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Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations

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  3. Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

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  1. Towards elucidating the radiochemistry of astatine - Behavior in chloroform

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  2. Multifunctional Clickable Reagents for Rapid Bioorthogonal Astatination and Radio-Crosslinking

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  3. Extraction of 211At from nitric acid solutions into various organic solvents for use as an α-source for radiation chemistry studies

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  • Andreas Hallqvist
  • Karin Bergmark
  • Tom Bäck
  • Håkan Andersson
  • Pernilla Dahm-Kähler
  • Mia Johansson
  • Sture Lindegren
  • Holger Jensen
  • Lars Jacobsson
  • Ragnar Hultborn
  • Stig Palm
  • Per Albertsson
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Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle-emitting 211At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using 211At conjugated to MX35, the antigen-binding fragments-F(ab')2-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of 211At-MX35 F(ab')2.Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.

Original languageEnglish
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume60
Issue number8
Pages (from-to)1073-1079
Number of pages7
ISSN0161-5505
DOIs
Publication statusPublished - Aug 2019

ID: 59320808