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 |
|---|---|
| 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 |
Fingerprint
Keywords
- Tc-MIBI
- Apoptosis
- Bcl-2
- Breast cancer
- Resistance
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Radiological and Ultrasound Technology
Cite this
Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma. / Del Vecchio, Silvana; Zannetti, Antonella; Aloj, Luigi; Caracò, Corradina; Ciarmiello, Andrea; Salvatore, Marco.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 30, No. 6, 01.06.2003, p. 879-887.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma
AU - Del Vecchio, Silvana
AU - Zannetti, Antonella
AU - Aloj, Luigi
AU - Caracò, Corradina
AU - Ciarmiello, Andrea
AU - Salvatore, Marco
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
KW - Tc-MIBI
KW - Apoptosis
KW - Bcl-2
KW - Breast cancer
KW - Resistance
UR - http://www.scopus.com/inward/record.url?scp=0038714411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038714411&partnerID=8YFLogxK
M3 - Article
C2 - 12721767
AN - SCOPUS:0038714411
VL - 30
SP - 879
EP - 887
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 6
ER -