CoChat
Sign Up
Cited by 67Neuroblastoma Research and TreatmentsRadiopharmaceutical Chemistry and ApplicationsNeuroendocrine Tumor Research Advances

Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Open access
Matthay, Katherine K., Weiss, Brian, Villablanca, Judith G., Maris, John M., Yanik, Gregory A., DuBois, Steven G., Stubbs, James, Groshen, Susan +11 more·2012·Journal of Nuclear Medicine
DOI 10.2967/jnumed.111.098624PMC PMC12507347
Open this paper in CoChat — free accountOpen PDF

Abstract

UNLABELLED: (131)I-metaiodobenzylguanidine (MIBG) is specifically taken up in neuroblastoma, with a response rate of 20%-37% in relapsed disease. Nonradioactive carrier MIBG molecules inhibit uptake of (131)I-MIBG, theoretically resulting in less tumor radiation and increased risk of cardiovascular toxicity. Our aim was to establish the maximum tolerated dose of no-carrier-added (NCA) (131)I-MIBG, with secondary aims of assessing tumor and organ dosimetry and overall response. METHODS: Eligible patients were 1-30 y old with resistant neuroblastoma, (131)I-MIBG uptake, and cryopreserved hematopoietic stem cells. A diagnostic dose of NCA (131)I-MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. The treatment dose of NCA (131)I-MIBG (specific activity, 165 MBq/μg) was adjusted as necessary on the basis of critical organ tolerance limits. Autologous hematopoietic stem cells were infused 14 d after therapy to abrogate prolonged myelosuppression. Response and toxicity were evaluated on day 60. The NCA (131)I-MIBG was escalated from 444 to 777 MBq/kg (12-21 mCi/kg) using a 3 + 3 design. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/μL within 28 d or platelets to greater than 20,000/μL within 56 d, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. RESULTS: Three patients each were evaluable at 444, 555, and 666 MBq/kg without DLT. The dose of 777 MBq/kg dose was not feasible because of organ dosimetry limits; however, 3 assigned patients were evaluable for a received dose of 666 MBq/kg, providing a total of 6 patients evaluable for toxicity at 666 MBq/kg without DLT. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight patients had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. Four of 15 patients had a complete (n = 1) or partial (n = 3) response, 1 had a mixed response, 4 had stable disease, and 6 had progressive disease. CONCLUSION: NCA (131)I-MIBG with autologous peripheral blood stem cell transplantation is feasible at 666 MBq/kg without significant nonhematologic toxicity and with promising activity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2967/jnumed.111.098624

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Doses up to 30 Gy to the liver have resulted in less than 10% incidence of transient reversible hepatotoxicity.

    “but doses up to 30 Gy to the liver have resulted in less than 10% incidence of transient reversible hepatoxicity ( 52 , 53 ).”

    From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [53]

    The Methods (Toxicity Evaluation; page unavailable) define reversible hepatic enzyme elevation as a possible toxicity, and the Results (Dose Escalation and Toxicity; page unavailable) report no dose-limiting toxicity among evaluable patients. Neither passage establishes a liver dose of up to 30 Gy or a less-than-10% incidence of transient hepatotoxicity; searches for those terms found no such result in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Matthay, K. K., Weiss, B., Villablanca, J. G., Maris, J. M., Yanik, G. A., DuBois, S. G., Stubbs, J., Groshen, S., Tsao-Wei, D., Hawkins, R., Jackson, H., Goodarzian, F., Daldrup-Link, H., Panigrahy, A., Towbin, A., Shimada, H., Barrett, J., LaFrance, N., & Babich, J.
Affiliations
  • University of California, San Francisco (US)
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Southern California (US)
  • University of Pennsylvania (US)
  • University of Michigan (US)
  • Children's Hospital Los Angeles (US)
  • Stanford Medicine (US)
  • University of Pittsburgh (US)
ORCID
Venue
Journal of Nuclear Medicine
Publisher
Society of Nuclear Medicine
Published
2012-06-14
Volume
53
Issue
7
Pages
1155-1163
ISSN
  • 0161-5505 (ISSN-L)
  • 2159-662X
DOI
10.2967/jnumed.111.098624
PMC
PMC12507347
OpenAlex
W2096506747
Cited by
67
References
25
Citations by year
2026: 3 · 2025: 3 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 1
FWCI
4.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Nuclear Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
National Cancer Institute (P01CA81403, P01CA081403, CA-81403)
Topics
  • Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Keywords
131I-MIBG, metaiodobenzylguanidine, neuroblastoma, relapsed or refractory neuroblastoma, maximum tolerated dose, dose-limiting toxicity, organ dosimetry, autologous hematopoietic stem cell rescue, myelosuppression, cardiotoxicity, tumor response, childhood cancer
MeSH terms
Adolescent, Adult, Brain Neoplasms, Chemistry, Pharmaceutical, Child, Child, Preschool, Dose-Response Relationship, Radiation, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Neoplasm Recurrence, Local, Neuroblastoma, Quality of Life, Radiation Dosage, Radiometry, Software, Tissue Distribution, Tomography, X-Ray Computed, Hematopoietic Stem Cell Transplantation, Drug Resistance, Neoplasm, Radiopharmaceuticals, 3-Iodobenzylguanidine, Maximum Tolerated Dose, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review