An engineered cysteine-modified diabody for imaging activated leukocyte cell adhesion molecule (ALCAM)-positive tumors.
Purpose: The purpose of this study was to generate and evaluate a positron emission tomography (PET) radiotracer targeting activated leukocyte cell adhesion molecule (ALCAM).Procedures: A human anti-ALCAM single chain variable fragment was reformatted to produce a covalent dimer, termed a cys-diabod...
| Publicado en: | Molecular Imaging & Biology Vol. 14; no. 3; pp. 336 - 348 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Jun2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104443613&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104443613 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Jun2012 vid: 14 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104443613 NLM21630083 2011752275 10.1007/s11307-011-0500-8 NLM21630083 PMC3227780 104443613 ppf: 336 ppct: 12 formats: fmt: @attributes: type: P tig: atl: An engineered cysteine-modified diabody for imaging activated leukocyte cell adhesion molecule (ALCAM)-positive tumors. aug: au: McCabe KE Liu B Marks JD Tomlinson JS Wu H Wu AM McCabe, Katelyn E Liu, Bin Marks, James D Tomlinson, James S Wu, Hong Wu, Anna M affil: Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA sug: subj: Antigens, Surface Metabolism Cysteine Metabolism Genetic Engineering Methods Immunoglobulins, Fab Metabolism Tomography, Emission-Computed Methods Tumor Markers, Biological Metabolism Animal Studies Antigens, Surface Analysis Cells Cysteine Female Human Immunoglobulins, Fab Mice Neoplasms Neoplasms Metabolism Organometallic Compounds Pancreatic Neoplasms Metabolism Radioisotopes Rats Tumor Markers, Biological Analysis Female ab: Purpose: The purpose of this study was to generate and evaluate a positron emission tomography (PET) radiotracer targeting activated leukocyte cell adhesion molecule (ALCAM).Procedures: A human anti-ALCAM single chain variable fragment was reformatted to produce a covalent dimer, termed a cys-diabody (CysDb). Purified CysDb was characterized by gel electrophoresis and size exclusion chromatography, and immunoreactivity was assessed by flow cytometry and immunofluorescence. Targeting and imaging of ALCAM-positive tumors using (64)Cu-DOTA-CysDb were evaluated in mice bearing human pancreatic adenocarcinoma xenografts (HPAF-II or BxPC-3).Results: CysDb binds specifically to ALCAM-positive cells in vitro with an apparent affinity in the range of 1-3 nM. MicroPET images at 4 h showed specific targeting of positive tumors in vivo, a finding confirmed by biodistribution analysis, with positive/negative tumor ratios of 1.9 ± 0.6 and 2.4 ± 0.6, and positive tumor/blood ratios of 2.5 ± 0.9 and 2.9 ± 0.6 (HPAF-II and BxPC-3, respectively).Conclusions: Successful imaging with (64)Cu-DOTA-CysDb in animal models suggests further investigation of ALCAM as an imaging biomarker is warranted. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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