Biodistribution and Imaging of Polyethyleneimine-A Gene Delivery Agent

Abstract

Polyethyleneimine (PEI) has been described as a potentially effective agent for gene delivery. To track the delivery of this gene vector, the biodistribution and imaging of PEI labeled with 111 Indium ( 111 In) was studied in Fischer 344 rats. PEI was conjugated with diethylenetriamine pentaacetic acid dianhydride (DTPA), dialyzed, and chelated with 111 In. Breast adenocarcinoma 13762 tumor cells were inoculated into the thighs of the rats. The rst group of rats (n = 3) were injected intravenously with 300 ¹g of the Indiumlabeled DTPA-polyethlyeimine ( 111 In-DTPA-PEI) (50 ¹Ci per rat) or 111 In-DTPA. These animals were imaged with a gamma camera with a medium energy parallel hole collimator at 5 min, 2 hr, and 24 hr postinjection. The percentage of uptake in tumor (region of interest) was quantitated by a computer image analyzer and expressed as a percentage of injected dose (%ID) per pixel. To further characterize the tissue distribution of 111 In-DTPA-PEI (300 l g, 10 ¹Ci per rat) and 111 In-DTPA (10 ¹Ci per rat), a second group of animals (n = 18) bearing breast tumors were studied with tissue uptake quanti ed at 2 hr, 24 hr, and 48 hr using a gamma counter. In addition, autoradiography was used to further characterize the distribution of the labeled polymer in two rats at 2 and 24 hr. From these studies, PEI was found to be rapidly cleared, primarily through the kidneys of the rats. In addition, the distribution of 111 In-DTPA-PEI was found to be signi cantly different from 111 In-DTPA with a higher tumor-to-blood ratio. These studies show that radio-labeled PEI may have potential as a gamma scintigraphy imaging agent and in tracking the delivery of genetic material.

Characterization of poly(ethylene imine) layers on mica by the streaming potential and particle deposition methods

“…They are widely used in the paper [1,2] and in the food industry [3,4], in the life sciences [5], and for gene transfer in molecular medicine [6][7][8]. To understand how the properties of practical systems are influenced by polyion presence it is essential to gain knowledge about mechanisms of polyelectrolyte adsorption.…”

Polyethylenimine Complexes with Retinoic Acid: Structure, Release Profiles, and Nanoparticles

“…For example, PEI has been reported to promote transgene delivery to the nucleus in mammalian cells, 2 and it has been proposed as a potential gamma scintigraphy imaging agent. 3 In comparison to viral vectors, the vectors formed by PEI-DNA complexes retain high attractiveness in gene therapy due to their theoretically excellent safety profile. In addition to the complexation of DNA, PEI has a strong tendency to form complexes with anionic surfactants.…”

Probing In Vivo Trafficking of Polymer/DNA Micellar Nanoparticles Using SPECT/CT Imaging

“…10 DNA nanoparticles are formed by electrostatic interaction between cationic polymer/lipid and plasmid DNA, and might be prone to dissociation in vivo upon contact with high ionic strength buffers and charged macromolecules, hence resulting in misinterpretation of the biodistribution of DNA. Therefore we had preferred radiolabeling of the DNA over radiolabeling of the polymer.…”