Preparation and evaluation of the rhenium-188-labelled anti-NCA antigen monoclonal antibody BW 250/183 for radioimmunotherapy of leukaemia

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Ulrike Seitz - , Ulm University (Author)
  • Bernd Neumaier - , Ulm University (Author)
  • Gerhard Glatting - , Ulm University (Author)
  • Jörg Kotzerke - , Ulm University (Author)
  • Donald Bunjes - , Ulm University (Author)
  • Sven N. Reske - , Ulm University (Author)

Abstract

Anti-NCA antigen antibody BW 250/183 (Anti-Granulocyte) localizes more than 50% of injected antibody dose to the bone marrow. Therefore, this antibody is promising for adjuvant conditioning radioimmunotherapy of bone marrow before bone marrow transplantation. To examine its potential use for radioimmunotherapy, we developed an efficient and reproducible technical protocol for labelling anti-NCA antigen antibody BW 250/183 with generator-produced rhenium-188, aiming at both high radiochemical yield and high specific activity. 188Re-labelled BW 250/183 antibody was used in 12 patients with advanced leukaemia. Labelling of BW 250/183 with 188Re was accomplished by the direct radiolabelling method using tris-(2-carboxyethyl) phosphine (TCEP) as the reducing agent. Twelve patients with recurrent acute or chronic leukaemia were treated with activities of 6.5-12.4 GBq of 188Re-labelled BW 250/183. Standard gamma camera scintigraphy was used to evaluate the biodistribution, and a region of interest analysis together with the MIRDOSE 3.1 software was applied to determine the radiation doses to relevant tissues. The 188Re-BW 250/183 antibody was labelled in high radiochemical yield, with high radiochemical purity (94% ± 3%) and specific activity (5.55-7.4 GBq/mg) within 1 h. The preliminary biodistribution studies showed persistent uptake of 188Re-BW 250/183 in bone marrow. The radiation absorbed doses (mGy/MBq) delivered to the total body, red marrow, liver, spleen and kidneys were 0.13 ± 0.02, 1.45 ± 0.71, 0.43 ± 0.21, 1.32 ± 0.99 and 0.71 ± 0.17, respectively. TCEP reduction enabled the direct, fast and effective labelling of the monoclonal antibody BW 250/183 with 188Re. Preliminary clinical results suggest delivery of a significant radiation dose to bone marrow and thus the potential for adjuvant conditioning therapy before BMT.

Details

Original languageEnglish
Pages (from-to)1265-1273
Number of pages9
JournalEuropean Journal of Nuclear Medicine
Volume26
Issue number10
Publication statusPublished - 1999
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 10541824

Keywords

Keywords

  • Anti-NCA-95 antibody, Direct labelling, Leukaemia, Radioimmunotherapy, Rhenium-188