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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2017 June;61(2):216-31

DOI: 10.23736/S1824-4785.16.02744-8

Copyright © 2015 EDIZIONI MINERVA MEDICA

language: English

Therapeutic schemes in 177Lu and 90Y-PRRT: radiobiological considerations

Anna SARNELLI 1, Francesco GUERRIERO 2, Francesca BOTTA 2, Mahila FERRARI 2, Lidia STRIGARI 3, Lisa BODEI 4, Vincenzo, D’ERRICO 1, Elisa GRASSI 5, Federica FIORONI 5, Giovanni PAGANELLI 6, Roberto ORECCHIA 7, 8, 9, Marta CREMONESI 2

1 Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy; 2 Medical Physics, European Institute of Oncology, Milan, Italy; 3 Laboratory of Medical Physics and Expert Systems, National Cancer Institute Regina Elena, Rome, Italy; 4 Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy; 5 Department of Medical Physics, Santa Maria Nuova Hospital, Reggio Emilia, Italy; 6 Nuclear Medicine Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Forlì-Cesena, Italy; 7 Scientific Direction and Department of Radiation Oncology, European Institute of Oncology, Milan, Italy; 8 Department of Health Sciences, Università degli Studi di Milano, Milan, Italy; 9 Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy


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BACKGROUND: The purpose of this work is to implement a radiobiological model to compare different treatment schedules for Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu and 90Y. The principal radiobiological quantities were studied as a function of radionuclides, fractionation schemes, activity distribution in kidneys and tumor radiosensitivity.
METHODS: Clinical data were used to derive representative absorbed doses for several treatment schemes for 177Lu-PRRT and for 90Y-PRRT and considered as input data for the radiobiological model. Both uniform and non-uniform activity distributions were considered for kidneys and cortex; for tumors a possible uptake reduction after each cycle and inter-patient radiosensitivity variability were investigated. Normal-Tissue-Complication-Probability (NTCP) and Tumor-Control-Probability (TCP) were evaluated.
RESULTS: Hyper-cycling has a limited advantage in terms of BED reduction on kidneys for 177Lu, while for 90Y the effect is sizable and helps in reducing the NTCP. For all 177Lu-schemes the renal toxicity risk is negligible while for some 90Y-schemes the NTCP is not null. In case of tumor uptake reduction with cycles the treatment efficacy is reduced with a BED loss up to 46%. The TCP decreases when assuming normally-distributed tumor radiosensitivity values.
CONCLUSIONS: This paper discusses how the combination of dosimetry and radiobiological modeling may help in exploring the link between the treatment schedule and the potential clinical outcome. The results highlight the capability of model to reproduce the available clinical data and provide useful qualitative information. Further investigation on dose distribution and dose uptake reduction with accurate clinical data is needed to progress in this field.


KEY WORDS: Nuclear medicine - Radiobiology - Dose fractionation - Treatment outcome

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