Kleintierdosimetrie für die diagnostische PET Bildgebung

Zusammenfassung

Vor der erstmaligen Anwendung neuartiger Radiopharmazeutika für die PET Bildgebung im Menschen muss deren Strahlenrisiko abgeschätzt werden. Neben ex vivo Methoden, welche die Verwendung von Tieren voraussetzt, bieten bildgebende in vivo Methoden unter Nutzung entsprechender Kleintierscanner die Möglichkeit Langzeitstudien durchzuführen und die Tiere für weitere Versuche zu verwenden. Aktuell stehen verschiedene kommerziell erhältliche PET Kameras speziell für Mäuse und Ratten zur Verfügung. Größere Spezies wie z. B. Ferkel können in humanen PET Scannern untersucht werden.

Bei der Verwendung von anhand Tieren erhobener Daten für die Dosisabschätzung im Menschen, müssen deren Biokinetik auf den Menschen extrapoliert werden, um Unterschiede im Metabolismus und der Anatomie auszugleichen. Die anschließende Organdosisberechnung kann mit Hilfe verschiedener Software erfolgen (z. B. Olinda) und die effektive Dosis als Maß des kumulierten Strahlenrisikos abgeschätzt werden.

Die Durchführung einer präklinischen Dosimetriestudie dient dem Ziel einer Abschätzung des Strahlenrisikos für das Individuum nach Inkorporation eines Radiopharmazeutikums. Es können kritische Organe und der Ausscheidungsweg identifiziert werden, jedoch sollten die Ergebnisse einer präklinischen Dosimetriestudie immer mit Hinblick auf die methodischen Limitationen betrachtet werden. Aktuelle Untersuchungen zeigen eine Unterschätzung der Exposition um bis zu 40 % und dies sollte bei der Beantragung einer frühen klinischen Studie berücksichtig werden.

Abstract

Before novel radiopharmaceuticals can be applied for PET imaging in humans for the first time, their radiation risk must be assessed using suitable animal models. In addition to ex vivo methods, which require to sacrifice the animals, in vivo imaging methods using appropriate small animal scanners offer the possibility of conducting long-term studies and using the animals for further experiments again. Various PET cameras dedicated for mice and rats are commercially available. Larger species such as piglets can be measured in human PET scanners for deriving the biokinetic data.

When using animal data for dose estimation in humans, their biokinetics must be extrapolated to human entity to compensate for differences in metabolism and anatomy. The subsequent organ dose calculation can be carried out using various software (e. g. Olinda) and the effective dose can be estimated as a measure of the cumulative radiation risk.

Carrying out preclinical dosimetry calculations serve the purpose of estimating the radiation risk after the incorporation of a radiopharmaceutical. Critical organs and the route of excretion can be identified, but the results of a preclinical dosimetry study should always be considered with regard to the methodological limitations. Recent studies show an underestimation of exposure by up to 40 % and this should be taken into account when applying for first-in-man studies.

Schlüsselwörter

Kleintier PET - präklinische Dosimetrie - Strahlungsdosimetrie - PET/MRI - PET/CT

Keywords

small animal PET - preclinical dosimetry - radiation dosimetry - PET/MRI - PET/CT

Publication History

Article published online:
21 March 2023

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