Mechanism of uptake of technetium-tetrofosmin. II: Uptake into isolated adult rat heart mitochondria

Younès, Antoine; Songadele, Jean Arthur; Maublant, J.; Platts, Elizabeth; Pickett, R. D.; Veyre, A.

doi:10.1016/s1071-3581(05)80077-7

Cited by 92 publications

(54 citation statements)

References 13 publications

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“…This is strikingly similar to the known mechanism of cationic [ 99m Tc]sestamibi and [ 99m Tc] tetrofosmin accumulation and retention based on the potential gradient sustained in viable mitochondria. [30][31][32] The high concentration of mitochondria in the heart tissue provides a reservoir for the flow tracers.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial avid radioprobes. Preparation and evaluation of 7′(Z)-[125I]iodorotenone and 7′(Z)-[125I]iodorotenol

VanBrocklin

Hanrahan

Enas

et al. 2007

Nuclear Medicine and Biology

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The loss of mitochondrial function has been implicated in a number of maladies such as Huntington's Disease, Parkinson's Disease, cancer and cardiovascular disease. The objective of this research was to develop a radiolabeled mitochondrial probe. Two tracers, 7′-Z-iodorotenol and 7′-Z-iodorotenone, analogs of rotenone a natural product that inhibits Complex I of the mitochondrial electron transport chain, have been labeled with iodine-125 in 45-85% yield in a single step from the corresponding tribuytylstannyl precursor. In vivo distribution in adult male Sprague-Dawley rats for both compounds showed high accumulation in the heart (1.7-3.7 %ID/g at 1h), a tissue with high mitochondrial content. Z-Iodorotenol did not washout of most tissues between 1 and 2 h post injection whereas Z-iodorotenone showed moderate washout (7-26%) over the same period. By 24 h there was significant loss of both compounds from most tissues including the heart. Heart-to-blood, -lung and -liver ratios for Z-iodorotenone of 28.9, 10.7 and 2.4, respectively, were two-to four-fold higher than the Z-iodorotenol ratios. Compared to the current clinical perfusion tracers, 99m Tc-sestamibi and 99m Tc-tetrofosmin, Z-iodorotenone demonstrates similar 1h heart accumulation and significantly higher heart-to-lung ratio (P <0.001). Z-Iodorotenone heart-to-liver ratio is equivalent to 99m Tcsestamibi. 7′-Z-Iodorotenone possesses distribution characteristics of an improved tracer for SPECT perfusion studies.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial avid radioprobes. Preparation and evaluation of 7′(Z)-[125I]iodorotenone and 7′(Z)-[125I]iodorotenol

VanBrocklin

Hanrahan

Enas

et al. 2007

Nuclear Medicine and Biology

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“…[19][20][21] In patients with AMI who underwent reperfusion therapy, the RR phenomenon has been demonstrated on 99m Tc-labeled flow tracers myocardial scintigraphy and the myocardium that shows the RR phenomenon of 99m Tc-labeled flow tracers is thought to be damaged, though contractile function is preserved to a certain extent. [7][8][9] Sugihara et al 7 reported that the impairment of the LV wall motion in the regions showing the 99m Tc-tetrofosmin RR phenomenon, evaluated using contrast left ventriculography, ranged from akinesis/dyskinesis to normal, but was significantly better than that in the regions with a fixed defect.…”

Section: Reverse Redistribution Phenomenon Of 99m Tc-tetrofosminmentioning

confidence: 99%

Reverse Redistribution Phenomenon on Rest 99mTc-Tetrofosmin Myocardial Single Photon Emission Computed Tomography Involves Impaired Left Ventricular Contraction in Patients With Acute Myocardial Infarction

