Summary

A novel EGFR-targeted radiotheranostic agent, ²⁰³Pb-PSC-panitumumab, was evaluated using SPECT/CT imaging in NRG mice bearing subcutaneous EGFR-positive HNSCC PDX tumors. High-resolution nanoScan® SPECT/CT imaging was performed at 48 and 120 hours post-injection to assess biodistribution and tumor localization. The observed tumor accumulation and retention confirmed the potential of this radioligand for future development of ²¹²Pb-based targeted alpha therapy.

Results with nanoScan® SPECT/CT

The ²⁰³Pb and ²¹²Pb isotopes share identical chemistry, allowing SPECT imaging with ²⁰³Pb to accurately reflect the biodistribution of ²¹²Pb-based targeted alpha therapy, enabling more precise and personalized treatment. Advances in generator technology have made ²¹²Pb readily available, making this theranostic pair a promising and competitive alternative to currently used ²²⁵Ac-based therapies.

Radiolabelling with ²⁰³Pb was achieved with high efficiency, as confirmed by radio-TLC and SDS-PAGE analyses demonstrating stable incorporation of the radionuclide into the PSC-conjugated panitumumab. (Fig. 1)

Fig.1. The ²⁰³Pb-PSC-panitumumab was produced with 41.5 ± 8% yield, >99% purity, and >95% stability in human serum over 48 hours.

Cellular uptake of ²⁰³Pb-PSC-panitumumab in EGFR-expressing FaDu cells increased over time, reaching a plateau at 60 minutes. Specificity was confirmed by blocking studies, showing up to 95% inhibition with increasing panitumumab concentrations, while the immunoreactive fraction was approximately 30%. (Fig.2)

Fig. 2. Cellular uptake and competitive binding studies confirmed specific EGFR targeting of ²⁰³Pb-PSC-panitumumab in FaDu cells, supported by Lindmo assay results.

SPECT/CT imaging was performed using the Mediso nanoScan® SPECT/CT system to visualize the biodistribution of ²⁰³Pb-PSC-panitumumab in mice bearing EGFR-positive HNSCC tumors, with clear tumor localization observed at both 48 and 120 hours post-injection. Under EGFR blocking conditions, SPECT/CT images demonstrated a significant reduction in tumor uptake accompanied by increased radioactivity in the heart and blood pool, indicating effective receptor blockade. The remaining tumor radioactivity detected despite blocking is attributed to the enhanced permeability and retention (EPR) effect, a phenomenon commonly observed in immunoPET and immunoSPECT imaging of solid tumors. These results highlight the selective and sustained tumor targeting capability of ²⁰³Pb-PSC-panitumumab and underscore the utility of this radioligand for specific imaging of EGFR-expressing tumors using the Mediso nanoScan® platform. (Fig.3)

Fig. 3. SPECT/CT images showing NRG mice with EGFR-positive HNSCC PDX tumors at 48 and 120 hours post-injection, comparing control and blocking groups; tumor locations are marked with arrows.

Conclusion

The use of the nanoScan SPECT/CT system enables high-resolution, non-invasive imaging of ²⁰³Pb-PSC-panitumumab biodistribution and tumor uptake in vivo, providing precise anatomical localization alongside functional data. Its sensitivity and quantitative capabilities allow for detailed monitoring of EGFR-positive tumors over time, making it an excellent platform for evaluating novel immuno-SPECT probes and supporting the development of personalized radiotheranostic strategies.

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