Immuno-PET imaging and radioimmunotherapy of ⁶⁴Cu/¹⁷⁷Lu labeled anti-EGFR antibody in esophageal squamous cell carcinoma

Objectives Epidermal growth factor receptor(EGFR) is a valid target for targeted therapy in several tumors.Due to high frequency of EGFR expression in esophageal squamous cell carcinoma(ESCC), it is expected to treat ESCC patient with targeted therapy with anti-EGFR antibody such as cetuximab.We evaluated for feasibility of immuno-PET and radioimmunotherapy(RIT) in ESCC model using ⁶⁴Cu/¹⁷⁷Lu-cetuximab (CET).

Methods CET was conjugated with SCN-Bn-PCTA. Serum stability and immunoreactivity of ⁶⁴Cu/¹⁷⁷Lu-CET were tested.In vivo EGFR status was evaluated with Immuno-PET using ⁶⁴Cu-CET in ESCC,TE-4 and TE-8 xenografts.Biodistribution of ⁶⁴Cu/¹⁷⁷Lu-CET was performed.SPECT/CT imaging and digital whole body autoradiography(DWBA) were performed in TE-8 model.Therapeutic efficacy of ¹⁷⁷Lu-CET was evaluated and compared with cold antibody and saline in TE-8 model.Therapeutic response with FDG-PET and IHC staining was evaluated in RIT of ¹⁷⁷Lu-CET.

Results ⁶⁴Cu/¹⁷⁷Lu-CET was prepared with high radiolabeling yield and showed high stability and good immunoreactivity. Biodistribution, immuno-PET, SPECT/CT and DWBA showed specific uptake in ESCC tumor depending on EGFR expression level. Tumor peak uptake of ⁶⁴Cu-/¹⁷⁷Lu-CET was at 48 h and 120 h, respectively. ¹⁷⁷Lu-RIT group showed good tumor growth inhibition and marked reduction of FDG SUV compared to that of other groups (p<0.05). TUNEL and Ki-67 staining(%) increased and decreased, respectively, in RIT group (p<0.01) compared to other groups.

Conclusions ⁶⁴Cu-CET immuno-PET represented EGFR expression in ESCC tumor and ¹⁷⁷Lu-CET showed good radioimmunotherapeutic efficacy. Diagnostic and therapeutic radionuclide convergence radiopharmaceutical,⁶⁴Cu/¹⁷⁷Lu-PCTA-CET may be useful for a diagnostic tool in patient selection and a potent RIT agent in EGFR positive ESCC tumor.