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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

Antibodies; Monoclonal/*administration & dosage/chemistry

Antineoplastic Agents/*administration & dosage

Cell Line; Tumor

Cell Membrane/metabolism

Cell Proliferation

Dose-Response Relationship; Drug

Epidermal Growth Factor/*administration & dosage/metabolism

Humans

Iodine Radioisotopes/*pharmacokinetics

Ligands

Positron-Emission Tomography

Receptor; Epidermal Growth Factor/metabolism

Receptor; erbB-2/metabolism

Time Factors

Tomography; Emission-Computed; Single-Photon

Tumor Markers; Biological

Radiation biology

Strålningsbiologi

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)