Michela Del Prete1,2, François-Alexandre Buteau1,2, Jean-Mathieu Beauregard3,4. 1. Department of Radiology and Nuclear Medicine, and Cancer Research Center, Université Laval, Quebec City, Canada. 2. Department of Medical Imaging, and Oncology Branch of Research Center, CHU de Québec - Université Laval, 11 côte du Palais, Quebec City (QC), G1R 2J6, Canada. 3. Department of Radiology and Nuclear Medicine, and Cancer Research Center, Université Laval, Quebec City, Canada. jean-mathieu.beauregard@chuq.qc.ca. 4. Department of Medical Imaging, and Oncology Branch of Research Center, CHU de Québec - Université Laval, 11 côte du Palais, Quebec City (QC), G1R 2J6, Canada. jean-mathieu.beauregard@chuq.qc.ca.
Abstract
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course. METHODS: Thirty-six patients underwent 122 fixed-IA 177Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6 ± 2.4 GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2 ± 5.5, 1.3 ± 0.8, and 114 ± 66 Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23 Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle. RESULTS: In the P-PRRT regime, cumulative IA could have been increased to 43.7 ± 16.5 GBq over four induction cycles (10.9 ± 5.0 GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5 ± 2.5, 1.63 ± 0.61, and 163.4 ± 85.9 Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68-2.64-fold; P = 0.0013). CONCLUSION: By standardizing the renal absorbed dose delivered during the induction course, P-PRRT has the potential to significantly increase tumour absorbed dose, thus to augment the therapeutic benefit while limiting toxicity.
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course. METHODS: Thirty-six patients underwent 122 fixed-IA 177Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6 ± 2.4 GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2 ± 5.5, 1.3 ± 0.8, and 114 ± 66 Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23 Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle. RESULTS: In the P-PRRT regime, cumulative IA could have been increased to 43.7 ± 16.5 GBq over four induction cycles (10.9 ± 5.0 GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5 ± 2.5, 1.63 ± 0.61, and 163.4 ± 85.9 Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68-2.64-fold; P = 0.0013). CONCLUSION: By standardizing the renal absorbed dose delivered during the induction course, P-PRRT has the potential to significantly increase tumour absorbed dose, thus to augment the therapeutic benefit while limiting toxicity.
Authors: M Cremonesi; M Ferrari; A Di Dia; F Botta; C De Cicco; L Bodei; G Paganelli Journal: Q J Nucl Med Mol Imaging Date: 2011-04 Impact factor: 2.346
Authors: D J Kwekkeboom; W H Bakker; P P Kooij; M W Konijnenberg; A Srinivasan; J L Erion; M A Schmidt; J L Bugaj; M de Jong; E P Krenning Journal: Eur J Nucl Med Date: 2001-09
Authors: Mattias Sandström; Ulrike Garske-Román; Dan Granberg; Silvia Johansson; Charles Widström; Barbro Eriksson; Anders Sundin; Hans Lundqvist; Mark Lubberink Journal: J Nucl Med Date: 2012-12-07 Impact factor: 10.057
Authors: Dik J Kwekkeboom; Wouter W de Herder; Boen L Kam; Casper H van Eijck; Martijn van Essen; Peter P Kooij; Richard A Feelders; Maarten O van Aken; Eric P Krenning Journal: J Clin Oncol Date: 2008-05-01 Impact factor: 44.544
Authors: Esther I van Vliet; Eric P Krenning; Jaap J Teunissen; Hendrik Bergsma; Boen L Kam; Dik J Kwekkeboom Journal: J Nucl Med Date: 2013-10 Impact factor: 10.057
Authors: Jean-Mathieu Beauregard; Michael S Hofman; Jucilene M Pereira; Peter Eu; Rodney J Hicks Journal: Cancer Imaging Date: 2011-06-15 Impact factor: 3.909
Authors: Johanna Svensson; Gertrud Berg; Bo Wängberg; Maria Larsson; Eva Forssell-Aronsson; Peter Bernhardt Journal: Eur J Nucl Med Mol Imaging Date: 2015-02-06 Impact factor: 9.236
Authors: F Guerriero; M E Ferrari; F Botta; F Fioroni; E Grassi; A Versari; A Sarnelli; M Pacilio; E Amato; L Strigari; L Bodei; G Paganelli; M Iori; G Pedroli; M Cremonesi Journal: Biomed Res Int Date: 2013-06-20 Impact factor: 3.411
Authors: Zhantong Wang; Orit Jacobson; Rui Tian; Ronnie C Mease; Dale O Kiesewetter; Gang Niu; Martin G Pomper; Xiaoyuan Chen Journal: Bioconjug Chem Date: 2018-06-15 Impact factor: 4.774