32847972
ABSTRACT
Currently, most patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor five-year survival rate. Therefore, intensive research aimed at finding novel therapeutic strategies has been ongoing; experimental models that reliably emulate NSCLC disease are greatly needed to predict responses to novel therapeutics. Therefore, we developed patient-derived xenograft (PDX) models of NSCLC, which we then used to evaluate the therapeutic efficacy of 177Lu-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin αvß3 In this study, three different groups of NSCLC-PDXs were successfully established, all of which maintained the same IHC and genetic characteristics of the human primary tumor. The two NSCLC-PDX groups with intense and low expression of integrin αvß3 (denoted as PDXαvß3+ and PDXαvß3-) were chosen as the experimental models to evaluate the in vivo biological behavior of 177Lu-EB-RGD. In SPECT imaging and biodistribution studies, 177Lu-EB-RGD showed significantly higher accumulation in PDXαvß3+ and PDXαvß3- models than its corresponding monomer 177Lu-RGD. A single dose of 18.5 MBq 177Lu-EB-RGD was enough to completely eradicate the tumors in PDXαvß3+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDXαvß3- a single dose of 29.6 MBq 177Lu-EB-RGD led to a significant delay in tumor growth as compared with that in the control or 177Lu-RGD group. The preclinical data from the use of this model suggest that 177Lu-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Carcinome pulmonaire non à petites cellules
/
Radiopharmaceutiques
/
Tumeurs du poumon
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Mol Cancer Ther
Sujet du journal:
ANTINEOPLASICOS
Année:
2020
Type de document:
Article
Pays d'affiliation:
Chine