Keywords: 99mtc-Mibi, Apoptosis, Breast Cancer, Multidrug Resistance, P-Glycoprotein, Antineoplastic Agent, Glycoprotein P Inhibitor, Methoxy Isobutyl Isonitrile Technetium Tc 99m, Protein Bcl 2, Tetrofosmin Tc 99m, Cancer Adjuvant Therapy, Cancer Cell, Conference Paper, Correlation Analysis, Drug Accumulation, Drug Clearance, Drug Uptake, Human, Imaging System, Mitochondrion, Patient Identification, Prognosis, Protein Expression, Treatment Failure, Treatment Response,
Affiliations: *** IBB - CNR ***
Institute of Biostructures and Biomages, National Research Council (CNR), Naples, Italy
Department of Biomorphological and Functional Sciences, University Federico II, Naples, Italy
Istituto di Biostrutture e Bioimmagini, Cnr, Edificio 10, Via S. Pansini, 5, I 80131 Naples, Italy
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Gottesman, M. M., Fojo, T., Bates, S. E., Multidrug resistance in cancer: Role of ATP-dependent transporters (2002) Nat Rev Cancer, 2, pp. 48-5
Carvalho, P. A., Chiu, M. L., Kronauge, J. F., Kawamura, M., Jones, A. G., Holman, B. L., Piwnica-Worms, D., Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts (1992) J Nucl Med, 33, pp. 1516-1522
Crankshaw, C. L., Marmion, M., Luker, G. D., Rao, V., Dahlheimer, J., Burleigh, B. D., Webb, E., Piwnica-Worms, D., Novel technetium (III) -Q complexes for functional imaging of multidrug resistance (MDR1) P-glycoprotein (1998) J Nucl Med, 39, pp. 77-86
Ballinger, J. R., Bannerman, J., Boxen, I., Firby, P., Hartman, N. G., Moore, M. J., Technetium-99m-tetrofosmin as a substrate for P-glycoprotein: In vitro studies in multidrug-resistant breast tumor cells (1996) J Nucl Med, 37, pp. 1578-1582
Ballinger, J. R., Muzzammil, T., Moore, M. J., Technetium 99m-furifosmin as an agent for functional imaging of multidrug resistance in tumors (1997) J Nucl Med, 38, pp. 1915-1919
Hendrikse, N. H., Franssen, E. J., van der Graaf, W. T., Vaalburg, W., de Vries, E. G., Visualization of multidrug resistance in vivo (1999) Eur J Nucl Med, 26, pp. 283-293
Trock, B. J., Leonessa, F., Clarke, R., Multidrug resistance in breast cancer: A meta-analysis of MDR1/gp170 expression and its possible functional significance (1997) J Natl Cancer Inst, 89, pp. 917-931
Igney, F. H., Krammer, P. H., Death and anti-death: Tumour resistance to apoptosis (2002) Nat Rev Cancer, 2, pp. 277-288
Functional imaging of multidrug resistance in breast cancer
Intrinsic or acquired multidrug resistance is the major cause of treatment failure in many human cancers. Multiple cellular mechanisms may contribute to the development of multidrug resistance including overexpression of P-glycoprotein (Pgp). The use of 99mTc-labeled lipophilic cations, which are transport substrate of Pgp, raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. Among these agents, 99mTc-MIBI is the most widely evaluated tracer and may serve as a paradigm of this class of compounds. In particular, many studies have shown the prognostic value of 99mTc-MIBI scan in different types of malignancy including breast cancer and the correlation with the expression of Pgp. However, additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may also affect 99mTc-MIBI uptake in tumors. In particular, overexpression of the anti-apoptotic protein Bcl-2 prevents tumor cells to enter apoptosis and inhibits tracer accumulation into mitochondria. Therefore, while an absent or reduced early tracer uptake in large breast carcinomas reflects the existence of a defective apoptotic program, an enhanced tracer clearance in 99mTc-MIBI positive lesions reflects the activity of drug transporters such as Pgp. The existence of two different mechanisms underlying the predictive role of 99mTc-MIBI scan may be important to establish whether individual patients may benefit from Pgp inhibitors or Bcl-2 antagonists.
Functional imaging of multidrug resistance in breast cancer
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(284 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote
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