Abstract
The uptake and washout kinetics of two cationic lipophilic99mTc-labeled myocardial perfusion agents,99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and99mTc-l,2-bis[bis-(2-ethoxyethyl)-phosphino]ethane (99mTc-Tetrofosmin), were studied in cultured smooth muscle cells and compared to the conventional myocardial perfusion agent,201Tl. Both99mTc-MIBI and99mTc-Tetrofosmin had a 4-fold greater uptake than201Tl, and they were washed out of cells through similar kinetics which had slower rates than201T1. Incubation with metabolism inhibitors had a modest influence on the uptake of these two99mTc-labeled agents, although their extent and inhibited sites were slightly different. Ion transport inhibitors did not affect the uptake of99mTc-MIBI, although the99mTc-Tetrofosmin uptake was slightly inhibited when the Ca2+ channel was blocked. Our studies indicate that99mTc-MIBI and99mTc-Tetrofosmin were taken up by smooth muscle cells in similar pharmacokinetic patterns, but their accumulation reflected a different meaning for cell viability.
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Kubo A, Nakamura K, Sammiya T, Shimizu S, Hashimoto S, Iwanaga S, et al. Phase I clinical study of99mTc-MIBI.KAKU IGAKU (Jpn J Nucl Med) 28: 1133–1142, 1991.
Wackers FJT, Berman DS, Maddahi J, Watson DD, Beller GA, Strauss HW, et al. Technetium-99m hexakis 2-methoxyisobutyl isonitrile: Human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging.J Nucl Med 30: 301–310, 1989.
Sands H, Delano ML, Gallaghe BM. Uptake of hexakis (tbutylisonitrile) technetium(I) and hexakis-(isopropylisonitrile) technetium(I) by neonatal rat myocytes and human erythrocytes.J Nucl Med 27: 404–408, 1986.
Chiu ML, Herman ZW, Kronauge JF, Piwnica-Worms D. Comparative effects of neutral dipolar compounds and lipophilic anions on Technetium-99m-hexakis(2-methoxyisobutyl isonitrile) accumulation in cultured chick ventricular myocytes.Invest Radiol 27: 1052–1058, 1992.
Maublant JC, Moins N, Gachon P, Renoux M, Zhang Z, Veyre A. Uptake of Technetium-99-teboroxime in cultured myocardial cells: Comparison with Thallium-201 and Technetium-99m-sestamibi.J Nucl Med 34: 255–259, 1993.
Piwnica-Worms D, Chiu ML, Kronauge JF. Divergent kinetics of201Tl and99mTc-SESTAMIBI in cultured chick ventricular myocytes during ATP depletion.Circulation 85: 1531–1541, 1992.
Piwnica-Worms D, Chiu ML, Knonauge JF. Detection of adriamycin-induced cardiotoxicity in cultured heart cells with technetium-99m-SESTAMIBI.Cancer Chemother Pharmacol 32: 385–391, 1993.
Crane P, Laliberte R, Heminway S, Thoolen M, Orlandi C. Effect of mitochondrial viability and metabolism of technetium-99m-sestamibi myocardial retention.Eur J Nucl Med 20: 20–25, 1993.
Kronauge JF, Chiu ML, Cone JS, Davison A, Holaman BL, Jones AG, et al. Comparison of neutral and cationic myocardial perfusion agents: Characterization of accumulation in cultured cells.Nucl Med Biol 19: 141–148, 1992.
Cordobes MD, Starzec A, Delmon-Moingeon L, Blanchot C, Kouyoumdjian J-C, Prevost G, et al. Technetium-99msestamibi uptake by human benign and malignant breast tumor cells: Correlation withmdr gene expression.J Nucl Med 37: 286–289, 1996.
Delmon-Moingeon LI, Piwnica-Worms D, Abbeele AD Vd, Holman BL, Davidson A, et al. Uptake of the cation hexaxis(2-methoxyisobutylisonitrile)-technetiurn-99m by human carcinoma cell inesin vitro.Cancer Research 50: 2198–2202, 1990.
Piwnica-Worms D, Rao CV, Kronauge JF, Croop JM. Characterization of multidrug resistance P-glycoprotein transport function with an organotechnetium cation.Biochemistry 34: 12210–12220, 1995.
Ballinger JR, Huan HN, Berry BW, Boxon I.99mTc-sestamibi as an agent for imaging P-glycoprotein-mediated in a rat breast tumor cell line and its doxorubicin-resistant variant.Nucl Med Commun 16: 253–257, 1995.
Rao VV, Chiu ML, Kronauge JF, Piwnica-Worms D. Expression of recombinant human multidrug resistance Pglycoprotein in insect cells confers decreased accumulation of technetium-99m-sestamibi.J Nucl Med 35: 510–515, 1994.
Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM. Functional imaging of multidrugresistant P-glycoprotein with an organotechnetium complex.Cancer Research 53: 977–984, 1993.
Komori T, Matsui R, Adachi I, Shimizu T, Sueyoshi K, Narabayashi I.In vitro uptake and release of201T1 and99mTc-MIBI in HeLa cell.KAKU IGAKU (Jpn J Nucl Med) 32: 651–658, 1995.
Sutter CW, Joshi MJ, Stadalnik RC. Noncardiac uptake of technetium-99m MIBI.Seminars in Nuclear Medicine 24: 84–86, 1994.
Platts EA, North TL, Pickett RD, Kelly JD. Mechanism of uptake of technetium-tetrofosmin I. Uptake into isolated adult rat ventricular myocytes and subcellular localization.J Nucl Cardiol 2: 317–326, 1995.
Kubo A, Nakamura K, Hashimoto J, Sammiya T, Iwanaga S, Hashimoto S, et al. Phase I Clinical Trial of a new myocardial imaging agent,99mTc-PPN1011.KAKU IGAKU (Jpn J Nucl Med) 29: 1165–1176, 1992.
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Nakamura, K., Sammiya, T., Hashimoto, J. et al. Comparison of cationic myocardial perfusion agents: Characteristics of accumulation in cultured smooth muscle cells. Ann Nucl Med 10, 375–381 (1996). https://doi.org/10.1007/BF03164797
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DOI: https://doi.org/10.1007/BF03164797