Applying PET to Broaden the Diagnostic Utility of the Clinically Validated CA19.9 Serum Biomarker for Oncology

Autor: Nerissa Viola-Villegas, Marija Drobjnak, Ritsuko Sawada, Govind Ragupathi, Kuntal K. Sevak, Michael J. Evans, Philip O. Livingston, Jason S. Lewis, Samuel L. Rice, Sean Carlin, Xiaohong Wu, Wolfgang W. Scholz
Rok vydání: 2013
Předmět:
Oncology
PET imaging
Cell Transformation
CA19.9
Mice
Serum biomarkers
Neoplasms
Monoclonal
Cancer
screening and diagnosis
Tumor
medicine.diagnostic_test
biology
Antibodies
Monoclonal
Detection
Nuclear Medicine & Medical Imaging
Cell Transformation
Neoplastic
Positron emission tomography
Biomedical Imaging
Biomarker (medicine)
Female
CA19-9
Antibody
Carbohydrate
medicine.medical_specialty
medicine.drug_class
Clinical Sciences
Bioengineering
Monoclonal antibody
Antibodies
Article
Malignant disease
Cell Line
Pancreatic Cancer
Rare Diseases
Clinical Research
Cell Line
Tumor
Internal medicine
pancreatic adenocarcinoma
Biomarkers
Tumor
medicine
Animals
Humans
Antigens
Tumor-Associated
Carbohydrate
Radiology
Nuclear Medicine and imaging
Antigens
Radioisotopes
Neoplastic
business.industry
Tumor-Associated
medicine.disease
4.1 Discovery and preclinical testing of markers and technologies
Positron-Emission Tomography
biology.protein
Zirconium
Digestive Diseases
business
Biomarkers
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, vol 54, iss 11
ISSN: 2159-662X
0161-5505
DOI: 10.2967/jnumed.113.119867
Popis: UnlabelledDespite 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.MethodsIn 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.Results(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.ConclusionIn 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.
Databáze: OpenAIRE
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