Glycolaldehyde and maleyl conjugated human serum albumin as potential macrophage‐targeting carriers for molecular imaging purposes

We present a novel synthesis of glycolaldehyde‐conjugated human serum albumin (GA‐HSA) and maleylated human serum albumin (Mal‐HSA). Seventeen modifications of fluorescently tagged GA‐HSA and Mal‐HSA molecules with different degrees of conjugation were prepared. The comparative uptake studies, using 12 of these modifications, were done in vitro on mouse monocytes/macrophages (RAW264.7), and evaluated qualitatively by confocal microscopy and quantitatively by flow cytometry. The GA modifications are taken up by the macrophages approximately 40% better than the maleyl modifications at low concentrations (≤3 μm), while at higher concentrations it appears that the maleyl modifications are taken up around 25–44% better than the GA‐modified HSA. However, high uptake at low concentrations will be beneficial for in vivo localizing inflammation in areas with low penetration of the probe as in an atherosclerotic plaque. Further, another advantage of GA‐HSA is that GA competes less than the maleyl group for the free reactive amine sites that are to be used for conjugation of metal chelating ligands (e.g. tetraazacyclododecanetetraacetic acid and triazacyclononanetriacetic acid). Metal ions such as Gd3+ and Mn2+ can be chelated for positive Magnetic Resonance (MR) contrast and positron emitting ions such as 64Cu2+ and 68Ga3+ for Positron Emission Tomography (PET) imaging. These are important properties, especially, when considering the MR contrast possibilities owing t...

Source: Contrast Media and Molecular Imaging - April 21, 2014 Category: Radiology Authors: Björn Gustafsson, Ulf Hedin, Kenneth Caidahl Tags: Full Paper Source Type: research