Dosimetrie bei der Radionuklidtherapie mit Lu-177

Zusammenfassung

Die Radioligandentherapie (RLT) mit radioaktiv markierten PSMA-Liganden (z. B. Lu-177-PSMA-617) und die Peptid-Rezeptor-Radionuklidtherapie (PRRT) mit radioaktiv markierten Somatostatin-Analoga (z. B. Lu-177-DOTATATE) haben sich über die letzten Jahre als vielversprechende Therapieoptionen bei metastasierten, kastrationsresistenten Prostatakarzinomen bzw. inoperablen oder metastasierten neuroendokrinen Tumoren entwickelt. Das Theragnostiknuklid Lu-177 weist dabei neben der Therapie-relevanten Beta-Minus-Komponente eine, auch für die Bildgebung gut nutzbare, Gammaemission auf, die eine direkte quantitative Bildgebung und Dosimetrie der Radiopharmakonverteilung möglich macht. Die Patienten-spezifische 3D-Dosimetrie auf Basis der quantitativen Lu-177-Bildgebung ist dabei der Schlüssel hin zur individualisierten Therapiekontrolle und -planung in der RLT und PRRT, in denen bisher vornehmlich noch standardisierte Aktivitätsmengen verabreicht werden. Jedoch ist die Ermittlung robuster Dosiswerte klinisch aufwändig, sowohl bez. des Messaufwands als auch hinsichtlich der Auswertung der Daten, und die starke Variabilität der Dosiswerte und deren Abhängigkeit von der verwendeten Methodik erschweren die Etablierung Therapie-spezifischer Dosis-Wirkungsbeziehungen. Gerade der Vergleich von Dosimetriedaten zwischen den Kliniken erfordert eine systematische und vereinheitlichte Dosimetrie mit akzeptablem klinischem Aufwand. Die Genauigkeit der Dosimetrie ist derzeit v. a. limitiert durch Effekte der Bildgebung. Zusätzliche Fehler können sich bspw. durch eine ungünstige Wahl der gemessenen Datenpunkte, Bewegungsartefakte, Überlagerungseffekte in der planaren Bildgebung oder durch eine nicht vollständig klinisch durchführbare Definition der Zielregion (z. B. Knochenmark) ergeben. Die 3D-Dosimetrie, unter Berücksichtigung zusätzlicher physikalischer oder biologischer Parameter (z. B. Dosisrate), kann in der Radionuklidtherapie einen wichtigen Beitrag zur Etablierung von Dosis-Wirkungsbeziehungen liefern, allerdings ist die klinisch-physiologische Interpretation der 3D-Dosisverteilungen derzeit noch stark limitiert durch Bildartefakte und Bildrauschen in den zur Dosimetrie eingesetzten SPECT-Bildern.

Abstract

Both, radioligand therapy (RLT) using radiolabelled PSMA-ligands (e. g. Lu-177-PSMA-617) and peptide receptor radionuclide therapy (PRRT) using radio-labelled somatostatin analogs (e. g. Lu-177-DOTATATE), evolved as promising therapy options for metastatic, castration-resistant prostate cancer and metastatic or inoperable neuroendocrine tumours. The theragnostic nuclide Lu-177 exhibits a therapy-relevant beta emission, accompanied by a Gamma emission, which can be directly used for quantitative imaging and dosimetry of the radiopharmaceutical distribution. The patient-specific 3D dosimetry based on quantitative Lu-177 imaging is the key to individualized therapy evaluation and planning for Lu-177-RLT and -PRRT, for which – so far – the clinical routine approach still mainly employs fixed activity schedules. However, reliable clinical dosimetry is demanding concerning both, the clinical workload during acquisition of patient-specific data for dosimetry and the technical, physical and clinical evaluation of the data. Furthermore, the strong inter-patient variability of the dose values and their dependence on the exact techniques used for dose evaluation complicate the finding of therapy-specific dose-effect-relationships. Especially the comparability of dose values between different clinical institutions requires a systematic and unified processing of dosimetry data, yet, at a reasonable clinical workload. The accuracy of current dose estimates is mainly limited due to the quality of the quantitative images. Further inaccuracies might be caused by – for example – an insufficient selection of measurement time points, motion artefacts, superposition artefacts during planar-based dosimetry, and an insufficient definition of the target regions (e. g. in case of bone marrow dosimetry). Three-dimensional dosimetry with consideration of radiobiological parameters (e. g. dose rate) can provide an important contribution to the finding of dose-effect-relationships, however, the clinical and physiological evaluation of currently reconstructed quantitative 3D activity distributions of SPECT images is still limited due to image artefacts and noise.

Schlüsselwörter

Radioligandentherapie - Peptid-Rezeptor-Radionuklidtherapie - Radionuklidtherapie - PSMA - DOTATATE - mCRPC - NET - Prostatakarzinom - neuroendokriner Tumor - Dosimetrie - Lu-177

Keywords

radioligand therapy - peptide receptor radionuclide therapy - radionuclide therapy - PSMA - DOTATATE - mCRPC - NET - prostate cancer - neuroendocrine tumour - dosimetry - Lu-177

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