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Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct.

UNLABELLED: Technetium-99m-pyrophosphate (PYP) is bound to calcium in necrotic myocardium and has been used clinically to evaluate myocardial infarction. Technetium-99m-PYP is also reported to accumulate in myocardium with unstable angina pectoris and it is speculated that severe ischemia with noninfarcted tissue may also increase uptake of 99mTc-PYP. In this paper, 99mTc-PYP uptake was determined in various models of myocardial ischemia of short duration to examine its applicability to the assessment of myocardial viability. METHODS: In 23 open-chest dogs under anesthesia, models of ischemia-reperfusion of the left anterior descending artery (LAD) subjected to ischemia for 10, 30 or 60 min were produced. Wall motion was examined by echocardiography and myocardial blood flow was calculated using colored microspheres. Technetium-99m-PYP was injected after each ischemic intervention and reperfusion. RESULTS: Technetium-99m-PYP showed 1.18 +/- 0.009 in the uptake ratio (ischemic area/normal area) following 10-min ischemia (11 dogs). The uptake ratio following 30-min ischemia (8 dogs) showed a significantly higher increase than that following 10-min ischemia (4.09 +/- 1.75; p < 0.05), permitting in vivo and ex vivo imaging. After 60-min ischemia resulting in infarction (4 dogs), 99mTc-PYP uptake of the ischemic area showed an uptake ten times that of the normal area (transmural: 12.2 +/- 2.9, epicardium: 7.5 +/- 1.9, endocardium: 16.8 +/- 4.1). CONCLUSIONS: These findings indicate that since 99mTc-PYP accumulates in injured myocardium, its concurrent use with blood flow imaging is useful for the assessment of severity of ischemia, injured area and myocardial viability.

Animals↗

Value of technetium 99m sestamibi iodine 123 imaging in reoperative parathyroid surgery.

BACKGROUND: The purpose of this study was to assess the contribution of technetium 99m sestamibi iodine 123 (T/S) imaging to preoperative and intraoperative management of patients with persistent hyperparathyroidism. METHODS: During a period of 10 months, all patients being prepared for reoperative parathyroid surgery (n = 10), two patients deemed significant operative risks (one patient with severe chronic obstructive pulmonary disease and one patient with severe cervical spine ankylosing spondylitis), and two patients who had undergone prior thyroid operation were studied with T/S imaging. Six patients undergoing reoperative surgery had undergone one, three had undergone two, and one had undergone three prior procedures. RESULTS: T/S imaging correctly localized 14 of 16 parathyroid tumors. By comparison, only 1 of 6 thallium technetium and 3 of 12 computed tomography (CT) scans (in seven patients) were positive. T/S imaging guided the reoperative surgical approach accurately in 12 of 14 patients, including one case of an undescended left lower gland at the level of the mandible and identification of a third gland on the left in another case. Sternal split was required to remove three lesions localized by T/S imaging, two beneath the aortic arch and one nestled in the aortopulmonary window in a patient who had undergone two prior procedures including a sternal split. In these three cases T/S imaging was particularly useful, because CT scans, thallium technetium scans, magnetic resonance imaging, and arteriography were not diagnostic. The outcome after operation was favorable in all 14 cases, with correction of hypercalcemia and no permanent laryngeal nerve injuries or hypocalcemia. CONCLUSIONS: We concluded that T/S imaging is more accurate than thallium technetium and CT scans in evaluation of patients with persistent hyperparathyroidism.

Adult↗

["Reverse reperfusion" in myocardial scintigraphy perfusion with technetium-99m isonitrile. Incidence and clinical implications].

