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

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 languageEnglish
Pages (from-to)879-887
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume30
Issue number6
Publication statusPublished - Jun 1 2003

Fingerprint

Apoptosis Regulatory Proteins
Breast Neoplasms
Neoplasms
Carcinoma
Drug Therapy
bcl-2-Associated X Protein
Prone Position
Mitochondrial Membrane Potential
Mitochondria
Radiotherapy
Inhibition (Psychology)
Apoptosis
Injections
Proteins

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 journalArticle

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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.",
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