Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor

Purpose The purpose of this study was to analyse whether non-radiolabelled epidermal growth factor (EGF) can modify the cellular uptake of ¹²⁵I when delivered as [¹²⁵I]trastuzumab. ¹²⁵I was used as a marker for the diagnostically and therapeutically more interesting isotopes ¹²³I (SPECT), ¹²⁴I (PET) and ¹³¹I (therapy).Methods The cell-associated radioactivity was measured in squamous carcinoma A431 cells following addition of [¹²⁵I]trastuzumab. Different concentrations of [¹²⁵I]trastuzumab and unlabelled EGF were used, and the total, membrane-bound and internalised radioactivity was measured. We also analysed how EGF and trastuzumab affected the cell growth. Results It was generally found that the cellular ¹²⁵I uptake was decreased by the addition of EGF when [¹²⁵I]trastuzumab was added for short incubation times. However, if the incubation times were longer, EGF increased the ¹²⁵I uptake. This shift came earlier when higher [¹²⁵I]trastuzumab concentrations were applied. The addition of EGF also influenced cell proliferation, and concentrations above 10 ng/ml reduced cell growth by approximately 20% after 24 h of incubation.Conclusion By adding unlabelled EGF, it was possible to modify the cellular uptake of [¹²⁵I]trastuzumab. This points towards new approaches for the modification of radionuclide uptake in EGFR- and HER2-positive tumours.