Dynamic coupling of 99mTc-MIBI efflux and apoptotic pathway activation in untreated breast cancer patients

Silvana Del Vecchio, Antonella Zannetti, Andrea Ciarmiello, Luigi Aloj, Corradina Caracò, Rosa Fonti, Gerardo Botti, Giuseppe D'Aiuto, Marco Salvatore

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Our previous studies showed that the efflux rate of technetium-99m methoxyisobutylisonitrile (MIBI) is directly correlated to P-glycoprotein (Pgp) levels in breast carcinoma. The aim of this study was to test whether the Pgp-dependent efflux of 99mTc-MIBI is related to the apoptotic pathway activation in breast carcinoma. Thirty-three untreated non-consecutive patients were intravenously injected with 740 MBq 99mTc-MIBI and serial images were obtained up to 4 h. The rate of efflux was determined by mono-exponential fitting of decay-corrected time-activity curves. Tumour specimens were then obtained at surgery and processed for the determination of the apoptotic index by in situ end-labelling of DNA fragments (Tunel). The rate of tumour cell proliferation was also determined using Ki67 monoclonal antibody. All breast carcinomas showed focal uptake of 99mTc-MIBI and the time to half clearance varied between 85 and 574 min. The apoptotic index ranged between 0.3% and 4.2%, whereas the rate of proliferation varied between 13% and 40%. We found a positive and significant correlation between the apoptotic index and the rate of proliferation (r=0.79, P99mTc-MIBI was directly and significantly correlated with the apoptotic index (r=0.74, P99mTc-MIBI (r=0.57, P99mTc-MIBI sequestration, a model for the dynamic coupling of Pgp-dependent 99mTc-MIBI efflux and apoptotic pathway activation may be derived.

Original languageEnglish
Pages (from-to)809-814
Number of pages6
JournalEuropean Journal Of Nuclear Medicine
Issue number6
Publication statusPublished - 2002


  • Tc-MIBI efflux
  • Apoptosis
  • Breast cancer
  • Multidrug resistance

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology


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