Evidence map›Paper›PMID 25734548›Full record

ArticleRadiology2015

Development and Validation of an Immuno-PET Tracer as a Companion Diagnostic Agent for Antibody-Drug Conjugate Therapy to Target the CA6 Epitope.

Ohad Ilovich, Arutselvan Natarajan, Sharon Hori, Ataya Sathirachinda, Richard Kimura, Ananth Srinivasan, Mathias Gebauer, Jochen Kruip, Ingo Focken, Christian Lange and 5 more

Open access · greenAbstract readComparative StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Radiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  10. Review
  11. Imaging B Cells in a Mouse Model of Multiple Sclerosis UsingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017
    Article
  12. Article
  13. Article
  14. Antibody-Drug Conjugates: Possibilities and Challenges.Avicenna journal of medical biotechnology
    Review
  15. 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

15 authors at 4 institutions in 4 countries.

Ohad IlovichFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Arutselvan NatarajanFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Sharon HoriFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Ataya SathirachindaFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Richard KimuraFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Ananth SrinivasanFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Mathias GebauerFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Jochen KruipFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Ingo FockenFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Christian LangeFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Chantal CarrezFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Ingrid SassoonFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Veronique BlancFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Susanta K SarkarFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Sanjiv S GambhirFrom the Department of Radiology (O.I., A.N., S.H., A. Sathirachinda, R.K., A. Srinivasan, S.S.G.) and Departments of Bioengineering and Materials Science & Engineering (S.S.G.), Stanford University, 318 Campus Dr, Room E153, Stanford, CA 94305; Sanofi R&D, BioInnovation Novel Protein Therapeutics, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany (M.G., J.K., I.F., C.L.); Sanofi Oncology, Vitry, France (C.C., I.S., V.B.); and Sanofi Oncology, Cambridge, Mass (S.K.S.).
Stanford University · USSanofi (Germany) · DESanofi (France) · FRSanofi (Mexico) · MX

Funding

Small Animal ImagingP50CA114747 · NCI · STANFORD UNIVERSITY · PI RAO, JIANGHONG · 2005 to 2014
$18.2M
NCI NIH HHS P50 CA114747NCI NIH HHS P50CA114747
6 · The paper itself

Abstract

purposeTo develop and compare three copper 64 ((64)Cu)-labeled antibody fragments derived from a CA6-targeting antibody (huDS6) as immuno-positron emission tomography (immuno-PET)-based companion diagnostic agents for an antibody-drug conjugate by using huDS6. MATERIALS AND

methodsThree antibody fragments derived from huDS6 were produced, purified, conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and evaluated in the following ways: (a) the affinity of the fragments and the DOTA conjugates was measured via flow cytometry, (b) the stability of the labeled fragments was determined ex vivo in human serum over 24 hours, and (c) comparison of the in vivo imaging potential of the fragments was evaluated in mice bearing subcutaneous CA6-positive and CA6-negative xenografts by using serial PET imaging and biodistribution. Isotype controls with antilysozyme and anti-DM4 B-Fabs and blocking experiments with an excess of either B-Fab or huDS6 were used to determine the extent of the antibody fragment (64)Cu-DOTA-B-Fab binding specificity. Immunoreactivity and tracer kinetics were evaluated by using cellular uptake and 48-hour imaging experiments, respectively. Statistical analyses were performed by using t tests, one-way analysis of variance, and Wilcoxon and Mann-Whitney tests.

resultsThe antibody fragment (64)Cu-DOTA-B-Fab was more than 95% stable after 24 hours in human serum, had an immunoreactivity of more than 70%, and allowed differentiation between CA6-positive and CA6-negative tumors in vivo as early as 6 hours after injection, with a 1.7-fold uptake ratio between tumors. Isotype and blocking studies experiments showed tracer-specific uptake in antigen-positive tumors, despite some nonspecific uptake in both tumor models.

conclusionThree antibody fragments were produced and examined as potential companion diagnostic agents. (64)Cu-DOTA-B-Fab is a stable and effective immuno-PET tracer for CA6 imaging in vivo.

Indexed as

Copper RadioisotopesImmunoglobulin FragmentsAnimalsCells, CulturedDrug TherapyEpitopesHumansImmunologic TestsMicePositron-Emission TomographyRadioactive TracersCopper RadioisotopesEpitopesImmunoglobulin FragmentsRadioactive Tracers

Identifiers

PMID25734548
PMCPMC4570559
OpenAlexW2065823339

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.