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Cited by 57Radiopharmaceutical Chemistry and ApplicationsAdvanced Radiotherapy TechniquesEffects of Radiation Exposure

The clinical importance of dosimetry in radioimmunotherapy with tositumomab and iodine I 131 tositumomab

Wahl, Richard L.·2003·Seminars in Oncology
DOI 10.1053/sonc.2003.23799
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Abstract

Radioimmunotherapy (RIT) is a promising emerging therapy for non-Hodgkin's lymphoma and may ultimately prove useful in the treatment of other tumors. The most extensively investigated RIT agent is tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA, and GlaxoSmithKline, Philadelphia, PA) which has been administered to over 1,000 patients during the past 9 years. As with most drugs, there is considerable interpatient variability in the clearance rate (or total body residence time) of radioimmunoconjugates. The clearance rate of iodine I 131 tositumomab in clinical trials has varied by as much as five-fold. The advantage of RIT with iodine-131, which emits both gamma photons and beta particles, is that by scanning it allows for the determination of the patient-specific total body residence time by the administration of a trace-labeled dose of the radionuclide (ie, dosimetric dose). By administration of the dosimetric (trace-labeled) dose, and determination of the patient's residence time (a measure of how long the radionuclide is retained in the body), the therapeutic dose can be precisely adjusted to maximize the therapeutic effect and minimize toxicity. Tositumomab and iodine I 131 tositumomab is a specific therapeutic at two levels: first, it specifically targets the tumor, delivering a log or more radiation to tumor compared with the rest of the body; and second, the administered dose of radioactivity is patient-specific. The paradigm of a targeted drug with a patient-specific dose may become more routine as targeted therapies are further developed along with better assays to directly measure drug levels. For the present, whole-body dosimetry is routinely applied for RIT with tositumomab and iodine I 131 tositumomab and has proven to be a reliable method to determine the patient-specific maximally tolerated therapeutic radiation dose to maximize efficacy while minimizing organ and bone marrow toxicity.

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  • Patients lacking a spleen may have much slower clearance of radioantibody from the blood, and thus higher organ doses per administered activity than in patients with an intact spleen, as seen with anti-CD20 antibodies.

    “Similarly, patients lacking a spleen may have much slower clearance of radioantibody from the blood, and thus higher organ doses/administered activity than in patients with an intact spleen, this having been seen with anti-CD20 antibodies ( 16 ).”

    From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [16]

  • For 131I-antiCD20 antibodies, a whole-body absorbed dose of 75 cGy was established as the maximum-tolerated dose in patients with non-Hodgkin lymphoma who had been heavily pretreated with chemotherapy.

    “For 131 I-antiCD20 antibodies, a whole-body absorbed dose of 75 cGy was established as the maximum-tolerated dose (MTD) in patients with non-Hodgkin lymphoma who had been heavily pretreated with chemotherapy ( 16 ).”

    From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [16]

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Authors
Wahl, R. L.
Affiliations
Johns Hopkins University (US)
Corresponding author
Wahl, Richard L.
ORCID
Wahl, Richard L.
Venue
Seminars in Oncology
Publisher
Elsevier BV
Published
2003-04
Volume
30
Issue
2E
Pages
31-38
ISSN
0093-7754 (ISSN-L)
DOI
10.1053/sonc.2003.23799
OpenAlex
W4235206899
Cited by
57
References
0
Citations by year
2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 3 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
FWCI
3.31
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
Seminars in Oncology (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
radioimmunotherapy, tositumomab, iodine-131 tositumomab, Bexxar, whole-body dosimetry, individualized dosing, non-Hodgkin lymphoma, radionuclide clearance, beta and gamma radiation, myelosuppression, organ toxicity

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