Fractionated irradiation influences uptake of near-infrared-labeled Cetuximab: preliminaries on combination with radioimmunotherapy

External beam irradiation (EBRT) can precisely target the solid tumor mass but is limited by the surrounding normal tissue. Radioimmunotherapy mediates additional internal irradiation with the potential to strike also distant metastases. The combination of internal and external radiotherapy (CIERT) is a promising treatment strategy as it potentially combines the advantages of both modalities without increasing toxicity. In addition, patients could be stratified via a corresponding PET-tracer (1). We previously showed that CIERT using Y-90-Cetuximab (Y-90-Cet) massively increased tumor control probability compared to EBRT alone in a head and neck squamous cell carcinoma xenograft model (2). In the presented project, we investigated CIERT using clinical relevant fractionated EBRT with 30 fractions (fx) over 6 weeks. To study the best application timing, subcutaneous xenograft bearing mice were intravenously injected with near-infrared-labeled Cetuximab (NIR-Cet) at different time points during fxEBRT to model Y-90-Cet uptake. In addition, different dose groups were used for fxEBRT. NIR-Cet uptake was longitudinally followed by in-vivo optical imaging. Signal intensity was highest at day 3-4 post-injection in controls and was not altered by subsequent fxEBRT. In contrast, tumor uptake of NIR-Cet was increased if applied during fxEBRT. From these results, we concluded that low to moderate doses of fxEBRT can enhance Cet uptake but the effect is diminished if a certain threshold dose is exceeded. The interdependency of the total dose and the injection timing is not linearly and needs to be studied in more detail. However, based on the preliminary data, we injected Y-90-Cet after 10 fx of EBRT in ongoing CIERT tumor control probability experiments.

(1) Dietrich et al. Br J Radiol. 2015 Jul;88(1051):20150042
(2) Koi et al. Radiother Oncol. 2014 Feb;110(2):362-9.