99m Tc labelled model drug carriers - labeling, stability and organ distribution in rats Gerd Wunderlich a, *, Thomas Gru ¨ning a , Bernd-R. Paulke b , Antje Lieske b , Jo ¨rg Kotzerke a a Department of Nuclear Medicine, Carl Gustav Carus Medical School, University of Technology, Dresden, Germany b Fraunhofer Institute of Applied Polymer Research, Teltow-Seehof/Golm, Germany Received 21 March 2003; received in revised form 10 June 2003; accepted 26 June 2003 Abstract The surface characteristics of intravenously administered particulate drug carriers decisively influence the protein adsorption that is regarded as a key factor for the in vivo fate of the carriers. We labeled surface-modified polymer particles with the -emitting radioisotope 99m Tc in order to test their properties in blood and follow their in vivo fate. The biodistribution was different in various types of polymer particles. As expected, labeled particles were found in the mononuclear phagocyte system in a large scale but markedly different biodistribution for some particles were also shown. © 2004 Elsevier Inc. All rights reserved. Keywords: Polymer particles; Drug targeting; Radiolabelling; Biodistribution 1. Introduction The nonspecific interaction between proteins and poly- mer surfaces (membranes, colloidal particles, etc.) deter- mines the in vivo fate of drug carriers [1,13,18]. Intrave- nously administered particulate drug carriers are one approach to site-specific delivery of drugs as well as in pharmaceutics in general as in radiopharmacy paticularly [17,19]. The immunological recognition of these particles by cells of the mononuclear phagocyte system (MPS) is a major obstacle to this application. Since the in vivo bioki- netics of intravenously administered nanoparticles is strongly influenced by their interactions with blood compo- nents, enrichment of certain proteins might be able to direct the particles to specific target cells or tissues. Exemplarily, this could be shown for particles with ApoE enrichment on the surface to target drugs to the brain [7,12]. The motivation of this work was to examine the hypoth- esis, a passive, organ-specific drug targeting could be achieved exclusively by a controlled variation of physico- chemical carrier surface properties mediated by the plasma protein adsorption patterns that result from blood contact after intravenous injection. After detailed studies of the influence of physico-chem- ical properties such as surface hydrophobicity [8] and sur- face charge density [6] of model polymer colloids on the protein adsorption from human plasma, our interest focused on the in vivo distribution of such modified particles. In previous studies, considerable differences in protein adsorp- tion onto the latex particles were detected with regard to the total amount of surface-bound protein as well as specific proteins adsorbed by various particle types, e. g. fibrinogen, albumin, and plasma glycoprotein [11]. Correlations could be shown between protein adsorption patterns and the phys- icochemical characteristics of polymer surfaces [4,10]. In this study, we labeled surface-modified polymer par- ticles with the -emitting radioisotope 99m Tc in order to follow their in vivo fate. A ‘gentle’ radioactive labeling method, i.e. with low alterations of surface properties, was used for this purpose. The stability of labeled particles was tested in human serum and the particles were injected intrave- nously in Wistar rats to investigate their in vivo distribution. 2. Materials and methods 2.1. Particle synthesis and characterization Latex preparation was performed by different techniques of emulsion polymerization as described previously [16]. * Corresponding author. Tel.: +49-351-4582128; Fax: +49-351- 4585347. E-mail address: gerd.wunderlich@mailbox.tu-dresden.de (G. Wunder- lich). Nuclear Medicine and Biology 31 (2004) 87–92 www.elsevier.com/locate/nucmedbio 0969-8051/04/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0969-8051(03)00120-3