Bone marrow toxicity in mice treated with indium-114m-labelled blood cells.
Clinical trials with autologous indium-114m-labelled lymphocytes have revealed significant anti-tumour effects in chronic lymphocytic leukaemia patients with highly resistant disease. Substitution of the lymphocyte vector with heat-damaged red blood cells (HDRBC) may make this treatment more universally applicable and reduce the dose-limiting myelosuppression encountered with labelled lymphocytes. Therefore, the bone marrow localization and toxicities of indium-labelled lymphocytes or HDRBC have been investigated in BDFI mice. At 24 hours approximately 4% and 1.2% of 114In(m) administered as labelled lymphocytes or HDRBC respectively was localized within the bone marrow and remained constant for 57 days thereafter. Toxicity towards bone marrow stem cells, measured as CFU-S, was equivalent for both cellular vectors. However, at clinically relevant activities, 114In(m) HDRBC were less toxic than labelled lymphocytes towards committed progenitors, assayed as in vitro-CFC and CFU-Meg. These data suggest that substitution of HDRBC for lymphocytes as the 114In(m) vector may be beneficial in reducing the myelosuppression associated with this technique.
Hoyes
K P
KP
CRC Dept. of Experimental Haematology, Paterson Institute for Cancer Research, University of Manchester, UK.
Wadeson
P J
PJ
Murby
B
B
Sharma
H L
HL
Cowan
R A
RA
Lord
B I
BI
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000378:metabolism*; D005269:Femur / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D006979:Hyperthermia, Induced; D007205:Indium Radioisotopes / Q000009:adverse effects*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000532:radiotherapy; D017710:Lymphocyte Transfusion; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000378:metabolism* / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology; D014018:Tissue Distribution
D007205:Indium Radioisotopes