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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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Hallqvist, A, Bergmark, K, Bäck, T, Andersson, H, Dahm-Kähler, P, Johansson, M, Lindegren, S, Jensen, H, Jacobsson, L, Hultborn, R, Palm, S & Albertsson, P 2019, 'Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations', Journal of nuclear medicine : official publication, Society of Nuclear Medicine, bind 60, nr. 8, s. 1073-1079. https://doi.org/10.2967/jnumed.118.220384

APA

Hallqvist, A., Bergmark, K., Bäck, T., Andersson, H., Dahm-Kähler, P., Johansson, M., Lindegren, S., Jensen, H., Jacobsson, L., Hultborn, R., Palm, S., & Albertsson, P. (2019). Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 60(8), 1073-1079. https://doi.org/10.2967/jnumed.118.220384

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Author

Hallqvist, Andreas ; Bergmark, Karin ; Bäck, Tom ; Andersson, Håkan ; Dahm-Kähler, Pernilla ; Johansson, Mia ; Lindegren, Sture ; Jensen, Holger ; Jacobsson, Lars ; Hultborn, Ragnar ; Palm, Stig ; Albertsson, Per. / Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer : Long-Term Follow-up with Individual Absorbed Dose Estimations. I: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019 ; Bind 60, Nr. 8. s. 1073-1079.

Bibtex

@article{997872f629714f798f0e7169e7bed18f,
title = "Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations",
abstract = "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.",
author = "Andreas Hallqvist and Karin Bergmark and Tom B{\"a}ck and H{\aa}kan Andersson and Pernilla Dahm-K{\"a}hler and Mia Johansson and Sture Lindegren and Holger Jensen and Lars Jacobsson and Ragnar Hultborn and Stig Palm and Per Albertsson",
note = "{\textcopyright} 2019 by the Society of Nuclear Medicine and Molecular Imaging.",
year = "2019",
month = aug,
doi = "10.2967/jnumed.118.220384",
language = "English",
volume = "60",
pages = "1073--1079",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine",
number = "8",

}

RIS

TY - JOUR

T1 - Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer

T2 - Long-Term Follow-up with Individual Absorbed Dose Estimations

AU - Hallqvist, Andreas

AU - Bergmark, Karin

AU - Bäck, Tom

AU - Andersson, Håkan

AU - Dahm-Kähler, Pernilla

AU - Johansson, Mia

AU - Lindegren, Sture

AU - Jensen, Holger

AU - Jacobsson, Lars

AU - Hultborn, Ragnar

AU - Palm, Stig

AU - Albertsson, Per

N1 - © 2019 by the Society of Nuclear Medicine and Molecular Imaging.

PY - 2019/8

Y1 - 2019/8

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.

AB - 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.

U2 - 10.2967/jnumed.118.220384

DO - 10.2967/jnumed.118.220384

M3 - Journal article

C2 - 30683761

VL - 60

SP - 1073

EP - 1079

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 8

ER -

ID: 59320808