Abstract
In previous work, we have demonstrated that vascular targeting of [213Bi], an α-emitter, to lung blood vessels could efficiently destroy tumour colonies growing in the lung. In order to expand this approach to treatment of tumours growing in other sites, we employed the monoclonal antibody (MAb) TES-23, which reacts with CD44H, preferentially expressed on new blood vessels in tumours. Biodistribution studies of N-succinimidyl [125I] 3-iodobenzoate (SIB)-radiolabelled MAb TES-23 in ICR-severe combined immunodeficient (SCID) mice bearing subcutaneous (s.c.) and intramuscular (i.m.) IC-12 tumours, demonstrated efficient tumour uptake. At 24 h, accumulation in small tumours was 45%ID/g for s.c. tumours, and 58%ID/g for i.m. tumours and in large tumours it was 25%ID/g for s.c. tumours and 17%ID/g for i.m. tumours. Micro-autoradiography data confirmed that radiolabel accumulated in or near tumour blood vessels. Normal tissues had very low levels of radioactivity. Treatment of mice bearing small IC-12 tumours with [213Bi] MAb TES-23 retarded tumour growth relative to animals treated with cold MAb TES-23. Biodistribution and therapy experiments were also performed in BALB/c mice bearing both s.c. and i.m. syngeneic, lung carcinoma (line 498) tumours. [I125] SIB MAb TES-23 accumulated efficiently in both s.c. and i.m. tumours (14%ID/g and 15%ID/g, respectively, at 4 h); however, no therapeutic effect of [213Bi] MAb TES-23 treatment could be demonstrated in this model system. The data demonstrate that the timing of vascularisation of the tumours and the delivery kinetics of MAb relative to the half-life of the therapeutic radionuclide are critical for effective therapy.
Original language | English |
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Pages (from-to) | 1278-1287 |
Number of pages | 10 |
Journal | European Journal of Cancer |
Volume | 38 |
Issue number | 9 |
DOIs | |
State | Published - 2002 |
Funding
The authors thank Arnold Beets for technical assistance. Jim Wesley of Ridge Microtome prepared the sections and performed the autoradiography. Drs Russ Knapp and Brynn Jones were helpful in review of the manuscript. This work was supported by the Department of Energy, Medical Sciences Division, through funding designation ERKP 038. The Oak Ridge National Laboratory is managed by UT-Battelle, LLC, for the US Department of Energy under contract DE-AC05-00OR22725. The submitted manuscript has been authored by a contractor of the US Government under contract DE-AC005-00OR22725. Accordingly, the US Government retains a non-exclusive, royalty-free licence to publish or reproduce the published form of this contribution, or allow others to do so, for US Government purposes.
Keywords
- SCID mice
- TES-23, [Bi]
- Therapy
- Vascular targeting