title: Dosimetry in myeloablative (90)Y-labeled ibritumomab tiuxetan therapy: possibility of increasing administered activity on the base of biological effective dose evaluation. Preliminary results.
abstract: OBJECTIVE
  In our multicentric ongoing phase I activity escalation study, (90)Y-labeled ibritumomab tiuxetan (Ze-valin was administered in activity per kilo twice- and three times the maximum tolerable dose of 15 MBq/kg suggested for nonmyeloablative treatments by the U.S. registration study. The radioinduced myelodepression was overcome by stem cell autografting. The dosimetric aim was to correlate possible extramedullary toxicities to the organ-absorbed doses or to the biologic effective dose (BED). This is a conceptually more suitable parameter, as it takes into account not only the absorbed dose, but also the influence of the dose rate and of the tissue repair mechanism.
  
  
  METHODS
  Pretreatment planar dosimetry was performed on 16 patients with a median 200 MBq of (111)In-Zevalin. Conjugate view technique, background, attenuation, and partial scatter correction were adopted. Blood samples and a planar whole body scintigram were collected at least at 0.5, 48, 96, and 120 hours. Individual organ mass correction was based on a computed tomography scan. Internal dose calculation was performed by the OLINDA/EXM software. One (1) week after dosimetry, 12 patients were treated with 30 MBq/kg and 4 patients with 45 MBq/kg of (90)Y-Zevalin.
  
  
  RESULTS
  The absorbed dose per unit activity (Gy/GBq) were (median and range of 16 dosimetric studies): heart wall 3.8 [0.5, 9.7]; kidneys 4.9 [2.8, 10.5]; liver 5.5 [3.9, 8.9]; lungs 2.8 [0.4, 6.8]; red marrow 1.1 [0.8, 2.1]; spleen 6.3 [1.5, 10.9]; and testes 4.6 [3.0, 16.7]. The absorbed dose (Gy) for the 4 patients administered with 45 MBq/kg were (median and range): heart wall 17.6 [9.4, 25.1]; kidneys 16.3 [7.9, 20.3]; liver 20.9 [15.4, 24.3]; lungs 7.7 [5.6, 11.4]; red marrow 3.0 [2.4, 3.3]; spleen 28.4 [18.9, 30.8]; and testes 16.5 [12.2, 17.3]. No extramedullary toxicity was observed.
  
  
  CONCLUSIONS
  The administration of 45 MBq/kg of (90)Y ibritumomab tiuxetan to 4 patients with stem cell autografting was free from extramedullary toxicity. This is in agreement with both organ doses and BEDs below the corresponding toxicity thresholds. For these clinical and dosimetric reasons, a further increase in injectable activity could have been conceivable. If the more appropriate BED parameter were chosen for toxicity limit calculations, a wider margin of increase would have been possible. Our theoretical investigation demonstrates that, in this particular case of (90)Y Zevalin therapy, the uncertainty about radiobiological parameters was not a limiting factor for a BED-based calculation of the maximum injectable activity.
authors.affiliation: Nuclear Medicine, National Cancer Institute, Milan, Italy. carlo.chiesa@istitutotumori.mi.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Chiesa
authors.forename: Francesca
authors.initials: F
authors.lastname: Botta
authors.forename: Erika
authors.initials: E
authors.lastname: Di Betta
authors.forename: Angela
authors.initials: A
authors.lastname: Coliva
authors.forename: Marco
authors.initials: M
authors.lastname: Maccauro
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aliberti
authors.forename: Sergio
authors.initials: S
authors.lastname: Bavusi
authors.forename: Liliana
authors.initials: L
authors.lastname: Devizzi
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Ettore
authors.initials: E
authors.lastname: Seregni
authors.forename: Alessandro Massimo
authors.initials: AM
authors.lastname: Gianni
authors.forename: Emilio
authors.initials: E
authors.lastname: Bombardieri
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D019653:Myeloablative Agonists; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan