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, P99mTc-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.
Original language | English |
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Pages (from-to) | 879-887 |
Number of pages | 9 |
Journal | European Journal of Nuclear Medicine and Molecular Imaging |
Volume | 30 |
Issue number | 6 |
Publication status | Published - Jun 1 2003 |
Keywords
- Tc-MIBI
- Apoptosis
- Bcl-2
- Breast cancer
- Resistance
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Radiological and Ultrasound Technology