title: High-dose radioimmunotherapy with 90Y-ibritumomab tiuxetan: comparative dosimetric study for tailored treatment.
abstract: High-dose (90)Y-ibritumomab tiuxetan therapy and associated autologous stem cell transplantation (ASCT) were applied after dosimetry. This paper reports dosimetric findings for 3 different methods, including image corrections and actual organ mass corrections. Our first goal was to identify the most reliable and feasible dosimetric method to be adopted in high-dose therapy with (90)Y-ibritumomab tiuxetan. The second goal was to verify the safety of the prescribed activity and the best timing of stem cell reinfusion.
  
  
  METHODS
  Twenty-two patients with refractory non-Hodgkin's lymphoma were enrolled into 3 activity groups escalating to 55.5 MBq/kg. A somewhat arbitrary cutoff of 20 Gy to organs (except red marrow) was defined as a safe limit for patient recruitment. ASCT was considered of low risk when the dose to reinfused stem cells was less than 50 mGy. (111)In-Ibritumomab tiuxetan (185 MBq) was administered for dosimetry. Blood samples were collected up to 130 h after injection to derive individual blood clearance rates and red marrow doses. Five whole-body images were acquired up to 7 d after injection. A transmission scan and a low-dose CT scan were also acquired. The conjugate-view technique was used, and images were corrected for background, scatter, and attenuation. Absorbed doses were calculated using the OLINDA/EXM software, adjusting doses for individual organ masses. The biodistribution data were analyzed for dosimetry by the conjugate-view technique using 3 methods. Method A was a patient-specific method applying background, scatter, and attenuation correction, with absorbed doses calculated using the OLINDA/EXM software and doses adjusted for individual organ masses and individually estimated blood volumes. Method B was a reference method using the organ masses of the reference man and woman phantoms. Method C was a simplified method using standard blood and red marrow volumes and no corrections.
  
  
  RESULTS
  The medians and ranges (in parentheses) for dose estimates (mGy/MBq) according to method A were 1.7 (0.3-3.5) for lungs, 2.8 (1.8-10.6) for liver, 1.7 (0.6-3.8) for kidneys, 1.9 (0.8-5.0) for spleen, 0.8 (0.4-1.0) for red marrow, and 2.8 (1.3-4.7) for testes. None of patients had to postpone ASCT. Absorbed doses from method B differed from method A by up to 100% for liver, 80% for kidneys, 335% for spleen, and 80% for blood because of differences between standard and actual masses. Compared with method A, method C led to dose overestimates of up to 4-fold for lungs, 2-fold for liver, 5-fold for kidneys, 7-fold for spleen, 2-fold for red marrow, and 2-fold for testes.
  
  
  CONCLUSIONS
  Patient-specific dosimetry with image correction and mass adjustment is recommended in high-dose (90)Y-ibritumomab tiuxetan therapy, for which liver is the dose-limiting organ. Overly simplified dosimetry may provide inaccurate information on the dose to critical organs, the recommended values of administered activity, and the timing of ASCT.
authors.affiliation: Division of Medical Physics, European Institute of Oncology, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cremonesi
authors.forename: Mahila
authors.initials: M
authors.lastname: Ferrari
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Grana
authors.forename: Anna
authors.initials: A
authors.lastname: Vanazzi
authors.forename: Mike
authors.initials: M
authors.lastname: Stabin
authors.forename: Mirco
authors.initials: M
authors.lastname: Bartolomei
authors.forename: Stefano
authors.initials: S
authors.lastname: Papi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Prisco
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Ferrucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan