Autologous lymphocytes as vectors to target therapeutic radiation, using indium‐114m, in patients with lymphoid cell malignancy

Abstract

Summary. Autologous lymphocytes provide a potential vector for the delivery of a cytotoxic agent in patients with lymphoid cell malignancy. This report describes a phase I–II study using autologous lymphocytes to target the radionuclide indium‐114m (114mIn) in patients with refractory chronic lymphocytic leukaemia or small lymphocytic non‐Hodgkin's lymphoma. Nineteen patients, the majority of whom had been heavily pretreated with conventional chemotherapy and radiotherapy, received between 69 and 211 MBq 114mIn‐labelled autologous lymphocytes. Approximately 80% of the administered activity was localized in the liver and spleen, with around 5% accumulating in the bone marrow. Ten patients (53%) responded (one complete response and nine partial responses). The median duration of response was 7 months. The median survival for the responders was 14 months and for the non‐responders was 3 months. The first notable response in every patient was a fall in peripheral lymphocyte count. The indium treatment was not associated with any subjective toxicity, although all patients suffered from myelosuppression, with thrombocytopenia being the dose‐limiting factor. This study has demonstrated a significant anti‐tumour effect in a group of patients with late‐stage highly resistant disease.

Radioactive Main Group and Rare Earth Metals for Imaging and Therapy

“…408,409 Neutron irradiation of enriched 113 In has also been reported. 410 In lieu of a detailed summary below, here we simply report that 114m In is capable of damaging cell DNA and the β − particle decay appears suitable for treatment of large tumors (>1 cm 3 ). 411,412 Indium-114m has undergone preclinical studies for palliative treatment of advanced lymphoid malignancy and for targeting of HER2-expressing malignant tumors, as well as clinical studies to treat lymphoid cell malignancy.…”

“…The use of nat Cd targets has been investigated, but coproduction of 111,113m In is unavoidable and yields are drastically decreased. , Neutron irradiation of enriched 113 In has also been reported . In lieu of a detailed summary below, here we simply report that 114m In is capable of damaging cell DNA and the β – particle decay appears suitable for treatment of large tumors (>1 cm 3 ). , Indium-114m has undergone preclinical studies for palliative treatment of advanced lymphoid malignancy and for targeting of HER2-expressing malignant tumors, as well as clinical studies to treat lymphoid cell malignancy. ,− …”

29 Inorganic pharmaceuticals

“…241 All of the above applications of non-chelated gallium and indium may be mediated through binding of the metal to plasma transferrin, a topic which has been reviewed recently. 242 Use of radiolabelled autologous lymphocytes 243 or heat damaged red blood cells 244 as a delivery vehicle for the therapeutic radionuclide In-114m to the spleen and bone marrow in has shown promising results in lymphocytic leukaemia patients with highly resistant disease.…”