Theranostic Intratumoral Convection-Enhanced Delivery of 124 I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry.

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  • Additional Information
    • Source:
      Publisher: Society of Nuclear Medicine Country of Publication: United States NLM ID: 0217410 Publication Model: Electronic Cited Medium: Internet ISSN: 1535-5667 (Electronic) Linking ISSN: 01615505 NLM ISO Abbreviation: J Nucl Med Subsets: MEDLINE
    • Publication Information:
      Publication: Reston, VA : Society of Nuclear Medicine
      Original Publication: [Chicago, Ill.] : S.N. Turiel & Assoc.
    • Subject Terms:
      Brain Stem Neoplasms*/diagnostic imaging ; Brain Stem Neoplasms*/radiotherapy ; Iodine Radioisotopes* ; Diffuse Intrinsic Pontine Glioma*/diagnostic imaging ; Diffuse Intrinsic Pontine Glioma*/radiotherapy ; Radiometry*; Humans ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Convection ; Positron Emission Tomography Computed Tomography ; Glioma/diagnostic imaging ; Glioma/radiotherapy ; Tissue Distribution ; Infant ; Young Adult
    • Abstract:
      Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124 I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124 I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124 I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124 I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124 I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124 I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.
      (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
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    • Grant Information:
      P30 CA008748 United States CA NCI NIH HHS
    • Contributed Indexing:
      Keywords: 124I-omburtamab; DIPG; convection-enhanced delivery; diffuse intrinsic pontine glioma; dosimetry; organ-absorbed doses
    • Accession Number:
      0 (Iodine Radioisotopes)
      0 (Iodine-124)
    • Publication Date:
      Date Created: 20240814 Date Completed: 20240903 Latest Revision: 20241102
    • Publication Date:
      20241102
    • Accession Number:
      PMC11372263
    • Accession Number:
      10.2967/jnumed.123.266365
    • Accession Number:
      39142829