Selective lymphoid irradiation. I. An approach to transplantation.
The kinetics, distribution, and radiobiologic effects of palladium (Pd)-109-hematoporphyrin were determined in the rat. In addition, we studied the effect on rat heart allograft survival of Pd-109-hematoporphyrin, with and without antilymphocyte serum (ALS). A single sublethal dose of Pd-109-hematoporphyrin (up to 36 muCi/kg) resulted in the following: predominant concentration in lymphoid tissue and proximal bone marrow, complete central and proximal bone marrow ablation with preservation of distal bone marrow, massive depletion of lymphocytes from lymph nodes and spleen, an 80% reduction in peripheral blood lymphocytes which was completed by the addition of ALS, full recovery of lymphoid tissue and blood cellularity within 60 days of administration of radionuclide, and a 100% animal survival rate. This method of selective lymphoid irradiation (SLI) prolongs indefinitely Fisher cardiac allografts in Lewis recipients and significantly prolongs cardiac allograft survival across major histocompatibility barries (ACI to Lewis or to Fisher). Specific tolerance to donor strains was demonstrated by the acceptance of Fisher skin by Lewis recipients carrying 150-day-old Fisher hearts. Third party (ACI) skin allografts were rapidly rejected by the same animals. Further studies of SLI in larger animals are required to determine the optimal safe dose of SLI in man.
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006084:Graft Rejection / Q000528:radiation effects*; D006085:Graft Survival / Q000528:radiation effects; D016027:Heart Transplantation; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000378:metabolism; D007108:Immune Tolerance; D008212:Lymphocyte Depletion / Q000379:methods*; D008221:Lymphoid Tissue / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D010165:Palladium / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D011868:Radioisotopes / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D016038:Skin Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D006415:Hematoporphyrins; D011868:Radioisotopes; D010165:Palladium