Untersuchungen zur kombinierten internen-externen Radiotherapie (CIERT) am Zellmodell

Zusammenfassung

Ziel: Eine kombinierte interne-externe Radiotherapie (CIERT) erfordert eine einheitliche Betrachtung der biologischen Strahlenwirkung. Dafür sollte der Formalismus der Biologisch Effektiven Dosis (BED) am Zellmodell überprüft werden. Methoden: NIS-positive Schilddrüsenzellen FRTL-5 wurden mit Röntgenstrahlung oder/und mit Tc-99m-Pertechnetat bestrahlt. Anoder Abwesenheit von Perchlorat konnte die aktive zelluläre Aufnahme des Radiotracers während 24 h Bestrahlungsdauer verhindern oder zulassen. Die Dosisbestimmung für die Radionuklidbestrahlung erfolgte auf Basis gemessener Uptakewerte mittels Monte-Carlo-Simulation. Aus Dosiswirkungskurven mit Koloniebildungs-Assay als biologischem Endpunkt wurden zellspezifische radiobiologische Parameter abgeleitet. Für Kombinationsbestrahlungen unter Variation von Reihenfolge und Zeitabstand wurde das Zellüberleben mit Vorhersagewerten des BED-Formalismus verglichen. Ergebnisse: Die für Röntgenbestrahlung ermittelten Parameter α = (0,22 ± 0,02) Gy^-1, β = (0,021 ± 0,001) Gy^-2 und Reparaturhalbwertszeit (1,51 ± 0,21) h erklären auch die Dosiswirkungskurven für Tc-99m-Pertechnetat mit exponentiell fallender Dosisleistung. Die CIERT-Experimente zeigten keine signifikanten Unterschiede bezüglich Reihenfolge und Bestrahlungspause, jedoch bei Radionuklidaufnahme in die Zellen ein geringeres Überleben als durch die BED vorhergesagt. Schlussfolgerung: Am Zellmodell konnte verifiziert werden, dass die BED grundsätzlich zur Beschreibung von biologischen Strahleneffekten bei unterschiedlichen Strahlenqualitäten und Dosisleistungen anwendbar ist. Ob bei intrazellulärer Radionuklidaufnahme in Kombination mit Röntgenbestrahlung supraadditive Effekte entstehen, die auf Auger- und Konversionselektronen des Tc-99m zurückzuführen sind, bedarf weiterer Experimente.

Summary

Aim: Combined internal-external radiotherapy (CIERT) requires a unified assessment of biologic radiation effects in addition to the total dose. The concept of biological effective dose (BED) was evaluated in a cell model. Methods: The thyroid NIS-positive cell line FRTL-5 was irradiated with X-ray and the radiotracer Tc-99m pertechnetate either alone or in combination. The cellular uptake of the radionuclide during the incubation time of 24 h was controlled by the presence or absence of perchlorate. Dose calculation was performed based on measured uptake values. Cell specific radiobiologic parameters were derived from dose effect curves using the colony forming assay as biological endpoint. For the combination of the radiation qualities the sequence and time difference were varied. Cell survival was compared with the prediction of the BED model. Results: The radiobiologic parameters from X-ray dose response were α = (0.22 ± 0.02) Gy^-1 and β = (0.021 ± 0.001) Gy^-2. The half life for repair was (1.51 ± 0.21) h. These values could also explain the dose response curves for Tc-99m-irradiation with exponential decreasing dose rate. CIERT experiments showed no significant differences in cell survival regarding sequence and irradiation break. When the radionuclide uptake was not prevented the cell survival for the combination of X-ray and Tc-99m was lower than the prediction by BED calculations. Conclusions: The validity of the BED formalism for different dose rates and radiation qualities was verified. Supraaddive effects measured in the combination of X-ray and intracellular Tc-99m might be caused by Auger and conversion electrons, however further experiments are necessary.

Schlüsselwörter

Koloniebildungs-Assay - Uptake - Tc-99m - Auger- Elektronen - FRTL-5

Keywords

Colony forming assay - uptake - Tc-99m - Auger electrons - FRTL-5

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