TY - JOUR T1 - Intraperitoneal α-Emitting Radioimmunotherapy with <sup>211</sup>At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1073 LP - 1079 DO - 10.2967/jnumed.118.220384 VL - 60 IS - 8 AU - Andreas Hallqvist AU - Karin Bergmark AU - Tom Bäck AU - Håkan Andersson AU - Pernilla Dahm-Kähler AU - Mia Johansson AU - Sture Lindegren AU - Holger Jensen AU - Lars Jacobsson AU - Ragnar Hultborn AU - Stig Palm AU - Per Albertsson Y1 - 2019/08/01 UR - http://jnm.snmjournals.org/content/60/8/1073.abstract N2 - 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. ER -