Evidence map›Paper›PMID 26596724›Full record

ArticleEuropean journal of nuclear medicine and molecular imaging2016

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity ⁸⁶Y- or ¹⁷⁷Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates.

Sarah M Cheal, Hong Xu, Hong-Fen Guo, Sang-Gyu Lee, Blesida Punzalan, Sandhya Chalasani, Edward K Fung, Achim Jungbluth, Pat B Zanzonico, Jorge A Carrasquillo and 5 more

Open access · greenAbstract read
In one paragraph

Article in European journal of nuclear medicine and molecular imaging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 49 citations in OpenAlex.

  1. Establishment ofMolecular pharmaceutics · 2026
    Article
  2. PreclinicalJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
    Article
  3. Article
  4. PretargetedTheranostics · 2026
    Article
  5. Article
  6. Article
  7. Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a BivalentJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
    Article
  8. Efficacy of HER2-Targeted IntraperitonealJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023
    Article
  9. Clearing and Masking Agents in Pretargeting Strategies.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  10. Article
  11. Article
  12. Pretargeting: A Path Forward for Radioimmunotherapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Review
  13. Article
  14. Article
  15. Glypican-3 targeted delivery ofScientific reports · 2021
    Article
  16. A Self-Assembling and Disassembling (SADA) Bispecific Antibody (BsAb) Platform for Curative Two-step Pretargeted Radioimmunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  17. Review
  18. Review
  19. AnBioconjugate chemistry · 2020
    Article
  20. Alpha radioimmunotherapy usingTheranostics · 2020
    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 3 institutions in 1 country.

Sarah M ChealDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hong XuDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hong-Fen GuoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sang-Gyu LeeDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Blesida PunzalanDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sandhya ChalasaniDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Edward K FungMolecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 415 E. 68th Street, Z-2064, New York, NY, 10065, USA.
Achim JungbluthDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Pat B ZanzonicoDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jorge A CarrasquilloDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Joseph O'DonoghueDepartment of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Peter M Smith-JonesDepartment of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, NY, USA.
K Dane WittrupDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nai-Kong V CheungMolecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 415 E. 68th Street, Z-2064, New York, NY, 10065, USA.
Steven M LarsonDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. larsons@mskcc.org.
Memorial Sloan Kettering Cancer Center · USMassachusetts Institute of Technology · USStony Brook University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
SPORE In Prostate CancerP50CA092629 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Yu Chen, MICHAEL J MORRIS · 2001 to 2026
$63.0M
Tumor Evolution and Changes in MetabolismP50CA086438 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI RIVIERI, ISABELLE · 2000 to 2015
$29.9M
Molecular Imaging: Training for OncologyR25CA096945 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI HRICAK, HEDVIG · 2002 to 2013
$5.2M
Memorial Sloan Kettering Small Animal Imaging ResearchR24CA083084 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI KOUTCHER, JASON ARTHUR · 1999 to 2006
$4.4M
Foundations of Pretargeted RadioimmunotherapyR01CA101830 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 2005 to 2014
$2.7M
NanoSPECT/CT for Oncology ResearchS10RR028889 · NCRR · SLOAN-KETTERING INST CAN RESEARCH · PI ZANZONICO, PAT B · 2011 to 2011
$907k
NCI NIH HHS P30 CA008748NCI NIH HHS P30-CA08748NCI NIH HHS P50 CA086438NCI NIH HHS P50 CA092629NCI NIH HHS P50-CA86438NCI NIH HHS P50-CA92629NCI NIH HHS R01 CA101830NCI NIH HHS R01-CA-101830NCI NIH HHS R24 CA083084NCI NIH HHS R24-CA83084NCI NIH HHS R25 CA096945NCI NIH HHS R25-CA096945NCRR NIH HHS 1 S10 RR028889-01NCRR NIH HHS S10 RR028889
6 · The paper itself

Abstract

purposeGPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex.

methodsPRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens (177)Lu-or (86)Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model.

resultsUsing optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq (177)Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm(3)) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm(3) tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten (86)Y-DOTA-Bn.

conclusionWe have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts.

Indexed as

Antibody AffinityRadioimmunotherapyAnimalsAntibodies, BispecificColorectal NeoplasmsImmunoconjugatesImmunoglobulin GLutetiumMembrane GlycoproteinsMiceRadiopharmaceuticalsSingle-Chain AntibodiesXenograft Model Antitumor AssaysYttrium RadioisotopesAntibodies, BispecificGpa33 protein, mouseImmunoconjugatesImmunoglobulin GLutetiumMembrane GlycoproteinsRadiopharmaceuticalsSingle-Chain AntibodiesYttrium RadioisotopesBispecific antibodiesGPA33Multistep targetingPretargetingRadioimmunotherapy

Identifiers

PMID26596724
PMCPMC4814317
OpenAlexW2180753082

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Registered trials

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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.