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Electropermeabilization in Experimental Tumour Treatment: Dosimetry and Tissue Effects

Engström, Per LU (1999)
Abstract
Short, electric high-voltage pulses can be used to transiently increase the permeability of cell membranes without significant loss of cell viability. During this period of time, extracellular and normally non-permeant, molecules are accessed the cytoplasm and the cell nucleus. This technique is called electroporation or electropermeabilization (EP). EP has been employed in vivo to internalise anticancer agents (bleomycin and cisplatin) into solid tumours. A large number of animal studies and several independent clinical trials have proven this technique to be efficient in many cases. It has recently been reported that EP also can be used to achieve high transfection efficiency of genes and proteins into tissues (e.g. muscle, liver and... (More)
Short, electric high-voltage pulses can be used to transiently increase the permeability of cell membranes without significant loss of cell viability. During this period of time, extracellular and normally non-permeant, molecules are accessed the cytoplasm and the cell nucleus. This technique is called electroporation or electropermeabilization (EP). EP has been employed in vivo to internalise anticancer agents (bleomycin and cisplatin) into solid tumours. A large number of animal studies and several independent clinical trials have proven this technique to be efficient in many cases. It has recently been reported that EP also can be used to achieve high transfection efficiency of genes and proteins into tissues (e.g. muscle, liver and tumours) in vivo. This thesis investigates techniques to determine the efficiency of in vivo electropermeabilization and to investigate and optimise parameters governing the treatment outcome. In Paper II, radiolabelled bleomycin (111In-BLMC) was internalised by EP into s.c. rat brain tumours and traced continuously with a gamma camera. In Paper III gamma camera measurements of radiolabelled DTPA was used to study the influence of various pulse parameters on the drug uptake in muscle tissue after EP. Paper IV describes a technique for instant measurements of the EP efficiency by impedance spectrometry. The conductivity change in skeletal muscle before and after EP was measured and correlated to concomitant 99mTc-DTPA measurements. The thesis also includes two studies of tumour treatment using EP. Paper V describes the antitumour effect of combined radiation and EP treatment, as well as observed detrimental effect on tumour vasculature after repeated EP treatment. In Paper VI, an adenocarcinoma implanted in rat liver was treated with bleomycin, internalised into the tumour by EP. A 92% cure rate with a pronounced anti-metastasising effect was observed for EP-bleomycin treated animals, which suggests a stimulation of the immune defence. Macrophages and CD8 positive lymphocytes were found in viable tumour of EP+bleomycin treated animals. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Heller, Richard, Department of Surgery, College of Medicine, University of South Florida, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
liver, electroporation, ischemia, Electropermeabilization, ECT, Tumor, 111-In-BLMC, 99m-Tc-DTPA, glioma, rat, electric pulses, Impedance spectrometry, treatment, Physics, Fysik
pages
150 pages
publisher
Department of Radiation Physics, Lund university
defense location
Lecture hall F3, University Hospital, Lund
defense date
1999-12-17 10:15
external identifiers
  • Other:ISRN: LUNFD6/(NFRA-1041)/1-62/1999
ISBN
91-628-3949-7
language
Other
LU publication?
yes
id
8e73f937-ca79-4db0-bc30-025d57a373b8 (old id 40086)
date added to LUP
2007-08-01 11:49:13
date last changed
2016-09-19 08:45:12
@phdthesis{8e73f937-ca79-4db0-bc30-025d57a373b8,
  abstract     = {Short, electric high-voltage pulses can be used to transiently increase the permeability of cell membranes without significant loss of cell viability. During this period of time, extracellular and normally non-permeant, molecules are accessed the cytoplasm and the cell nucleus. This technique is called electroporation or electropermeabilization (EP). EP has been employed in vivo to internalise anticancer agents (bleomycin and cisplatin) into solid tumours. A large number of animal studies and several independent clinical trials have proven this technique to be efficient in many cases. It has recently been reported that EP also can be used to achieve high transfection efficiency of genes and proteins into tissues (e.g. muscle, liver and tumours) in vivo. This thesis investigates techniques to determine the efficiency of in vivo electropermeabilization and to investigate and optimise parameters governing the treatment outcome. In Paper II, radiolabelled bleomycin (111In-BLMC) was internalised by EP into s.c. rat brain tumours and traced continuously with a gamma camera. In Paper III gamma camera measurements of radiolabelled DTPA was used to study the influence of various pulse parameters on the drug uptake in muscle tissue after EP. Paper IV describes a technique for instant measurements of the EP efficiency by impedance spectrometry. The conductivity change in skeletal muscle before and after EP was measured and correlated to concomitant 99mTc-DTPA measurements. The thesis also includes two studies of tumour treatment using EP. Paper V describes the antitumour effect of combined radiation and EP treatment, as well as observed detrimental effect on tumour vasculature after repeated EP treatment. In Paper VI, an adenocarcinoma implanted in rat liver was treated with bleomycin, internalised into the tumour by EP. A 92% cure rate with a pronounced anti-metastasising effect was observed for EP-bleomycin treated animals, which suggests a stimulation of the immune defence. Macrophages and CD8 positive lymphocytes were found in viable tumour of EP+bleomycin treated animals.},
  author       = {Engström, Per},
  isbn         = {91-628-3949-7},
  keyword      = {liver,electroporation,ischemia,Electropermeabilization,ECT,Tumor,111-In-BLMC,99m-Tc-DTPA,glioma,rat,electric pulses,Impedance spectrometry,treatment,Physics,Fysik},
  language     = {mis},
  pages        = {150},
  publisher    = {Department of Radiation Physics, Lund university},
  school       = {Lund University},
  title        = {Electropermeabilization in Experimental Tumour Treatment: Dosimetry and Tissue Effects},
  year         = {1999},
}