Biodistribution of immunoliposome labeled with Tc-99m in tumor xenografted mice.
OBJECTIVE
Immunoliposome (PEG, GAH, liposome; PGL), consisting of F(ab')(2) fragment of monoclonal antibody, GAH and polyethyleneglycol-coated (PEGylated) liposome was provided. Immunoliposome, PGL was labeled with technetium-99m (Tc-99m) by two methods: labeling F(ab')(2) fragment with Tc-99m; Tc-99m-PGL, and entrapping Tc-99m into liposome; PGL[Tc-99m]. The objective of this study was to compare the biodistribution of Tc-99m-PGL and PGL[Tc-99m] in human gastric cancer xenografted mice.


METHODS
Tc-99m-PGL, PGL[Tc-99m], and Tc-99m-entrapped liposome; Lipo[Tc-99m] were prepared. They were injected into human gastric cancer, MKN45, xenografted mice via the tail vein, and their biodistribution was studied.


RESULTS
No marked accumulation of either PGL[Tc-99m] or Lipo[Tc-99m] was observed in the stomach. The uptake of Tc-99m-PGL by the liver, spleen, and lung was higher than that by the tumor. On the other hand, the uptake of PGL[Tc-99m] by the lung and spleen was markedly lower as compared with that of Tc-99m-PGL; the accumulation of PGL[Tc-99m] was lower in the lung and higher in the spleen as compared with that of the tumor. Although the liver uptake of PGL[Tc-99m] was markedly decreased as compared with that of Tc-99m-PGL, it was higher than the uptake of the tumor. The Tc-99m-PGL was strongly taken up by the tumor, with a high level of incorporation also seen in the stomach. These findings suggest the need for further study of the labeling stability.


CONCLUSIONS
PGL[Tc-99m] appears to show promise for high tumor uptake and retention. This is an important implication for the potential application of immunoliposomes entrapped with Re-186, instead of Tc-99m, in internal radiotherapy.
Kitamura
Naoto
N
Department of Radiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yib03642@nifty.ne.jp
Shigematsu
Naoyuki
N
Nakahara
Tadaki
T
Kanoh
Momoe
M
Hashimoto
Jun
J
Kunieda
Etsuo
E
Kubo
Atsushi
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011092:Polyethylene Glycols / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013154:Spleen / Q000378:metabolism; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D013667:Technetium