title: Personalized177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: a simulation study.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) with177Lu-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-IA177Lu-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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Radiology and Nuclear Medicine, and Cancer Research Center, Université Laval, Quebec City, Canada.|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.
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.affiliation: Department of Radiology and Nuclear Medicine, and Cancer Research Center, Université Laval, Quebec City, Canada.|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.
authors.forename: François-Alexandre
authors.initials: FA
authors.lastname: Buteau
authors.affiliation: Department of Radiology and Nuclear Medicine, and Cancer Research Center, Université Laval, Quebec City, Canada. jean-mathieu.beauregard@chuq.qc.ca.|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.
authors.forename: Jean-Mathieu
authors.identifier: http://orcid.org/0000-0003-2123-145X
authors.initials: JM
authors.lastname: Beauregard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods*; D018000:Receptors, Peptide / Q000378:metabolism*; D012189:Retrospective Studies; D012449:Safety
chemical_list: C554548:177Lu-octreotate; D018000:Receptors, Peptide; D015282:Octreotide
keywords: 177Lu-octreotate; Dosimetry; Neuroendocrine tumours; Peptide receptor radionuclide therapy; Personalized