Biodistribution and imaging of polyethyleneimine - A gene delivery agent

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 (In-111) was studied in Fischer 344 rats. PEI was conjugated with diethylenetriamine pentaacetic acid dianhydride (DTPA), dialyzed, and chelated with In-111, 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 Indium-labeled DTPA-polyethlyeimine (In-111-DTPA-PEI) (50 mu Ci per rat) or In-111-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 In-111-DTPA-PEI (300 mu g, 10 mu Ci per rat) and In-111-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 In-111-DTPA-PEI was found to be significantly different from In-111-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.