PURPOSE: Evaluation of the incidence and clinical implications of perfusion defects that appear worse in the rest than the stress myocardial perfusion imaging with technetium-99m isonitrile (MIBI), similar to the reverse redistribution described with thallium-201. METHODS: The studies of 730 consecutive patients with known or suspected coronary artery disease who underwent either diagnostic or prognostic (after myocardial infarction) technetium-99mMIBI planar scans were reviewed. Usual planar images were subjective and semi-quantitative analyzed. Patients were divided in two groups according to the indication of the test. The incidence of the reverse reperfusion pattern, the correlative findings with the angiographic coronary anatomy, when available, and its clinical implications were assessed. RESULTS: Three in the 540 (0.55%) patients of the diagnostic group and 6 out of the 190 (3.15%) patients of the myocardial infarction group have shown the "reverse reperfusion" pattern, with an overall incidence of 1.23%. Perfusion defects were anterior in 2 and inferior in 1 patient of the diagnostic group, compared to 4 anterior and 2 inferior within the prognostic population patients. One patient of the diagnostic group and 4 of the prognostic group showed ST-T changes on the exercise ECG. All of them achieved at least 85% of the maximum predicted heart rate during the stress test. The only patient with the "reverse reperfusion" pattern in the diagnostic group had no coronary disease at angiography, while the 6 patients in the post myocardial infarction group have shown either an occluded (2 cases) or recanalized infarct related artery (2 cases) and remote coronary disease (2 cases). Three of them underwent successful coronary angioplasty based on clinical and laboratory evidences of ischemia. CONCLUSION: The "reverse reperfusion" with technetium 99-m MIBI is an uncommon finding and may be associated with jeopardized myocardium after infarction, although its predictive value for recanalized infarct related artery seems to be very low. It seems to provide no added value towards coronary artery disease diagnosis. Additional experience is required in selected subgroups of patients in order to clarify the clinical value of the "reverse reperfusion" pattern with the technetium-99m MIBI.

Adult↗

Technetium-99m-sestamibi scanning in recurrent medullary thyroid carcinoma.

UNLABELLED: The presence of recurrent medullary thyroid carcinoma (MTC) can be detected early by measurement of serum calcitonin levels, but the localization of recurrent tumors is often difficult. METHODS: We compared 99mTc-sestamibi scans with computed tomographic (CT) scans in 10 patients with recurrent MTC, who had basal serum calcitonin values ranging from 220-61800 ng/liter. Two patients additionally had bone scans performed because of the clinical suspicion of bone metastases. RESULTS: Seven of the 10 patients had at least one site of abnormal 99mTc-sestamibi uptake, and all of these patients had basal serum calcitonin values > 6000 ng/liter. Only five of the 10 patients had abnormal CT scans. Technetium-99m-sestamibi scans detected 22 abnormal sites in the soft tissues of the neck and chest, while CT scans detected only 11 lesions in the neck and chest. Five of these sestamibi positive sites (in the neck and mediastinum of one patient) were confirmed histologically to represent MTC. When imaging the liver, CT scans detected 47 lesions in three patients while 99mTc-sestamibi scans detected none. One of these liver lesions was confirmed as MTC histologically. When imaging bone in two of the patients, the bone scans detected 17 abnormal sites, while 99mTc-sestamibi scans detected six abnormal sites. CONCLUSION: Technetium-99m-sestamibi scans complement CT and bone scans in the localization of recurrent MTC in patients with extremely high calcitonin levels. Technetium-99m-sestamibi scans are more sensitive than CT scans in the assessment of the soft tissues of the neck and chest, but CT is more appropriate for imaging hepatic lesions and bone scans are better for imaging bone lesions. Technetium-99m-sestamibi scans are unlikely to be abnormal in patients with only mild elevation of calcitonin.

Adult↗

Involvement of glutathione in loss of technetium-99m-MIBI accumulation related to membrane MDR protein expression in tumor cells.

