Evidence map›Paper›PMID 20716957›Full record

ArticlemAbs

Targeting HER2: a report on the in vitro and in vivo pre-clinical data supporting trastuzumab as a radioimmunoconjugate for clinical trials.

Diane E Milenic, Karen J Wong, Kwamena E Baidoo, Tapan K Nayak, Celeste A S Regino, Kayhan Garmestani, Martin W Brechbiel

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
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  7. Preclinical Evaluation ofInternational journal of molecular sciences · 2021
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  8. First-in-human phase 0 study ofJournal of translational science · 2019
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  9. Review
  10. Review
  11. Article
  12. Exploration of a F(ab')Cancer biotherapy & radiopharmaceuticals · 2018
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Diane E MilenicRadioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. dm71q@nih.gov
Karen J Wong
Kwamena E Baidoo
Tapan K Nayak
Celeste A S Regino
Kayhan Garmestani
Martin W Brechbiel
National Institutes of Health · USCenter for Cancer Research · USNational Cancer Institute · US

Funding

Metal Chelate Conjugated Monoclonal Antibodies for Tumor Diagnosis and TherapyZIASC006353 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI BRECHBIEL, MARTIN W · 2009 to 2017
$9.4M
RESEARCH RESOURCE IN RADIONUCLIDE RESEARCHR24CA086307 · NCI · WASHINGTON UNIVERSITY · PI WELCH, MICHAEL J. · 1999 to 2009
$8.4M
Intramural NIH HHSNCI NIH HHS R24 CA086307NCI NIH HHS R24 CA86307
6 · The paper itself

Abstract

The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A"-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian, and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models, and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts, was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected, but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.

Indexed as

Xenograft Model Antitumor AssaysAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCell Line, TumorClinical Trials as TopicColonic NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHT29 CellsHumansImmunoconjugatesIndium RadioisotopesInjections, IntraperitonealInjections, IntravenousAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsErb-b2 Receptor Tyrosine KinasesImmunoconjugatesIndium RadioisotopesIsothiocyanatesN-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acidPentetic AcidTrastuzumab

Identifiers

PMID20716957
PMCPMC2958576
OpenAlexW2030994818

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.