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Mol Imaging Biol. 2012 Jun;14(3):336-47. doi: 10.1007/s11307-011-0500-8.

An engineered cysteine-modified diabody for imaging activated leukocyte cell adhesion molecule (ALCAM)-positive tumors.

Author information

  • 1Crump 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. kmccabe@ucla.edu

Abstract

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.

PMID:
21630083
[PubMed - indexed for MEDLINE]
PMCID:
PMC3227780
Free PMC Article

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