UNLABELLED: It was reported recently that 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) uptake is drastically reduced in cancer cells that express the multidrug resistance (MDR) product, Pgp 170 kDa (Pgp), suggesting that 99mTc-MIBI is a transport substrate for this transmembrane glycoprotein. In our study, we explored if another pump, a multidrug resistance-associated protein (MRP), could affect 99mTc-MIBI uptake. In addition, we studied the involvement of intracellular glutathione (GSH) as a modulator of 99mTc-MIBI uptake by both Pgp and MRP proteins. METHODS: MDR1 and MRP gene expression in seven human tumor cell lines was determined on a transcriptional level by reverse transcriptase polymerase chain reaction and on a protein level using immunocytochemistry. Technetium-99m-MIBI uptake was quantified by measuring radioactivity retained in the cells incubated at 37 degrees C in the presence or absence of buthionine sulfoximine (BSO), which depletes cellular GSH. The cellular GSH content was determined with Ellman's reagent. RESULTS: Cell lines were classified according to their phenotypic characteristics: 1/MRP-/Pgp-: breast cancer cells (MCF7), lung carcinoma cells (H69S) and mouth epidermoid tumor cells (KB 3.1), 2/MRP-/Pgp+: MCF7 mdr+, KBA.1; and 3/MRP+/Pgp-: small-cell lung carcinoma (H69 AR and A 549). Technetium-99m-MIBI uptake was significantly lower in cells expressing MRP as well as Pgp compared to MRP/Pgp cells. Depletion of GSH by BSO resulted in an increase of 99mTc-MIBI uptake in multidrug resistant cells overexpressing MRP but not expressing Pgp. CONCLUSION: Technetium-99m-MIBI is extruded by both Pgp and MRP efflux pumps. However, MRP action is indirect and involves intracellular GSH for a presumed interaction with the 99mTc-MIBI before its effLux. Technetium-99m-MIBI seems to be a good candidate for a noninvasive marker to diagnose MDR1 related to Pgp and MRP expression in tumors of different origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length.

UNLABELLED: The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.

Animals↗

Blood-pool imaging using technetium-99m-labeled liposomes.

UNLABELLED: This study evaluated two 99mTc-liposome formulations as potential blood-pool agents in comparison with standard 99mTc-red cells and 99mTc-human serum albumin (HSA). METHODS: Liposomes with no surface modification or coated with polyethylene glycol (PEG) were labeled with 99mTc using the lipophilic chelator, HMPAO. Autologous red cells were labeled with 99mTc using in vitro or in vivo techniques. Technetium-99m-HSA was supplied commercially. Rabbits were injected intravenously with 99mTc-liposomes, 99mTc-red cells or 99mTc-HSA. Static images were acquired and blood samples collected. RESULTS: Technetium-99m-liposome images showed prominent blood-pool activity compared to lung and liver activities, which were similar to those acquired for 99mTc-red cells, but better than 99mTc-HSA. Heart-to-lung ratios were not significantly different between 99mTc-liposome formulations or for either formulation compared to 99mTc-red cells. The ratios were higher, however, than for 99mTc-HSA. Heart-to-liver ratios were higher for PEG 99mTc-liposomes than they were for neutral 99mTc-liposomes and 99mTc-HSA, but were not significantly different than 99mTc-red cells. Bladder activities for both 99mTc-liposome formulations were 3-6 times lower than for the other agents. PEG 99mTc-liposomes remained in circulation 1.6 times longer than any of the other agents. CONCLUSIONS: Technetium-99m-liposomes, independent of surface modification, had excellent circulation persistence and in vivo stability when compared to 99mTc-red cells and 99mTc-HSA. PEG 99mTc-liposomes performed better than neutral 99mTc-liposomes due to lower liver background activity. Advantages of PEG 99mTc-liposomes compared to 99mTc-red cells include: (a) only one venipuncture, (b) little exposure to patient's blood, (c) excellent in vitro and in vivo stability and (d) lack of drug interference.

Animals↗

Technetium-99m tetrofosmin uptake in lung cancer: comparison with thallium-201.

Technetium-99m tetrofosmin and thallium-201 lung SPECT imaging were performed in a patient with adenocarcinoma of the lung. Significant activities in the lung lesion were clearly depicted on both technetium-99m tetrofosmin and thallium-201 SPECT imaging. The early uptake, delayed uptake ratios and retention indices of the tumor were 2.75, 2.39 and -1.31 for thallium-201 imaging and 3.09, 2.27 and -26.5 for technetium-99m tetrofosmin imaging, respectively. This preliminary report suggests that technetium-99m tetrofosmin may have potential as a tumor imaging agent.

Adenocarcinoma↗

Tomographic myocardial perfusion imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia: correlation with thallium-201 imaging.

