Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning

  • Marta Cremonesi
  • Mahila Esmeralda Ferrari
  • Lisa Bodei
  • Carlo Chiesa
  • Anna Sarnelli
  • Cristina Garibaldi
  • Massimiliano Pacilio
  • Lidia Strigari
  • Paul Eugene Summers
  • Roberto Orecchia
  • Chiara Maria GranaEmail author
  • Francesca Botta
Review Article



Peptide receptor radionuclide therapy (PRRT) with 90Y-labelled and 177Lu-labelled peptides is an effective strategy for the treatment of metastatic/nonresectable neuroendocrine tumours (NETs). Dosimetry provides important information useful for optimizing PRRT with individualized regimens to reduce toxicity and increase tumour responses. However, this strategy is not applied in routine clinical practice, despite the fact that several dosimetric studies have demonstrated significant dose–effect correlations for normal organ toxicity and tumour response that can better guide therapy planning. The present study reviews the key relationships and the radiobiological models available in the literature with the aim of providing evidence that optimization of PRRT is feasible through the implementation of dosimetry.


The MEDLINE database was searched combining specific keywords. Original studies published in the English language reporting dose–effect outcomes in patients treated with PRRT were chosen.


Nine of 126 studies were selected from PubMed, and a further five were added manually, reporting on 590 patients. The studies were analysed and are discussed in terms of weak and strong elements of correlations.


Several studies provided evidence of clinical benefit from the implementation of dosimetry in PRRT, indicating the potential contribution of this approach to reducing severe toxicity and/or reducing undertreatment that commonly occurs. Prospective trials, possibly multicentre, with larger numbers of patients undergoing quantitative dosimetry and with standardized methodologies should be carried out to definitively provide robust predictive paradigms to establish effective tailored PRRT.


Peptide receptor radionuclide therapy (PRRT) Dosimetry Absorbed dose correlations Dose–effect Dose–toxicity 


Compliance with ethical standards

Conflicts of interest

L.B. acted as a consultant for Advanced Accelerator Applications (AAA) and Ipsen, and has received speaker honorarium from AAA, for work not related to the present paper.

C.C. was a consultant for Alfasigma and discloses funding from BTG Biocompatibles for work not related to the present paper.

M.P. was a consultant for Bayer Healthcare Pharmaceuticals Inc. as a member of the Targeted Alpha Therapy Working Group Advisory Board.

M.C., M.E.F., A.S., C.G., L.S., P.E.S., R.O., C.M.G. and F.B. declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marta Cremonesi
    • 1
  • Mahila Esmeralda Ferrari
    • 1
  • Lisa Bodei
    • 2
  • Carlo Chiesa
    • 3
  • Anna Sarnelli
    • 4
  • Cristina Garibaldi
    • 1
  • Massimiliano Pacilio
    • 5
  • Lidia Strigari
    • 6
  • Paul Eugene Summers
    • 1
  • Roberto Orecchia
    • 1
  • Chiara Maria Grana
    • 1
    Email author
  • Francesca Botta
    • 1
  1. 1.Istituto Europeo di OncologiaMilanoItaly
  2. 2.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Istituto Nazionale di TumoriMilanoItaly
  4. 4.Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)MeldolaItaly
  5. 5.Policlinico Umberto I, University HospitalRomaItaly
  6. 6.Istituto Nazionale dei Tumori Regina ElenaRomaItaly

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