Applying PET to broaden the diagnostic utility of the clinically validated CA19.9 serum biomarker for oncology Journal Article


Authors: Viola-Villegas, N. T.; Rice, S. L.; Carlin, S.; Wu, X.; Evans, M. J.; Sevak, K. K.; Drobnjak, M.; Ragupathi, G.; Sawada, R.; Scholz, W. W.; Livingston, P. O.; Lewis, J. S.
Article Title: Applying PET to broaden the diagnostic utility of the clinically validated CA19.9 serum biomarker for oncology
Abstract: Despite their considerable advantages, many circulating biomarkers have well-documented limitations. One prominent shortcoming in oncology is a high frequency of false-positive indications for malignant disease in upfront diagnosis. Because one common cause of false positivism is biomarker production from benign disorders in unrelated host tissues, we hypothesized that probing the sites of biomarker secretion with an imaging tool could be a broadly useful strategy to deconvolute the meaning of foreboding but inconclusive circulating biomarker levels. In preparation to address this hypothesis clinically, we developed (89)Zr-5B1, a fully human, antibody-based radiotracer targeting tumor-associated CA19.9 in the preclinical setting. (89)Zr-5B1 localized to multiple tumor models representing diseases with undetectable and supraphysiologic serum CA19.9 levels. Among these, (89)Zr-5B1 detected orthotopic models of pancreatic ductal adenocarcinoma, an elusive cancer for which the serum assay is measured in humans but with limited specificity in part because of the frequency of CA19.9 secretion from benign hepatic pathologies. In this report, a general strategy to supplement some of the shortcomings of otherwise highly useful circulating biomarkers with immunoPET is described. To expedite the clinical validation of this model, a human monoclonal antibody to CA19.9 (a highly visible but partially flawed serum biomarker for several cancers) was radiolabeled and evaluated, and the compelling preclinical evidence suggests that the radiotracer may enhance the fidelity of diagnosis and staging of pancreatic ductal adenocarcinoma, a notoriously occult cancer.
Keywords: positron emission tomography; methodology; neoplasm; neoplasms; mouse; animal; animals; mice; tumor markers, biological; pathology; cell line, tumor; tumor antigen; tumor marker; cell transformation, neoplastic; monoclonal antibody; blood; antibodies, monoclonal; diagnostic agent; cell transformation; tumor cell line; positron-emission tomography; scintiscanning; pancreas adenocarcinoma; pet imaging; pancreatic adenocarcinoma; radioisotope; radioisotopes; zirconium; antigens, tumor-associated, carbohydrate; humans; human; female; article; ca19.9; carbohydrate antigen 199, human
Journal Title: Journal of Nuclear Medicine
Volume: 54
Issue: 11
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2013-11-01
Start Page: 1876
End Page: 1882
Language: English
PUBMED: 24029655
PROVIDER: scopus
DOI: 10.2967/jnumed.113.119867
PMCID: PMC4274751
DOI/URL:
Notes: Export Date: 3 February 2014 -- Source: Scopus
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MSK Authors
  1. Govindaswami Ragupathi
    144 Ragupathi
  2. Samuel Rice
    14 Rice
  3. Xiaohong Wu
    6 Wu
  4. Michael John Evans
    22 Evans
  5. Jason S Lewis
    413 Lewis
  6. Sean Denis Carlin
    83 Carlin
  7. Kuntalkumar Sevak
    11 Sevak