Single-photon emission computed tomographic imaging with technetium-99m teboroxime during exercise has been found to be feasible and the results correlate with those obtained with thallium-201. This study examined the feasibility of this technique and compared tomographic imaging with technetium-99m teboroxime during adenosine-induced coronary hyperemia with thallium-201 imaging. With the patient positioned on the imaging table, adenosine was infused at a rate of 140 micrograms/kg per min for 6 min. At 4 min, 20 to 25 mCi (740 to 925 MBq) of technetium-99m teboroxime was injected intravenously and imaging was started as soon as the infusion was completed with use of a 180 degrees anterior arc and 32 stops at 10 s/stop (total imaging time 7.8 min). Rest images were obtained 60 to 90 min later with use of a similar dose of technetium-99m teboroxime. Exercise tomographic thallium images were obtained within 2 weeks of the teboroxime studies. In the 20 patients studied, the teboroxime images were normal in 2 (50%) of 4 normal subjects and abnormal in 15 (94%) of 16 patients with coronary artery disease; 4 of the 15 had a fixed defect and 11 a reversible defect. There was agreement between teboroxime and thallium studies in 16 patients (80%), in 319 (80%) of 400 segments and in 50 (83%) of 60 vascular segments (p less than 0.05). In two normal subjects, an apparent fixed defect involving the inferior wall was seen on the teboroxime but not the thallium images and was thought to be due to an attenuation artifact secondary to extracardiac activity in the left lobe of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Intrahepatic, extramedullary hematopoiesis mimicking hemangioma on technetium-99m red blood cell SPECT examination.

Cavernous hemangiomas are the most common lesion of the liver. Because of the risk of hemorrhage inherent in percutaneous biopsy of such lesions, noninterventional modalities (such as CT, ultrasound, MRI and Technetium-99m red blood cell imaging) have been utilized for differentiating them from other lesions. The sensitivities and specificities of these techniques vary greatly. Technetium-99m red blood cell imaging with planar and SPECT imaging has been shown to have an overall sensitivity of 89%, a specificity of 100%, and an overall accuracy of 92%. Despite its high accuracy, rare false positives have been reported with Technetium-99m red blood cell imaging with SPECT. Review of the literature indicates four cases of hepatocellular carcinoma, one case of hepatic angiosarcoma, and one case of hepatic metastases from colorectal carcinoma as having an appearance identical to hemangioma with this modality. We present an additional false positive of a focal region of intrahepatic extramedullary hematopoiesis in a patient with Gaucher's disease as having an appearance on Technetium-99m red blood cell imaging with SPECT identical to that of hemangioma.

Animals↗

Clinical experience with technetium 99m teboroxime.

Technetium 99m teboroxime is a boronic acid adduct of technetium dioxime complex, a neutral lipophilic technetium-containing myocardial perfusion imaging agent with high myocardial extraction, rapid myocardial washout, and entero-hepatic excretion. Early "redistribution" occurs, and, based on preliminary animal data, appears to be due to differential washout alone since there is no reuptake of teboroxime into the heart; however, for practical purposes two injections of tracer, at stress and at rest, are used clinically. Due to the high photon flux of technetium, diagnostic images can be acquired in the narrow time window between the end of blood clearance and peak hepatic uptake. To begin an acquisition within 2 minutes of tracer injection, the patient must be moved rapidly from the treadmill to a camera that is set and ready to count. A complete set of planar images can be completed in less than 5 minutes. Optimal single photon emission computed tomography (SPECT) imaging requires a continuously counting single detector camera or a three-headed camera to complete acquisition in less than 10 minutes. The image quality is comparable to thallium 201 and the imaging time is a fraction of the time required to complete SPECT thallium scans. Both left ventricular function (ejection fraction) and planar imaging can be performed in less than 4 minutes, without moving the patient from the treadmill, using the Sim-400 (Scinticor, Milwaukee, WI), a portable high count-rate, multicrystal scintillation camera. Because teboroxime maintains high myocardial extraction at high myocardial flow, it may be uniquely suited to be used in combination with pharmacological stress, which does not require patient movement between stress and imaging. Work is in progress to further refine and optimize imaging protocols using teboroxime.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Technetium-99m-labeled receptor-specific small-molecule radiopharmaceuticals: recent developments and encouraging results.

