| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Radiolabeled monoclonal antibodies (MoAb) can target tumors selectively. However, several problems limit their clinical application for radioimmunodetection (RID) and radioimmunotherapy (RIT). Liposomes, a potential drug carrier, can be made target-specific by immobilizing antibodies on their surface and can deliver a sufficient amount of radiolabel for therapy. We evaluated the potential of immunoliposomes for RID and RIT.
Murine monoclonal IgG MM (Ly) 2a1 that recognizes a MM46 tumor surface antigen was used. Intact IgG, its fragments F (ab') 2 or Fab' were coupled to liposomal surface and various radiolabels were encapsulated in liposomal inner aqueous phase. All of three immunoliposomes specifically recognized and bound to MM46 tumor cells in vitro and were specifically localized in the tumor in MM46 tumor-bearing mice. Tumor accumulation of Fab'-coupled liposomes encapsulating ^<111>In-NTA, which showed the best result, reached the maximum (28.5% administered dose/g) at 6 h after i
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ntravenous injection and was maintained at high level over 24 h. This value was much larger than that of ^<125>I-labeled Fab' alone and was higher than ^<125>I-intact MoAb at that. The blood clearance of Fab'-coupled liposomes was faster than that of intact MoAb alone, so that tumor-to-blood ratio at 24 h after injection reached 13.8, 3.5-fold higher than intact MoAb. Although the liposomes used in this study can reach the tumor site by themselves, the MoAb on the liposomal surface specifically binds to the target cells, resulting in larger tumor accumulation than the bare-liposomes. In spite of Fab' fragment, excellent tumor uptake was obtained by coupling to liposomes and renal uptake, an untoward effect of radiolabeled Fab', was not observed. In addition, by selecting an appropriate radionuclide, the target to non-target dosage was increased.
In conclusion, the MoAb-coupling liposomes proved to be tumor-targeting and improved tumor-to-nontumor ratios, which indicated the potency of immunoliposomes for RID and RIT.It should be an additional advantage to RIT that liposomes can be labeled with any nuclides, such as ^<89>Y, ^<189>Re or ^<188>Re, in large quantity. Less
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