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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2003 | Original Article

Inhibition of early ^99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma

Authors: Silvana Del Vecchio, Antonella Zannetti, Luigi Aloj, Corradina Caracò, Andrea Ciarmiello, Marco Salvatore

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2003

Abstract

Lack of technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) uptake is consistently reported to predict poor response to subsequent chemotherapy in a variety of human malignant tumours. Since ^99mTc-MIBI accumulates within mitochondria, which also play a central role in apoptosis through the integration of death signals by Bcl-2 family members, we tested whether early ^99mTc-MIBI uptake is affected by alterations of the apoptotic pathway. Forty-two breast cancer patients were intravenously injected with 740 MBq of ^99mTc-MIBI and planar images were obtained 10 min post injection with the patients in the prone lateral position. Ten carcinomas failed to accumulate ^99mTc-MIBI and could not be visualised on scintigraphic images despite being larger than 1.8 cm (MIBI negative). Thirty-two of the 42 breast carcinomas showed focal uptake of ^99mTc-MIBI (MIBI positive), and 10 min tumour-to-background ratios (T/B) varied between 1.14 and 6.93. The apoptotic index, the rate of proliferation, and the expression of the anti-apoptotic Bcl-2 protein and pro-apoptotic Bax protein were assessed in surgically excised tumours. All MIBI-negative carcinomas showed a dramatic and statistically significant reduction in the apoptotic index as compared with MIBI-positive lesions (mean±SD, 0.14±0.15 vs 1.28±0.83, P<0.0001) independently of rate of proliferation, tumour size and P-glycoprotein expression. Significantly higher levels of Bcl-2 were also found in MIBI-negative as compared with MIBI-positive carcinomas. In MIBI-positive lesions, an inverse significant correlation was found between T/B ratios and Bcl-2 levels (r=−0.50, P<0.01). Our findings indicate that early uptake of ^99mTc-MIBI in breast carcinomas is affected by alterations of apoptotic pathway. High levels of Bcl-2, despite the stabilisation of mitochondrial membrane potentials, prevent accumulation of ^99mTc-MIBI in tumour cells. In conclusion, absent or reduced early ^99mTc-MIBI uptake in large tumours may indicate a Bcl-2-mediated resistance to chemo- and radiotherapy.

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Title: Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma
Authors: Silvana Del Vecchio
Antonella Zannetti
Luigi Aloj
Corradina Caracò
Andrea Ciarmiello
Marco Salvatore
Publication date: 01-06-2003
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2003
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-003-1161-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Inhibition of early ^99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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