Biodistribution and Imaging of Polyethyleneimine-A Gene Delivery Agent

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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 111Indium (111In) was studied in Fischer 344 rats. PEI was conjugated with diethylenetriamine pentaacetic acid dianhydride (DTPA), dialyzed, and chelated with 111In. Breast adenocarcinoma 13762 tumor cells were inoculated into the thighs of the rats. The first group of rats (n = 3) were injected intravenously with 300 mu g of the Indiumlabeled DTPA-polyethlyeimine (111In-DTPA-PEI) (50 mu Ci per rat) or 111In-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 111In-DTPA-PEI (300 mu g, 10 mu Ci per rat) and 111In-DTPA (10 mu Ci per rat), a second group of animals (n = 18) bearing breast tumors were studied with tissue uptake quantified 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 111In-DTPA-PEI was found to be significantly different from 111In-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.