Targeted Radionuclide Therapy In Patient-Derived Xenografts Using Lu-177-Eb-Rgd

Currently, most patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor fiveyear 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 Lu-177-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin alpha(v)beta(3). 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 NSCLCPDX groups with intense and low expression of integrin avb3 ( denoted as PDX alpha v beta+ and PDX alpha v beta 3- ) were chosen as the experimental models to evaluate the in vivo biological behavior of Lu-177-EB-RGD. In SPECT imaging and biodistribution studies, Lu-177-EB-RGD showed significantly higher accumulation in PDX alpha v beta+ and PDX alpha v beta 3-. models than its corresponding monomer Lu-177-RGD. A single dose of 18.5 MBq Lu-177-EB-RGD was enough to completely eradicate the tumors in PDX alpha v beta+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDX alpha v beta 3-: a single dose of 29.6 MBq Lu-177-EB-RGD led to a significant delay in tumor growth as compared with that in the control or Lu-177-RGD group. The preclinical data from the use of this model suggest that Lu-177-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.