Lymphocyte targeted ricin as a potential therapy for lymphoid malignancy. I. Targeting efficiency.
Lymphocytes were studied as vehicles to target the plant toxin ricin, to lymphoid tissue in rats. Ricin-loaded thoracic duct lymphocyte (TDL) migrated normally into lymph nodes (LN) at 0.5 h, but this process was arrested by 3 h after injection. Ricin was successfully targeted to lymphoid tissue as evidenced by a 4-fold increase in ricin-associated radioactivity in LN, a 10-fold increase in the Peyers patches, a doubling in the spleen and a 35% reduction of radioactivity in the liver compared with free ricin. Nevertheless this represented a considerable shortfall in the expected targeting efficiency. The main problem was found to be high in vivo elution of ricin from TDL (70% within 0.5 h of i.v injection). This and other aspects relevant to maximising targeting efficiency are discussed.
Ramsden
C S
CS
Department of Cell and Structural Biology Medical School, University of Manchester, UK.
Drayson
M T
MT
Bell
E B
EB
D000818:Animals; D002465:Cell Movement; D002860:Chromium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000922:Immunotoxins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008221:Lymphoid Tissue / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
D002860:Chromium Radioisotopes; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D012276:Ricin