The development of technetium-99m-labeled small-molecule radiopharmaceuticals directed at specific high-affinity binding sites, as are found in receptors for hormones and neurotransmitters, transport systems, and certain enzymes, is a natural outgrowth from the successful development of technetium radiopharmaceuticals for imaging flow and metabolism. Although many receptor-specific radiopharmaceuticals labeled with PET and other SPECT isotopes already exist, the low cost and widespread availability of technetium-99m would make their 99mTc-labeled counterparts much more accessible to the medical community. This review has four goals: (a) To survey and analyze critically the results of a flurry of research activity in this area in recent years, which has led to the preparation of a number of novel technetium-labeled radiopharmaceuticals targeted at high-affinity sites, a few of which appear to be very promising; (b) to provide a conceptual analysis of how these agents are being designed; (c) to provide a context in terms of binding and uptake behavior by which these agents should be judged; and (d) to highlight emerging knowledge on the structure of receptors and related high-affinity binding biomolecules and their distribution, which may serve as reference points for understanding the results that have been obtained so far, and may be useful guides for future design.

Animals↗

Rhenium(V) and technetium(V) complexes with phosphoraneimine and phosphoraneiminato ligands.

Air-stable rhenium(V) nitrido complexes are formed when [ReOCl3(PPh3)2], [NBu4][ReOCl4], or [NBu4][ReNCl4] are treated with an excess of silylated phosphoraneiminates of the composition Me3SiNPPh3 or Ph2P(NSiMe3)CH2PPh2 in CH2Cl2. Complexes of the compositions [ReNCl(Ph2PCH2PPh2NH)2]Cl (1), [ReN(OSiMe3)(Ph2PCH2PPh2NH)2]Cl (2) or [ReNCl2(PPh3)2] (3) were isolated and structurally characterized. The latter compound was also produced during a reaction of the rhenium(III) precursor [ReCl3(PPh3)2(CH3CN)] and Me3SiNPPh3. Nitrogen transfer from the phosphorus to the rhenium atoms and the formation of nitrido ligands were observed in all examples. All products of reactions with an excess of the potentially chelating phosphoraneiminate Me3SiNP(Ph2)CH2PPh2 contain neutral Ph2PCH2PPh2NH ligands. The required protons are supplied by a metal-induced decomposition of the solvent dichloromethane. The Re-N(imine) bond lengths (2.055-2.110 A) indicate single bonds, whereas the N-P bond with lengths between 1.596 A and 1.611 A reflect considerable double bond character. An oxorhenium(V) phosphoraneiminato complex, the dimeric compound [ReOCl2(mu-N-Ph2PCH2PPh2N)]2 (4), is formed during the reaction of [NBu4][ReOCl4] with an equivalent amount of Ph2P(NSiMe3)CH2PPh in dry acetonitrile. The blue neutral complex with two bridging phosphoraneiminato units is stable as a solid and in dry solvents. It decomposes in solution, when traces of water are present. The rhenium-nitrogen distances of 2.028(3) and 2.082(3) A are in the typical range of bridging phosphoraneiminates and an almost symmetric bonding mode. Technetium complexes with phosphoraneimine ligands were isolated from reactions of [NBu4][TcOCl4] with Me3SiNPPh3, and [NBu4][TcNCl4] with Me3SiNP(Ph2)CH2PPh2. Nitrogen transfer and the formation of a five-coordinate nitrido species, [TcNCl2(HNPPh3)2] (5), was observed in the case of the oxo precursor, whereas reduction of the technetium(VI) starting material and the formation of the neutral technetium(V) complex [TcNCl2(Ph2PCH2PPh2NH)] (6) or [TcNCl(Ph2PCH2PPh2NH)2]Cl (7) was observed in the latter case. Both technetium complexes are air stable and X-ray structure determinations show bonding modes of the phosphoraneimines similar to those in the rhenium complexes.

