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Effect of interleukin-2 on the biodistribution of technetium-99m-labelled anti-CEA monoclonal antibody in mice bearing human tumour xenografts. 1994

K Nakamura, and A Kubo
Department of Radiology, School of Medicine, Keio University, Tokyo, Japan.

We have evaluated whether interleukin-2 (IL-2) at low doses can enhance delivery of radionuclides to tumour sites by improving the access of the radio-labelled antibody. The effects of 1000 or 2000 units of IL-2 on the biodistribution of technetium-99m-labelled anticarcinoembryonic antigen (CEA) monoclonal antibody, ZCE025, in athymic mice bearing human CEA-positive tumour (MKN45) xenografts were investigated. Treatment with IL-2 resulted in a significantly higher tumour uptake (1.2-1.5-fold) compared with the control group. Some normal organs, such as heart, lung, liver, spleen and kidneys, showed increased 99mTc uptake following the IL-2 treatment. Pretreatment with IL-2 also induced an enhancement of the permeability index for mouse IgG in tumours and in normal organs, whereas the blood flow in both normal organs and tumours remained at control levels. The effects of IL-2 were found to be dose-dependent. The IL-2 treatment increased the plasma CEA levels but not the CEA content in tumour tissues, suggesting that IL-2 enhanced the leakage of CEA from tumour to blood. The enhancement ratios of the tumour 99mTc-ZCE025 uptake following treatment with IL-2 were 1.4 and 1.8 in mice bearing small and large tumours, respectively. Our experimental results indicated that the low dose of IL-2 enhanced the vascular permeability sufficiently to increase the amount of antibody delivered to the tumour target. Administration of IL-2 would render radioimmunotherapy more effective, especially in patients with large tumour burdens.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002199 Capillary Permeability The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement. Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013670 Sodium Pertechnetate Tc 99m A gamma-emitting radionuclide imaging agent used for the diagnosis of diseases in many tissues, particularly in the gastrointestinal system, cardiovascular and cerebral circulation, brain, thyroid, and joints. Pertechnetate Sodium,Tc 99m-Pertechnetate,Technetium Tc 99m Pertechnetate,99Tc-Pertechnetate,99TcmO4,99mTcO4,Pertechnetate,Technetium Pertechnetate,Technetium Tc 99m O(4),Technetium-99mTc-pertechnetate,99Tc Pertechnetate,99m-Pertechnetate, Tc,Pertechnetate, Technetium,Sodium, Pertechnetate,Tc 99m Pertechnetate,Technetium 99mTc pertechnetate

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