title: Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment.
abstract: The organs at risk in radionuclide therapy with (177)Lu-octreotate are the bone marrow and the kidneys. The primary aim of this study was to develop an individualized dosimetry protocol for the bone marrow. The secondary aim was to identify those patients, undergoing fractionated therapy with 7.4 GBq/cycle, who first reached an accumulated dose of either 2 Gy to the bone marrow or 23 Gy to the kidneys.
  
  
  METHODS
  Two hundred patients with metastatic neuroendocrine tumors with high somatostatin receptor expression were included. After the administration of 7.4 GBq of (177)Lu-octreotate, blood samples were drawn 6 times within the first 24 h. In 50 patients, additional blood samples were obtained at 96 and 168 h. Moreover, urine was collected from 30 patients during the first 24 h. Planar whole-body and SPECT/CT images over the abdomen were acquired at 24, 96, and 168 h after the infusion. Calculation of the absorbed radiation dose to the bone marrow was based on blood and urinary activity curves combined with organ-based analysis of the whole-body images. The absorbed dose to the kidney was calculated from the pharmacokinetic data obtained from SPECT/CT.
  
  
  RESULTS
  For a single cycle of 7.4 GBq, the absorbed dose to the bone marrow and the kidney ranged from 0.05 to 0.4 Gy and from 2 to 10 Gy, respectively. In 197 of 200 patients, the kidneys accumulated an absorbed dose of 23 Gy before the bone marrow reached 2 Gy. Between 2 and 10 cycles of (177)Lu-octreotate could be administered before the upper dose limit for the individual patient was reached.
  
  
  CONCLUSIONS
  A method based on repeated whole-body imaging in combination with blood and urinary activity data over time was developed to determine the absorbed dose to the bone marrow. The dose-limiting organ was the kidney in 197 of 200 patients. In 50% of the patients, more than 4 cycles of 7.4 GBq of (177)Lu-octreotate could be administered, whereas 20% of the subjects were treated with fewer than 4 cycles. Individualized absorbed dose calculation is essential to optimize the therapy.
authors.affiliation: Section of Medical Physics, Department of Radiology, Oncology, and Radiation Science, Uppsala University Hospital, Uppsala University, Uppsala, Sweden. mattias.sandstrom@akademiska.se
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.forename: Ulrike
authors.initials: U
authors.lastname: Garske-Román
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
authors.forename: Silvia
authors.initials: S
authors.lastname: Johansson
authors.forename: Charles
authors.initials: C
authors.lastname: Widström
authors.forename: Barbro
authors.initials: B
authors.lastname: Eriksson
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
mesh_terms: D001853:Bone Marrow / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007668:Kidney / Q000528:radiation effects*; D007700:Kinetics; D008297:Male; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D058958:Organs at Risk / Q000528:radiation effects*; D057285:Precision Medicine; D011874:Radiometry
chemical_list: D009942:Organometallic Compounds; C447941:lutetium Lu 177 dotatate; D015282:Octreotide