Journal Article↗

TcO(PnA.O-1-(2-nitroimidazole)) [BMS-181321], a new technetium-containing nitroimidazole complex for imaging hypoxia: synthesis, characterization, and xanthine oxidase-catalyzed reduction.

A technetium(V)oxo nitroimidazole complex that shows promise for imaging regional hypoxia in vivo, [BMS-181321, TcO(PnAO-1-(2-nitroimidazole))] (1) was prepared from 3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane -2,10-dione dioxime, a 2-nitroimidazole-containing derivative of propyleneamine oxime (PnAO). The 99Tc complex [99Tc]Oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8- diazaundecane-2,10-dione dioximato]-(3-)-N,N',N'',N''']technetium (V) was synthesized both from pertechnetate and [TcO(Eg)2]- (Eg = ethylene glycol). A new synthetic route to TcO(PnAO) (2) is also described. 99TcO(PnAO-1-(2-nitroimidazole)) was characterized by 1H NMR, IR, and UV/vis spectroscopy, HPLC, FAB mass spectrometry, and X-ray crystallography. Electrochemistry of 1 reveals that the nitro redox chemistry found in the ligand is maintained upon coordination to technetium but shifts to a slightly more positive potential. Using chiral HPLC (Chiracel OD), 99mTc (1) was resolved into its two enantiomers. However, the two isomers were found to racemize quickly (t1/2 < 2 min) in the presence of water. Localization of 1 is believed to be mediated by enzymatically catalyzed reduction of the nitroimidazole group, so the in vitro reaction of 99Tc(1) with the nitroreductase enzyme xanthine oxidase (XOD) was studied. XOD catalyzed the quantitative reduction of the nitroimidazole group on the molecule under anaerobic conditions in the presence of hypoxanthine. No reaction was noted using a non-nitro-containing complex (2). The rate of reduction of the Tc-nitroimidazole complex (1.5 +/- 0.16 nmol/min per unit XOD) was faster than that observed previously for the nitroimidazole BATOs (BATO = boronic acid adduct of technetium dioxime) and was about two-thirds that of fluoromisonidazole, a compound that has proven useful for imaging hypoxia in humans when labeled with 18F. These data suggest that BMS-181321 (1) has the potential to be recognized by nitroreductase enzymes in vivo, thus satisfying one of the criteria required for this potential hypoxia imaging agent.

Chromatography, High Pressure Liquid↗

Homodimeric and heterodimeric bis(amino thiol) oxometal complexes with rhenium(V) and technetium(V). Control of heterodimeric complex formation and an approach to metal complexes that mimic steroid hormones.

We have investigated the possibility of preparing complexes of rhenium and technetium whose shape resembles that of ligands for steroid receptors. The general structure of N2S2 complexes of oxorhenium(V) and oxotechnetium(V) is such that they could replace the BC ring system of steroid, thereby generating a metal complex system with considerable size and shape similarity to a steroid. Such a metal-integrated steroid-shaped complex can be constructed as a heterodimer of two different amino thiols; complexes of rhenium and technetium with such heterodimeric bis-bidentate structure have not been systematically studied. In this investigation, we have shown that complexes of this nature form readily when appropriate metal precursors are combined with a mixture of amino thiols. In the systems we have studied, heterodimeric complex formation is preferred over homodimeric complex formation, and in one system where we were able to obtain an X-ray crystal structure, this oxorhenium heterodimer had the desired trans geometry. These rhenium and technetium-99m complexes are reasonably stable toward ligand exchange; they can be readily purified by chromatography under appropriate conditions, and the one technetium-99m complex studied in vivo shows some persistence in blood and gives good initial uptake in several tissues. The convenient and selective formation of such bis-bidentate heterodimeric complexes suggests that the development of metal-integrated complexes that resemble ligands for receptors may be possible.

Animals↗

Technetium-99m tetrofosmin single photon emission computed tomography in the evaluation of suspected lung cancer.

