In this paper, the use of 123 I-Annexin V for the detection of farnesyltransferase inhibitor (FTI)-induced apoptosis in tumour-bearing athymic mice is described. In vitro binding assays on LoVo cells show time- and dosage-dependent I-125-Annexin V binding upon treatment with Tipifarnib (Zamestra, R115777), a selective and potent FTI. In vivo experiments using planar gamma scintigraphy oil LoVo inoculated mice show a 40% increased I-123-Annexin V uptake 8 h after a single oral administration of 100 mg/kg Tipifarnib in 20% beta-cyclodextrin in 0.1 M HCl, as well as after 3 days of twice daily treatments with the same dose. Ex vivo TUNEL assays, detecting end-stage apoptotic cells, correlate significantly with both in vitro and in vivo results. The percentage of necrosis is also increased by Tipifarnib treatment, but is too low to interfere Nvith the I-123-Annexin V uptake. It can be concluded that I-123-Annexin V can be used to nionitor Tipifarnib-induced apoptosis in LoVo xenograft tumours in athymic mice. Future applications might include the early prediction of FTI response and the selection of FTI-sensitive patients very shortly after treatment initiation. Subsequently, such patients Would greatly benefit from a noninvasive and fast therapy evaluation. (c) 2005 Elsevier Inc. All rights reserved.

Cornelissen, B., Lahorte, C., Kersemans, V., Capriotti, G., Bonanno, E., Signore, A., et al. (2005). In vivo apoptosis detection with radioiodinated Annexin V in LoVo tumour-bearing mice following Tipifarnib (Zarnestra, R115777) farnesyltransferase inhibitor therapy. NUCLEAR MEDICINE AND BIOLOGY, 32(3), 233-239 [10.1016/j.nucmedbio.2005.01.001].

In vivo apoptosis detection with radioiodinated Annexin V in LoVo tumour-bearing mice following Tipifarnib (Zarnestra, R115777) farnesyltransferase inhibitor therapy

BONANNO, ELENA;
2005

Abstract

In this paper, the use of 123 I-Annexin V for the detection of farnesyltransferase inhibitor (FTI)-induced apoptosis in tumour-bearing athymic mice is described. In vitro binding assays on LoVo cells show time- and dosage-dependent I-125-Annexin V binding upon treatment with Tipifarnib (Zamestra, R115777), a selective and potent FTI. In vivo experiments using planar gamma scintigraphy oil LoVo inoculated mice show a 40% increased I-123-Annexin V uptake 8 h after a single oral administration of 100 mg/kg Tipifarnib in 20% beta-cyclodextrin in 0.1 M HCl, as well as after 3 days of twice daily treatments with the same dose. Ex vivo TUNEL assays, detecting end-stage apoptotic cells, correlate significantly with both in vitro and in vivo results. The percentage of necrosis is also increased by Tipifarnib treatment, but is too low to interfere Nvith the I-123-Annexin V uptake. It can be concluded that I-123-Annexin V can be used to nionitor Tipifarnib-induced apoptosis in LoVo xenograft tumours in athymic mice. Future applications might include the early prediction of FTI response and the selection of FTI-sensitive patients very shortly after treatment initiation. Subsequently, such patients Would greatly benefit from a noninvasive and fast therapy evaluation. (c) 2005 Elsevier Inc. All rights reserved.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/08 - Anatomia Patologica
English
Annexin V; Apoptosis; Farnesyl transferase inhibitor; Oncology; Tipifarnib
Cornelissen, B., Lahorte, C., Kersemans, V., Capriotti, G., Bonanno, E., Signore, A., et al. (2005). In vivo apoptosis detection with radioiodinated Annexin V in LoVo tumour-bearing mice following Tipifarnib (Zarnestra, R115777) farnesyltransferase inhibitor therapy. NUCLEAR MEDICINE AND BIOLOGY, 32(3), 233-239 [10.1016/j.nucmedbio.2005.01.001].
Cornelissen, B; Lahorte, C; Kersemans, V; Capriotti, G; Bonanno, E; Signore, A; Van De, W; C, ; Dierckx, R; Slegers, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/32394
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