Skip to main content
Top
Published in:

Open Access 01-12-2024 | Original research

Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study

Authors: Rachele Danieli, Magdalena Mileva, Gwennaëlle Marin, Paulus Kristanto, Wendy Delbart, Bruno Vanderlinden, Zéna Wimana, Alain Hendlisz, Hugo Levillain, Nick Reynaert, Patrick Flamen, Ioannis Karfis

Published in: EJNMMI Research | Issue 1/2024

Login to get access

Abstract

Background

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs. Data from 37 patients enrolled in a prospective phase II study (LuMEn) were analysed. Treatment consisted of four cycles of [177Lu]Lu-DOTA-TATE administered 8–12 weeks apart. Three-time-point SPECT/CT imaging was performed after each treatment cycle, and dosimetry of tumours and organs-at-risk (kidneys and red marrow) was conducted following the medical internal radiation dose formalism. Coefficients of variation (CoV) assessed the variability of absorbed doses, activity concentrations on day 1, and effective half-lives. Linear mixed effect models (SAS software) were used to investigate the evolution of the dosimetric parameters over cycles, discerning between different primary NET types and grades of tumours.

Results

There is an important variability in absorbed doses and activity concentrations among patients, particularly in tumours (CoV: ~50%). Tumour absorbed doses and activity concentrations decreased over treatment cycles in pancreatic NETs, although at a limited rate (~-13%/cycle). An opposite trend was observed for the kidneys ( ~ + 8%/cycle). Effective half-lives remained relatively constant across cycles for both organs-at-risk and tumours. The primary NET type significantly influenced effective half-lives in tumours, shorter in pancreatic NETs than intestinal NETs (77 h vs. 107 h, p < 0.0001). No significant effect of the grade was observed on either of the variables investigated.

Conclusions

Our study revealed considerable variations in tumour absorbed doses among patients with NETs treated with a standardized protocol. These findings confirm the need for personalized dosimetry approaches in PRRT, considering patient and tumour characteristics.

Trial registration

EudraCT Number: 2012-003666-41. Clinicaltrials.gov identifier: NCT01842165. Registered 25 April 2013, https://​clinicaltrials.​gov/​ct2/​show/​NCT01842165.
Appendix
Available only for authorised users
Literature
4.
go back to reference Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL, et al. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high–dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403:2807–17. https://doi.org/10.1016/S0140-6736(24)00701-3.CrossRefPubMed Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL, et al. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high–dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403:2807–17. https://​doi.​org/​10.​1016/​S0140-6736(24)00701-3.CrossRefPubMed
5.
8.
go back to reference Maccauro M, Cuomo M, Bauckneht M, Bagnalasta M, Mazzaglia S, Scalorbi F, et al. The LUTADOSE trial: tumour dosimetry after the first administration predicts progression free survival in gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) patients treated with [177Lu]Lu-DOTATATE. Eur J Nucl Med Mol Imaging. 2024. https://doi.org/10.1007/s00259-024-06863-y.CrossRefPubMed Maccauro M, Cuomo M, Bauckneht M, Bagnalasta M, Mazzaglia S, Scalorbi F, et al. The LUTADOSE trial: tumour dosimetry after the first administration predicts progression free survival in gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) patients treated with [177Lu]Lu-DOTATATE. Eur J Nucl Med Mol Imaging. 2024. https://​doi.​org/​10.​1007/​s00259-024-06863-y.CrossRefPubMed
11.
go back to reference Garske-Roman U, Sandstrom M, Fross Baron K, Lundin L, Hellman P, Welin S, et al. Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018;45:970–88. https://doi.org/10.1007/s00259-018-3945-z.CrossRefPubMedPubMedCentral Garske-Roman U, Sandstrom M, Fross Baron K, Lundin L, Hellman P, Welin S, et al. Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018;45:970–88. https://​doi.​org/​10.​1007/​s00259-018-3945-z.CrossRefPubMedPubMedCentral
14.
go back to reference Jahn U, Ilan E, Sandstrom M, Lubberink M, Garske-Roman U, Sundin A. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE; differences in tumor dosimetry, vascularity and lesion metrics in pancreatic and small intestinal neuroendocrine neoplasms. Cancers (Basel). 2021;13. https://doi.org/10.3390/cancers13050962. Jahn U, Ilan E, Sandstrom M, Lubberink M, Garske-Roman U, Sundin A. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE; differences in tumor dosimetry, vascularity and lesion metrics in pancreatic and small intestinal neuroendocrine neoplasms. Cancers (Basel). 2021;13. https://​doi.​org/​10.​3390/​cancers13050962.
17.
go back to reference Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–7.PubMed Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–7.PubMed
29.
go back to reference Froidevaux S, Hintermann E, Török M, Mäcke HR, Beglinger C, Eberle AN. Differential regulation of somatostatin receptor type 2 (sst 2) expression in AR4-2J tumor cells implanted into mice during octreotide treatment. Cancer Res. 1999;59:3652–7.PubMed Froidevaux S, Hintermann E, Török M, Mäcke HR, Beglinger C, Eberle AN. Differential regulation of somatostatin receptor type 2 (sst 2) expression in AR4-2J tumor cells implanted into mice during octreotide treatment. Cancer Res. 1999;59:3652–7.PubMed
30.
go back to reference Mansi R, Plas P, Vauquelin G, Fani M. Distinct in vitro binding profile of the somatostatin receptor subtype 2 antagonist [177Lu]Lu-OPS201 compared to the agonist [177Lu]Lu-DOTA-TATE. Pharmaceuticals (Basel). 2021;14. https://doi.org/10.3390/ph14121265. Mansi R, Plas P, Vauquelin G, Fani M. Distinct in vitro binding profile of the somatostatin receptor subtype 2 antagonist [177Lu]Lu-OPS201 compared to the agonist [177Lu]Lu-DOTA-TATE. Pharmaceuticals (Basel). 2021;14. https://​doi.​org/​10.​3390/​ph14121265.
Metadata
Title
Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study
Authors
Rachele Danieli
Magdalena Mileva
Gwennaëlle Marin
Paulus Kristanto
Wendy Delbart
Bruno Vanderlinden
Zéna Wimana
Alain Hendlisz
Hugo Levillain
Nick Reynaert
Patrick Flamen
Ioannis Karfis
Publication date
01-12-2024
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2024
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-024-01163-w