title: Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients.
abstract: OBJECTIVE
  Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of (211)At-MX35 F(ab')2.
  
  
  METHODS
  Patients in clinical remission after salvage chemotherapy for peritoneal recurrence of ovarian cancer underwent i.p. infusion of (211)At-MX35 F(ab')2. Potassium perchlorate was given to block unwanted accumulation of (211)At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution.
  
  
  RESULTS
  The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose.
  
  
  CONCLUSIONS
  Intraperitoneal (211)At-MX35 F(ab')2 treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective dose potentially corresponds to a risk of treatment-induced carcinogenesis, optimization may still be valuable.
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Cederkrantz
authors.affiliation: Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Andersson
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.affiliation: Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Jacobsson
authors.affiliation: PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
authors.affiliation: Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Ljungberg
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Magnander
authors.affiliation: Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Stig
authors.initials: S
authors.lastname: Palm
authors.affiliation: Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: per.albertsson@oncology.gu.se.
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001246:Astatine / Q000493:pharmacokinetics*; D004583:Electrons / Q000627:therapeutic use; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010534:Peritoneal Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D061766:Proton Therapy; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D018570:Risk Assessment; D013270:Stomach / Q000000981:diagnostic imaging; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D001246:Astatine