Tumor targeting potential of liposomes encapsulating Ga-67 and antibody to Dalton's lymphoma associated antigen (anti-DLAA).
Dalton's lymphoma (solid tumor) was induced in Swiss mice by an 'Air-pouch' technique using ascites cells. A liposomal technique for radioimmunodetection and localization using Ga-67 and antibody has been developed. Dalton's lymphoma associated antigen (DLAA) was isolated and purified by ammonium sulfate fractionation and chromatography. The antibody to this antigen, anti-DLAA, was prepared by immunization of rabbits and purified by CNBr activated chromatography. The specificity of this antibody to the solid tumor antigen was ascertained by agar gel diffusion. Scintiscan studies were carried out using controls and Dalton's lymphoma bearing mice at various time intervals after i.p. administration of 10-20 mu ci of Ga-67, Ga-67 Ga-67 as liposomes and Ga-67 incorporated with antibody to DLAA as liposomes. Extensive studies carried out using liposomes of different sizes and charges revealed that anti-DLAA significantly improved the tumor uptake of Ga-67, thereby facilitating better visualization of the tumor. Negative and neutral liposomes delivered maximum radioactivity at the target tissue, whereas positive liposomes did not cause significant tumor accumulation of 67Ga. Biodistribution studies showed maximum tumor-associated activity that is 15.43% of the injected dose per gram tumor tissue was achieved with Ga-67 anti-DLAA liposomes compared to 6.6% with Ga-67 administered as such. Injection of Ga-67 liposome resulted in minimum tumor-associated activity that is 5.33%, with maximum uptake by liver and spleen. This might be caused by accumulation of liposomes in these organs. Incorporation of anti-DLAA might significantly improve uptake of Ga-67 by target tissue, due to the specificity of the antigen antibody reaction.
Udayachander
M
M
Biochemistry Department, Cancer Institute, Adyar, Madras, India.
Meenakshi
A
A
Muthiah
R
R
Sivanandham
M
M
D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000276:immunology; D051379:Mice; D011817:Rabbits; D011877:Radionuclide Imaging; D013154:Spleen / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D005710:Gallium Radioisotopes; D008081:Liposomes