Dynamic coupling of Tc-99m-MIBI efflux and apoptotic pathway activation in untreated breast cancer patients(483 views) Del Vecchio S, Zannetti A, Ciarmiello A, Aloj L, Caracò C, Fonti R, Botti G, D'Aiuto G, Salvatore M
Keywords: 99mtc-Mibi Efflux, Apoptosis, Breast Cancer, Multidrug Resistance, Glycoprotein P, Methoxy Isobutyl Isonitrile Technetium Tc 99m, Diagnostic Agent, Radiopharmaceutical Agent, Tumor Marker, Dna Fragment, Monoclonal Antibody Ki 67, Adult, Article, Cell Proliferation, Clinical Article, Controlled Study, Correlation Analysis, Female, Human, Human Tissue, Imaging, Mitochondrion, Nick End Labeling, Tumor Cell, Biological Model, Breast Tumor, Lung Carcinoma, Metabolic Clearance Rate, Middle Aged, Paget Nipple Disease, Pathology, Scintiscanning, Tumor Recurrence, Cell Activation, Chemical Labeling, Human Cell, Inhibition Kinetics, Protein Function, Protein Transport, Signal Transduction, 80 And Over, Breast Neoplasms, Lobular, Neoplasm Recurrence, Local, P-Glycoprotein, Technetium Tc 99m Sestamibi,
Affiliations: *** IBB - CNR ***
Nuclear Medicine Center of the National Research Council (CNR), Department of Biomorphological, Functional Sciences University Federico II, Via S. Pansini, 5, 80131 Naples, Italy
National Cancer Institute, Via M. Semmola, Naples, Italy
Institute of Experimental Medicine and Biotechnologies, CNR, Piano Lago Mangone, Cosenza, Italy
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Dynamic coupling of Tc-99m-MIBI efflux and apoptotic pathway activation in untreated breast cancer patients
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, P< 0. 0001). The efflux rate of 99mTc-MIBI was directly and significantly correlated with the apoptotic index (r=0. 74, P< 0. 0001) and with the rate of proliferation (r=0. 58, P< 0. 001). After partial correlation analysis, only the apoptotic index showed a significant correlation with the efflux rate of 99mTc-MIBI (r=0. 57, P< 0. 001). Our findings indicate that enhanced transport activity of Pgp is associated with increased activation of the apoptotic pathway, suggesting that inhibition of Pgp function with specific modulators may be effective in these patients. Furthermore, since mitochondria are central executioners of apoptosis and intracellular sites of 99mTc-MIBI sequestration, a model for the dynamic coupling of Pgp-dependent 99mTc-MIBI efflux and apoptotic pathway activation may be derived
Dynamic coupling of Tc-99m-MIBI efflux and apoptotic pathway activation in untreated breast cancer patients
Cusanno F, Cisbani E, Colilli S, Fratoni R, Garibaldi F, Giuliani F, Gricia M, Lucentini M, Magliozzi ML, Santarivenere F, Torrioli S, Cinti MN, Pani R, Pellegrini R, Simonetti G, Schillaci O, Del Vecchio S, Salvatore M, Majewski S, De Vincentis G, Scopinaro F * Results of clinical trials with SPEM(278 views) Nucl Instrum Methods Phys Res Sect A, 2007 Feb 1; 497(1): 46-50. Impact Factor:3.221 ViewExport to BibTeXExport to EndNote
Hesse B, Tagil K, Cuocolo A, Anagnostopoulos C, Bardies M, Bax J, Bengel F, Busemann Sokole E, Davies G, Dondi M, Edenbrandt L, Franken P, Kjaer A, Knuuti J, Lassmann M, Ljungberg M, Marcassa C, Marie PY, Mckiddie F, O'connor M, Prvuolovich E, Underwood R * 3. 0 T perfusion MR imaging(730 views) Rivista Di Neuroradiologia (ISSN: 1120-9976), 2004; 17(6): 807-812. Impact Factor:0.023 ViewExport to BibTeXExport to EndNote