Recent trends in antibody-based oncologic imaging

Abstract

Antibodies, with their unmatched ability for selective binding to any target, are considered as potentially the most specific probes for imaging. Their clinical utility, however, has been limited chiefly due to their slow clearance from the circulation, longer retention in non-targeted tissues and the extensive optimization required for each antibody-tracer. The development of newer contrast agents, combined with improved conjugation strategies and novel engineered forms of antibodies (diabodies, minibodies, single chain variable fragments, and nanobodies), have triggered a new wave of antibody-based imaging approaches. Apart from their conventional use with nuclear imaging probes, antibodies and their modified forms are increasingly being employed with non-radioisotopic contrast agents (MRI and ultrasound) as well as newer imaging modalities, such as quantum dots, near infra red (NIR) probes, nanoshells and surface enhanced Raman spectroscopy (SERS). The review article provides new developments in the usage of antibodies and their modified forms in conjunction with probes of various imaging modalities such as nuclear imaging, optical imaging, ultrasound, MRI, SERS and nanoshells in preclinical and clinical studies on the diagnosis, prognosis and therapeutic responses of cancer.

Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

“…[7][8][9][10] Cancer NIR molecular imaging relies greatly on the development of stable, highly specific and sensitive molecular probes. [11][12][13][14][15][16] Organic dyes such as indocyanine green have been used as nontargeted agents for optical imaging of cancer and have been used clinically for many years. 17,18 By combining these two molecules, we have developed a novel nitroimidazole indocyanine dye conjugate (2-nitroimidazole-ICG dye conjugate) for tumor-targeted hypoxia fluorescence tomography.…”

PET Imaging of Colorectal and Breast Cancer by Targeting EphB4 Receptor with64Cu-Labeled hAb47 and hAb131 Antibodies

“…However, both absolute tumor uptake and the pharmacokinetics of these probes need to be further improved. Antibodies are considered as potentially the most specific probes for imaging because they offer an unmatched ability to bind selectively to any target (30). Recently, anti-EphB4 antibodies have been obtained for EphB4 binding with 1 nM affinity.…”

Magical Bullets: A New Era of Molecular Imaging

“…PET is a highly sensitive functional imaging modality and enables quantitative imaging. The physical properties of a specific PET isotope radionuclide, including its half-life, positron yield, positron range, and overall decay scheme (including additional emissions) will determine suitability for an antibody imaging application (Salsano et al, 2013;Zhao et al, 2008;Kaur et al, 2012) The mAb (Monoclonal Antibodies) with it's best characteristics in binding affinity, blood clearance, and tumor penetration improves the imaging performance (Figure1). Alternative ligands have also been developed, among which antibody fragments and engineered variants such as antigen-binding F(ab')2 and F(ab'), singlechain variable fragments (scFv), diabodies, and minibodies (molecular weights ranging from 25-100 kDa) most commonly used.…”

“…Affibodies in particular are very stable and highly water-soluble α-helical proteins, with facilitated conjugation chemistry. In particular, the small size, resulting in rapid blood clearance, good tumor penetration, and high binding affinity to, selected targets, makes affibody molecules ideal candidates for imaging purposes (Kaur, 2012;Olafsen et al, 2010).…”