Kurokawa

Ohte

Miyabe

et al. 2003

Circ J

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yocardial perfusion scintigraphy using as the flow tracer has been widely applied for the evaluation of myocardial ischemia and viability in patients with myocardial infarction. 1 Simultaneous evaluation of left ventricular (LV) wall motion and LV myocardial perfusion provides more information for this purpose, but as 201 Tl is not suitable as the tracer for electrocardiograph (ECG)-gated single photon emission computed tomography (SPECT), which is used for elucidating LV wall motion, echocardiography and/or left ventriculography have been the alternative techniques. 2,3 However, using a technetium (Tc)-labeled myocardial perfusion tracer, technetium-99m ( 99m Tc)-tetrofosmin, as well as 99m Tc-sestamibi allows simultaneous assessment of myocardial perfusion and LV function by ECG-gated SPECT because once these tracers are taken up by the myocardium, then the clearance is relatively slow and redistribution does not occur for several hours. [4][5][6] Several investigators have reported that in patients with acute myocardial infarction (AMI) after reperfusion therapy, myocardial imaging with 99m Tc-tetrofosmin or 99m Tcsestamibi shows a reverse redistribution (RR) phenomenon, 7-9 similar to that observed on 201 Tl scintigraphy in such patients. [10][11][12][13][14][15] The clinical significance of the RR of 201 Tl has been vigorously investigated, 10-15 compared with that on 99m Tc-tetrofosmin scintigraphy, which has not been fully elucidated. Thus, we used ECG-gated myocardial SPECT to investigate this issue in patients with AMI from the viewpoint of LV wall thickening after exercise. Methods PatientsWe studied 25 consecutive patients (17 men, 8 women, age 48-80 years) with AMI who underwent 99m Tc-tetrofosmin myocardial SPECT at rest approximately 3 weeks after the onset of infarction. Patients who had a prior myocardial infarction and/or coronary artery bypass surgery were excluded from the study. All the study patients underwent exercise stress ECG-gated SPECT with 99m Tc-tetrofosmin within 1 week of the rest study, and then selective coronary angiography was carried out. In those patients who did not Circ J 2003; 67: 830 -834 (Received February 10, 2003; revised manuscript received June 9, 2003; accepted July 9, 2003 The purpose of this study was to investigate the clinical significance of the reverse redistribution (RR) phenomenon on technetium-99m ( 99m Tc)-tetrofosmin myocardial single photon emission computed tomography (SPECT) performed at rest. Twenty-five patients underwent myocardial SPECT 3 weeks after the onset of acute myocardial infarction. Myocardial images were acquired at 40 min (early) and 4 h (delayed) after the injection of 740 MBq of 99m Tc-tetrofosmin. The regional myocardial uptake of the tracer in 26 segments of the left ventricular (LV) wall was visually scored from 0 (no activity) to 3 (normal activity), and then the RR was defined as a decrease of more than 1 point in the activity score on the delayed image compared with that on the early image. Regions with an activity score of...

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“…26,27 Kresnik et al 8 reported decreased tetrofosmin uptake in patients with degenerative goiter and HT in a late scan obtained at 1 h after injection. In other study, Younes et al 25 showed that the mechanism of tetrofosmin uptake was dependent on the amount of mitochondrial proteins using cell-based systems. Based on the data from Younes's report, 25 Kresnik et al 8 suggested that the decrease or loss of uptake capability in thyroid tissue was due to degenerative changes.…”

Section: Fi Gu Rementioning

confidence: 98%

“…Thus, we suggest that the changes in 99m Tc-tetrofosmin kinetics in thyroid tissue parallels the degree of thyrocyte destruction in HT. Tetrofosmin is a perfusion agent, 25 and is an indicator of cell viability. 26,27 Kresnik et al 8 reported decreased tetrofosmin uptake in patients with degenerative goiter and HT in a late scan obtained at 1 h after injection.…”

Section: Fi Gu Rementioning

confidence: 99%

Changes of Thyroidal Tc-99m Tetrofosmin Uptake and Wash-Out in Patients with Hashimoto’s Thyroiditis

