TY - JOUR
T1 - Biodistribution and imaging of polyethyleneimine - A gene delivery agent
AU - Nichol, Carolyn A.
AU - Yang, David
AU - Humphrey, Wendy
AU - Ilgan, Seyfettin
AU - Tansey, Wayne
AU - Higuchi, Tetsuya
AU - Zareneyrizi, Fereshteh
AU - Wallace, Sidney
AU - Podoloff, Donald A.
PY - 1999
Y1 - 1999
N2 - 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 μg of the Indium-labeled DTPA-polyethlyeimine (111In-DTPA-PEI) (50 μCi 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 μg, 10 μCi per rat) and 111In- DTPA (10 μCi 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.
AB - 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 μg of the Indium-labeled DTPA-polyethlyeimine (111In-DTPA-PEI) (50 μCi 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 μg, 10 μCi per rat) and 111In- DTPA (10 μCi 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.
KW - Biodistribution
KW - Imaging
KW - Indium
KW - Polyethyleneimine
KW - Scintigraphy
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U2 - 10.1080/107175499266940
DO - 10.1080/107175499266940
M3 - Article
AN - SCOPUS:0032875759
SN - 1071-7544
VL - 6
SP - 187
EP - 194
JO - Drug Delivery: Journal of Delivery and Targeting of Therapeutic Agents
JF - Drug Delivery: Journal of Delivery and Targeting of Therapeutic Agents
IS - 3
ER -