(111)INDIUM LABELING OF HEPATOCYTES FOR ANALYSIS OF SHORT-TERM BIODISTRIBUTION OF TRANSPLANTED CELLS

Hepatocyte transplantation is useful for ex vivo gene therapy and live r repopulation. Methods for hepatic reconstitution have recently been developed but optimization of hepatocyte transplantation systems is ne cessary. To develop systems for noninvasive assessment of the biodistr ibution of transplanted cells, we labeled hepatocytes with (111)indium -oxine. Our initial studies showed that hepatocytes incorporated (111) -indium-oxine with an efficiency of approximately 20%. After labeling, cell viability was unchanged and (111)indium was present in hepatocyt es after overnight culture, as well as after intrasplenic transplantat ion. Transplanted cells were successfully localized by means of scinti graphic imaging. The scintigraphic patterns of cell distribution were different when hepatocytes were transplanted by means of either spleen or internal jugular vein, which deposit cells into separate vascular beds. Quantitative analysis of the biodistribution of (111)indium-labe led hepatocytes indicated that within 2 hr of intrasplenic transplanta tion, cells were predominantly localized in liver and spleen, and occa sionally in lungs. To determine whether the rate of intrasplenic cell injection influenced translocation of hepatocytes, we transplanted cel ls in normal rats. Despite intrasplenic cell injection at a variety of rates, organ-specific distribution of (111)indium-labeled hepatocytes remained unchanged. Labeling with (111)indium did not affect long-ter m survival of transplanted hepatocytes. These results indicate that (1 11)indium-labeling of hepatocytes should greatly assist noninvasive an alysis in the short-term of the biodistribution of transplanted hepato cytes.