title: A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity.
abstract: BACKGROUND
  (﻿177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2 GBq (3.5-8.3 GBq) of (177)Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168 h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period.
  
  
  RESULTS
  The mean absorbed dose to the bone marrow was estimated to 0.20 Gy (0.11-0.37 Gy) per 7.4 GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p = 0.01), WBC (p < 0.01) and PLT (p < 0.01) counts. The total mean absorbed dose to the bone marrow was 0.64 Gy (0.30-1.5 Gy) per 24 GBq (8.2-37 GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p < 0.01), WBC (p = 0.01) and PLT (p < 0.01) counts.
  
  
  CONCLUSIONS
  The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling.
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden. johanna.svensson@oncology.gu.se.
authors.forename: Johanna
authors.identifier: http://orcid.org/0000-0002-5251-1713
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Department of Radiation Physics, Sahlgrenska University Hospital, Gothenburg, Sweden.|Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Rydén
authors.affiliation: Department of Radiation Physics, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Linn
authors.initials: L
authors.lastname: Hagmarker
authors.affiliation: Department of Radiation Physics, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Hemmingsson
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Wängberg
authors.affiliation: Department of Radiation Physics, Sahlgrenska University Hospital, Gothenburg, Sweden.|Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
keywords: 177Lu-DOTATATE; Dosimetry; Haematological toxicity; PRRT