Technetium-99m-tetrofosmin is a radiopharmaceutical employed for myocardial imaging, which has recently emerged as useful in the visualization of tumors. In this study technetium-99m-tetrofosmin was evaluated for its accuracy in differentiating malignant from benign pulmonary lesions, and in detecting mediastinal node metastasis due to lung cancer. Eighty-one patients with a solitary lung lesion on the chest radiograph and/or CT scan were submitted to chest single photon emission computed tomography after technetium-99m-tetrofosmin injection (740 MBq i.v.). The scintigraphic findings were correlated to the final histopathological diagnosis, demonstrating abnormal tracer accumulation in 51 of 54 malignant lesions (sensitivity 94%) and in 4 out of 27 benign conditions (specificity 85%), yielding an accuracy of 91%. Mediastinal lymph-node involvement was evaluated in 35 patients with non small cell lung cancer who underwent mediastinoscopy and/or surgery. Tetrofosmin accuracy (89%) was significantly higher than that of CT (69%, p < 0.05); the false negative scintigraphic results were in nodes sized less than 1 cm. In conclusion, technetium-99m-tetrofosmin imaging is useful in distinguishing malignant from benign pulmonary lesions, and in non-invasively assessing mediastinal node metastases from non small cell lung cancer, especially in patients with enlarged nodes by CT scan.

Adult↗

Technetium-pertechnetate uptake by ectopic antral mucosa. An experimental study.

The ability of ectopically placed fundic mucosa and retained antral mucosa to concentrate technetium has previously been demonstrated. The ability of ectopically placed antral mucosa to concentrate technetium was investigated. The denervated antrum implanted into the colon concentrated technetium in 5 dogs. However, this response was significantly less than that of parietal cell-containing mucosa (P less than 0.005) of the stomach. Technetium scanning may be useful in detecting ectopic and retained antral mucosa.

Animals↗

Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of myocardial redistribution.

UNLABELLED: Technetium-99m-N-NOET is a new 99mTc-labeled, neutral cardiac perfusion imaging agent which has been shown to undergo apparent redistribution in animal models and in humans. The purpose of this study was to investigate the interaction of 99mTcN-NOET with red blood cells (RBCs) and to determine the effects of these interactions on myocardial uptake and clearance of 99mTcN-NOET. METHODS: After bolus administration, myocardial 99mTcN-NOET clearance was monitored for 1 hr using a sodium iodide detector in 22 isolated, buffer-perfused rat hearts. Hearts were perfused as follows: seven controls with Krebs-Henseleit (KH) buffer (Group 1), five hearts with KH containing RBCs (Group 2), five hearts with KH containing RBCs and albumin (Group 3), five hearts with KH containing RBCs and dextran (Group 4). In a separate protocol, RBCs were incubated in 99mTcN-NOET and then perfused through five hearts (Group 5). RESULTS: Technetium-99m-N-NOET myocardial uptake (%ID) was significantly lower in all RBC groups (RBCs = 5.0% +/- 1.7%; RBCs + albumin = 8.2% +/- 2.1%; RBCs + dextran = 4.0% +/- 0.8%; incubated RBCs = 8.8% +/- 1.5%) compared with controls (72.2% +/- 2.8%; p < 0.05). Retention (99.4% +/- 0.6%) was near linear in the KH control group with virtually no fractional clearance at 60 min. Retention in groups whose perfusates contained RBCs (RBCs = 62.2 +/- 4.2%; RBCs + albumin = 29.9 +/- 4.3%; RBCs + dextran = 69.3 +/- 3.6%) were all significantly lower than control. Addition of albumin to RBC perfusate resulted in significantly lower retention (29.9% +/- 4.3%; p < 0.01) than was observed in RBC perfusate alone (62.2% +/- 4.2%). Substitution of dextran for albumin produced retention similar to RBCs alone (69.3% +/- 3.6%; p = ns). In a separate protocol, RBC binding of 99mTcN-NOET was high (64.4% +/- 8.6%) in triple-washed RBCs. Technetium-99m-N-NOET bound to RBCs was subsequently extracted from red cells by the myocardium when those cells were infused into hearts. CONCLUSION: Technetium-99m-N-NOET has high binding affinity to blood elements and transfers bidirectionally between myocardium and blood. The interaction of 99mTcN-NOET with blood elements represents a potential mechanism of redistribution.

Animals↗