Therapy of rat tracheal carcinoma IC-12 in SCID mice

Vascular targeting with [213Bi]-MAb TES-23

Stephen Kennel, T. Lankford, S. Davern, L. Foote, K. Taniguchi, I. Ohizumi, Y. Tsutsumi, S. Nakagawa, T. Mayumi, S. Mirzadeh

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)1278-1287
Number of pages10
JournalEuropean Journal of Cancer
Volume38
Issue number9
DOIs
StatePublished - Jun 18 2002
Externally publishedYes

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SCID Mice
Blood Vessels
Monoclonal Antibodies
Carcinoma
Neoplasms
Therapeutics
Vascular Tissue Neoplasms
TES
Lung
Therapeutic Uses
Autoradiography
Radioisotopes
Radioactivity

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Therapy of rat tracheal carcinoma IC-12 in SCID mice : Vascular targeting with [213Bi]-MAb TES-23. / Kennel, Stephen; Lankford, T.; Davern, S.; Foote, L.; Taniguchi, K.; Ohizumi, I.; Tsutsumi, Y.; Nakagawa, S.; Mayumi, T.; Mirzadeh, S.

In: European Journal of Cancer, Vol. 38, No. 9, 18.06.2002, p. 1278-1287.

Research output: Contribution to journalArticle

Kennel, S, Lankford, T, Davern, S, Foote, L, Taniguchi, K, Ohizumi, I, Tsutsumi, Y, Nakagawa, S, Mayumi, T & Mirzadeh, S 2002, 'Therapy of rat tracheal carcinoma IC-12 in SCID mice: Vascular targeting with [213Bi]-MAb TES-23', European Journal of Cancer, vol. 38, no. 9, pp. 1278-1287. https://doi.org/10.1016/S0959-8049(02)00078-3
Kennel, Stephen ; Lankford, T. ; Davern, S. ; Foote, L. ; Taniguchi, K. ; Ohizumi, I. ; Tsutsumi, Y. ; Nakagawa, S. ; Mayumi, T. ; Mirzadeh, S. / Therapy of rat tracheal carcinoma IC-12 in SCID mice : Vascular targeting with [213Bi]-MAb TES-23. In: European Journal of Cancer. 2002 ; Vol. 38, No. 9. pp. 1278-1287.
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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.",
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T2 - Vascular targeting with [213Bi]-MAb TES-23

AU - Kennel, Stephen

AU - Lankford, T.

AU - Davern, S.

AU - Foote, L.

AU - Taniguchi, K.

AU - Ohizumi, I.

AU - Tsutsumi, Y.

AU - Nakagawa, S.

AU - Mayumi, T.

AU - Mirzadeh, S.

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