title: Therapeutic schemes in 177Lu and 90Y-PRRT: radiobiological considerations.
abstract: 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.
authors.affiliation: Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy - anna.sarnelli@irst.emr.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Sarnelli
authors.affiliation: Medical Physics, European Institute of Oncology, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerriero
authors.affiliation: Medical Physics, European Institute of Oncology, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Botta
authors.affiliation: Medical Physics, European Institute of Oncology, Milan, Italy.
authors.forename: Mahila
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Laboratory of Medical Physics and Expert Systems, National Cancer Institute Regina Elena, Rome, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
authors.affiliation: Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: D'Errico
authors.affiliation: Department of Medical Physics, Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Grassi
authors.affiliation: Department of Medical Physics, Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fioroni
authors.affiliation: Nuclear Medicine Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Forlì-Cesena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
authors.affiliation: Scientific Direction and Department of Radiation Oncology, European Institute of Oncology, Milan, Italy.|Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.|Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
authors.affiliation: Medical Physics, European Institute of Oncology, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cremonesi
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D006801:Humans; D007668:Kidney / Q000528:radiation effects; D008187:Lutetium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy; D058958:Organs at Risk; D011868:Radioisotopes / Q000627:therapeutic use*; D011874:Radiometry; D011878:Radiotherapy / Q000379:methods*; D018000:Receptors, Peptide / Q000378:metabolism*; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D011868:Radioisotopes; D018000:Receptors, Peptide; D015021:Yttrium Radioisotopes; D008187:Lutetium