Nuclear Medicine and Biology

2006

DOI: 10.1016/j.nucmedbio.2006.07.009

|View full text |Cite

|

Sign up to set email alerts

|

Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab′)2: therapeutic efficacy and myelotoxicity

Jörgen Elgqvist

¹

,

²

,

³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Effect Of Dose-rate and Fractionation1

Introduction1

Discussion1

Alpha-therapy Of Cancers With 211 At-labeled Targeting Agents1

Citation Types

Supporting

2

Mentioning

19

Contrasting

0

Year Published

2007

2007

2022

2022

Publication Types

Select...

Article9

Other1

Relationship

Self Cite2

Independent8

Authors

Journals

Cited by 30 publications

(21 citation statements)

References 24 publications

Supporting

2

Mentioning

19

Contrasting

0

Order By: Relevance

“…Few studies have investigated fractionation of internal alpha particle radiation on tumor and normal tissue RBE in vivo or in vitro. Barendsen et al At labeled MX35 F(ab') 2 compared to single administration [81]. Another important aspect of antibody delivered alpha-emitter that needs to be taken into consideration is the possible saturation and turnover rate of tumor antigens during fractionated doses of radiolabeled antibodies that could reduce fractionated doses.…”

Section: Effect Of Dose-rate and Fractionationmentioning

confidence: 99%

Alpha Particle Emitter Radiolabeled Antibody for Metastatic Cancer: What Can We Learn from Heavy Ion Beam Radiobiology?

Song¹,

Senthamizhchelvan²,

et al. 2012

View full text Add to dashboard Cite

Alpha-particle emitter labeled monoclonal antibodies are being actively developed for treatment of metastatic cancer due to the high linear energy transfer (LET) and the resulting greater biological efficacy of alpha-emitters. Our knowledge of high LET particle radiobiology derives primarily from accelerated heavy ion beam studies. In heavy ion beam therapy of loco-regional tumors, the modulation of steep transition to very high LET peak as the particle approaches the end of its track (known as the Bragg peak) enables greater delivery of biologically potent radiation to the deep seated tumors while sparing normal tissues surrounding the tumor with the relatively low LET track segment part of the heavy ion beam. Moreover, fractionation of the heavy ion beam can further enhance the peak-to-plateau relative biological effectiveness (RBE) ratio. In contrast, internally delivered alpha particle radiopharmaceutical therapy lack the control of Bragg peak energy deposition and the dose rate is determined by the administered activity, alpha-emitter half-life and biological kinetics of the radiopharmaceutical. The therapeutic ratio of tumor to normal tissue is mainly achieved by tumor specific targeting of the carrier antibody. In this brief overview, we review the radiobiology of high LET radiations learned from ion beam studies and identify the features that are also applicable for the development of alpha-emitter labeled antibodies. The molecular mechanisms underlying DNA double strand break repair response to high LET radiation are also discussed.

“…Few studies have investigated fractionation of internal alpha particle radiation on tumor and normal tissue RBE in vivo or in vitro. Barendsen et al At labeled MX35 F(ab') 2 compared to single administration [81]. Another important aspect of antibody delivered alpha-emitter that needs to be taken into consideration is the possible saturation and turnover rate of tumor antigens during fractionated doses of radiolabeled antibodies that could reduce fractionated doses.…”

Section: Effect Of Dose-rate and Fractionationmentioning

confidence: 99%

Alpha Particle Emitter Radiolabeled Antibody for Metastatic Cancer: What Can We Learn from Heavy Ion Beam Radiobiology?

Song¹,

Senthamizhchelvan²,

et al. 2012

View full text Add to dashboard Cite

Alpha-particle emitter labeled monoclonal antibodies are being actively developed for treatment of metastatic cancer due to the high linear energy transfer (LET) and the resulting greater biological efficacy of alpha-emitters. Our knowledge of high LET particle radiobiology derives primarily from accelerated heavy ion beam studies. In heavy ion beam therapy of loco-regional tumors, the modulation of steep transition to very high LET peak as the particle approaches the end of its track (known as the Bragg peak) enables greater delivery of biologically potent radiation to the deep seated tumors while sparing normal tissues surrounding the tumor with the relatively low LET track segment part of the heavy ion beam. Moreover, fractionation of the heavy ion beam can further enhance the peak-to-plateau relative biological effectiveness (RBE) ratio. In contrast, internally delivered alpha particle radiopharmaceutical therapy lack the control of Bragg peak energy deposition and the dose rate is determined by the administered activity, alpha-emitter half-life and biological kinetics of the radiopharmaceutical. The therapeutic ratio of tumor to normal tissue is mainly achieved by tumor specific targeting of the carrier antibody. In this brief overview, we review the radiobiology of high LET radiations learned from ion beam studies and identify the features that are also applicable for the development of alpha-emitter labeled antibodies. The molecular mechanisms underlying DNA double strand break repair response to high LET radiation are also discussed.

“…Pre-clinical studies have shown the therapeutic efficacy of TAT against i.p. ovarian cancer [2][3][4]. Specifically, treatment with the monoclonal antibody fragment MX35 F(ab') 2 , labelled with the alpha-particle emitter astatine-211 ( 211 At, t ½ = 7.2 h) was shown to be sterilizing for tumors less than approximately 0.5 mm in diameter, without bringing about absorbed doses that were critical to normal tissues [5].…”

Section: Introductionmentioning

confidence: 99%

Absorbed Doses and Risk Estimates of 211At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

¹

,

²

,

³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

Self Cite

View full text Add to dashboard Cite

No abstract

“…As the range of the emitted particles conforms to the size of the target cluster, a high fraction of emitted energy will be absorbed in the target. The therapeutic potential of the a-emitter 211 At (T 1/2 5 7.21 h) labeled to MOv18, MX35, and trastuzumab has been demonstrated in studies using a preclinical mouse ovarian cancer model (2)(3)(4)(5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab′)₂—A Phase I Study

et al. 2009

Self Cite

View full text Add to dashboard Cite

The a-emitter 211 At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. Methods: Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. 211 At was labeled to MX35 F(ab9) 2 using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with 211 At-MX35 F(ab9) 2 (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. g-camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. Results: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% 6 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 6 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 6 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 6 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 6 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 6 1.6 mGy/(MBq/L) (mean 6 SD). No adverse effects were observed either subjectively or in laboratory parameters. Conclusion: This study indicates that by intraperitoneal administration of 211 At-MX35 F(ab9) 2 it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity. The lifetime risk of ovarian cancer is 1%22% in European and U.S. women. Despite seemingly successful cytoreductive surgery, followed by systemic chemotherapy, most patients will relapse and succumb. The relapse is most frequently localized in the abdominal cavity. New systemic chemotherapy regimens have not improved the outcome over the past decade, which prompted experimental intraperitoneal treatments, including radioimmunotherapy.Radioimmunotherapy with b-emitters has displayed promising results, although an international randomized phase III study of 90 Y-HMFG1 showed no improvement in survival or time to relapse (1). This disappointing result could be partly explained by the choice of radionuclide. The long range of this b-emitter results in poor irradiation of small tumor clusters, likely insufficient to eradicate peritoneal micrometastases. Furthermore, the relativel...

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.