Influence of time-dose-relationships in therapeutic nuclear medicine applications on biological effectiveness of irradiation

Summary

Aim: The biological effectiveness of irradiation is influenced not only by the total dose but also the rate at which this dose is administered. Tolerance dose estimates from external radiation therapy with a conventional fractionation protocol require adaptation for application in targeted radionuclide therapy. Methods: The linear-quadratic model allows for calculation of the biologically effective dose (BED) and takes into consideration tissue specific factors (recovery capacity) as well as dose rate effects (recovery kinetics). It can be applied in radionuclide therapy as well. For relevant therapeutic radionuclides (e. g. ¹⁸⁸Re, ⁹⁰Y, ¹⁷⁷Lu, and ¹³¹I), the effect of different physical decay times and variable biological half-lives on BED was calculated for several organs. Results: BED is markedly increased using ¹⁸⁸Re compared to longer-lived radionuclides. The effect is dose-dependent and tissue-specific, resulting, for example, in higher effects on the kidneys compared to bone marrow. Therefore, in unfavourable conditions (e. g. reduced recovery capacity due to concomitant diseases or previous therapy), the BED may exceed organ dose tolerance. Conclusion: Time-dose-relationships have to be taken into consideration by the calculation of BED for internal radionuclide therapy. The biological effectiveness depends on dose- and tissue-specific factors and is much more pronounced in ¹⁸⁸Re than in ⁹⁰Y and other longer living radionuclides. Determination of organ tolerance dose values should take into account these radiobiological differences, since it is currently not considered in dosimetry programs.

Zusammenfassung

Ziel: Die biologische Wirkung einer Bestrahlung wird nicht nur durch die Höhe der Dosis, sondern auch durch die Dauer und zeitabhängige Dosisleistung der Dosisapplikation bestimmt. Toleranzdosen, die aus externer Bestrahlung mit einer konventionellen Fraktionierung ermittelt wurden, benötigen eine Anpassung für die Anwendung bei der Therapie mit offenen Radionukliden. Methoden: Das linearquadratische Modell ermöglicht die Berechnung der BED (biologisch effektive Dosis) und berücksichtigt gewebespezifische Faktoren (Erholungskapazität) sowie Zeitfaktoren (Erholungskinetik). Es kann auch für die Therapie mit offenen Radionukliden angewendet werden. Für die therapeutisch nutzbaren Radionuklide ¹⁸⁸Re, ⁹⁰Y, ¹⁷⁷Lu und ¹³¹I wurde so der Effekt ihrer unterschiedlichen physikalischen und biologischen Halbwertszeiten auf die BED in verschiedenen Organen simuliert. Ergebnisse: Die BED bei der Therapie mit ¹⁸⁸Re ist gegenüber längerlebigen Therapienukliden deutlich erhöht. Der Effekt ist dosisabhängig und gewebespezifisch und beispielsweise an der Niere sehr viel ausgeprägter als am Knochenmark. Unter ungünstigen Bedingungen (z. B. verminderte Toleranz oder Erholungskapazität bei Begleiterkrankungen oder vorausgegangener Therapie) kann die BED die Organtoleranzdosis übersteigen. Schlussfolgerung: Die Dosisleistung einer Therapie mit offenen Radionukliden sollte durch die Berechnung der BED berücksichtigt werden. Der Effekt ist dosisabhängig und gewebespezifisch und bei ¹⁸⁸Re sehr viel höher ausgeprägt als bei ⁹⁰Y und längerlebigen Nukliden. Bei der Festlegung von Dosisgrenzwerten müssen diese Unterschiede in der biologischen Wirkung beachtet werden, gängige Dosimetrieprogramme berücksichtigen dies bislang nicht.

Keywords

Biological effective dose - dosimetry - ¹⁸⁸Re - nephrotoxicity - isoeffectiveness

Schlüsselwörter

Biologisch effektive Dosis - Dosimetrie - ¹⁸⁸Re - Nephrotoxizität - Isoeffektivität

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