RESUMO
The epidermal growth factor receptor (EGFR) is often overexpressed during prostate cancer (PCa) progression towards androgenindependence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castrationresistant PCa. Noninvasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancerassociated molecular targets. We hypothesized that the antiEGFR affibody molecule DOTAZEGFR:2377 labeled with 55Co (positronemitter, T1/2=17.5 h) would enable imaging of EGFR expression in PCa xenografts. The human PCa cell line DU145 was used for in vitro and in vivo experiments and 57Co was used as a surrogate for 55Co in the present study. Binding of 57CoDOTAZEGFR:2377 to EGFRexpressing xenografts was saturable with antiEGFR monoclonal antibody cetuximab, which would motivate the use of this tracer for monitoring the receptor occupancy during treatment. A signiï¬cant dosedependent difference in radioactivity accumulation in tumors and normal organs was observed when the biodistribution was studied 3 h after the injection of 10 and 35 µg of 57CoDOTAZEGFR:2377: At lower doses the tumor uptake was 2fold higher although tumortoorgan ratios were not altered. For clinically relevant organs for PCa, tumortoorgan ratios increased with time, and at 24 h pi were 2.2±0.5 for colon, 7±2 for muscle, and 4.0±0.7 for bones. Small animal SPECT/CT images confirmed the capacity of radiocobalt labeled DOTAZEGFR:2377 to visualize EGFR expression in PCa. In conclusion, the present study demonstrated the feasibility of using the radiocobalt labeled antiEGFR affibody conjugate ZEGFR:2377 as an imaging agent for in vivo visualization of low EGFRexpressing tumors, like PCa, and for monitoring of receptor occupancy during cetuximab therapy as well as the importance of optimal dosing in order to achieve higher sensitivity molecular imaging.