Bone marrow toxicity in mice treated with indium-114m-labelled blood cells.

Abstract

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.