Yüksel¹,

Fenkci²,

Kıraç³

et al. 2010

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Our aim was to in ves ti ga te the chan ges in Tc-99m tet ro fos min up ta ke and wash-out in the thyro id gland of nor mal vo lun te ers and Has hi mo to's thyro i di tis (HT) pa tients with eit her euth yro i dism or hypoth yro i dism. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Thirty-fo ur pa ti ents with HT (10 hypoth yro id and 24 euth yro id) and 10 euth yro id he althy vo lun te ers we re en rol led in the study. In all ca ses, thyroid stimulating hormone (TSH), fre e thyro xi ne (FT4), fre e tri i odoth yro ni ne (FT3), an ti-thyro id an ti bo di es and thyro id vo lu me we re me a su red. An te ri or thyroid ima ges we re ac qu i red at 10, 30 and 120 min af ter in tra ve no us in jec ti on of 740 MBq Tc-99m tet ro fos min. Thyro id/ back gro und (T/B) ra ti os at 10, 30 and 120 min and wash-out in di ces (WI %) at 30 and 120 min we re cal cu la ted. R Re e s su ul lt ts s: : In all gro ups, ini ti al and la te tet ro fos min T/B va lu es did not dif fer from he althy con trol ca ses. At 120 min, the me an WI% of pa ti ents with hypothyro i dism was sig ni fi cantly hig her than that of vo lun te ers; ho we ver this gro up is not sta tis ti cally dif fe rent from the euth yro id gro up. The va lu e WI % at 120 min was sig ni fi cantly cor re la ted with an ti-Tg an ti body le vels (r= -0.673; p= 0.033). In the euth yro id gro up, both an ti-TPO an ti body le vels and thyro id vo lu me had sig ni fi cant cor re la ti ons with the T/B ra ti os at 10, 30 and 120 min (r= 0.499, p= 0.013; r= 0.424, p= 0.039; r=0.528, p= 0.008 for An ti-TPO An ti body, and r= 0.577, p= 0.003; r= 0.606, p= 0.002; r= 0.645, p= 0.010, for thyro id vo lu me, res pec ti vely). C Co on nc c l lu u s si i o on n: : We can conc lu de that Tc-99m tet ro fos min up ta ke and wash-out ki ne tics in thyro id tis su e may be chan ged with au to im mu ne thyrocy te des truc ti on in HT.K Ke ey y W Wo or rd ds s: : Tech ne ti um Tc 99m tetrofosmin; Has hi mo to di se a se; ra di o nuc li de ima ging Ö ÖZ ZE ET T A Am ma aç ç: : Ama cı mız öti ri o i dizm ve ya hi po ti ro i dizm li Has hi mo to Ti ro i dit li (HT) has ta la rın ve sağ lık lı gö nül lü le rin ti ro id be zin de ki Tc-99m tet ro fos min tu tu lum ve atı lı mın da ki de ği şik lik le ri araş tır mak tı. G Ge e r re eç ç v ve e Y Yö ön n t te em ml le er r: : Has hi mo to Ti ro i dit li 34 has ta (10'u hi po ti ro id ve 24'ü öti ro id) ve 10 öti ro id sağ lık lı gö nül lü ça lış ma ya alın dı. Tüm ol gu la rın tiroid stimule edici hormon (TSH), serbest ti rok sin (FT4), ser best tri i yo do ti ro nin (FT3), an ti-ti ro id an ti kor dü zey le ri ve ti ro id ha cim le ri öl çül dü. İntra ve nöz ola rak 740 MBq Tc-99m tet ro fos min en jek si yo nun dan son ra 10, 30 ve 120 daki ka lar da an te ri or ti ro id gö rün tü le ri alın dı. Bu gö rün tü ler den 10, 30, 120 dk ti ro id/ze min ak ti vi te (T/B) oran la rı ve 30 ve 120 da ki ka da ki "wash-ou t" in deks le ri (%WI) he sap lan dı. B Bu ul l g gu u ...

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Mechanism of uptake of technetium-tetrofosmin. II: Uptake into isolated adult rat heart mitochondria

Abstract: It was concluded that the accumulation of 99mTc-labeled tetrofosmin by the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential.

Cited by 92 publications

References 13 publications

Mitochondrial avid radioprobes. Preparation and evaluation of 7′(Z)-[125I]iodorotenone and 7′(Z)-[125I]iodorotenol

Mitochondrial avid radioprobes. Preparation and evaluation of 7′(Z)-[125I]iodorotenone and 7′(Z)-[125I]iodorotenol

Reverse Redistribution Phenomenon on Rest 99mTc-Tetrofosmin Myocardial Single Photon Emission Computed Tomography Involves Impaired Left Ventricular Contraction in Patients With Acute Myocardial Infarction

Changes of Thyroidal Tc-99m Tetrofosmin Uptake and Wash-Out in Patients with Hashimoto’s Thyroiditis

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