title: Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex.
  
  
  METHODS
  Planar and SPECT data were available for a patient examined with (111)In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., (111)In, (90)Y and (177)Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions.
  
  
  RESULTS
  Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for (90)Y and (177)Lu. Nevertheless, for (111)In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT.
  
  
  CONCLUSIONS
  The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.
authors.affiliation: Institute of Radiation Physics, Lausanne University Hospital, Lausanne, Switzerland. sebastien.baechler@chuv.ch
authors.forename: Sebastien
authors.initials: S
authors.lastname: Baechler
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hobbs
authors.forename: Ariane
authors.initials: A
authors.lastname: Boubaker
authors.forename: Franz
authors.initials: F
authors.lastname: Buchegger
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Eric C
authors.initials: EC
authors.lastname: Frey
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
mesh_terms: D000328:Adult; D006801:Humans; D007668:Kidney / Q000528:radiation effects*; D008297:Male; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D058958:Organs at Risk / Q000528:radiation effects; D011853:Radiobiology / Q000379:methods*; D011874:Radiometry; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000009:adverse effects* / Q000379:methods*; D018000:Receptors, Peptide / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D018000:Receptors, Peptide