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[en] Coronary artery disease (CAD) is the leading cause of mortality in the Western world. Multiple parameters have been investigated to predict prognosis in CAD patients. The prognostic value of the left ventricular ejection fraction (LVEF) in patients with CAD is well established. More recently, left ventricular (LV) volumes have also shown prognostic value. Due to the favourable imaging characteristics of technetium-99m (high count density), the development of ^99mTc-labelled myocardial perfusion tracers has made it possible to perform an electrocardiogram-gated acquisition during routine myocardial perfusion imaging. This enables assessment of LVEF and LV volumes during myocardial perfusion scintigraphy. This review considers the possible prognostic abilities of LV volume assessment by gated cardiac SPET. (orig.)

[en] Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1±17.5 vs 63.2±14.9 mg 100 g^-1 min^-1, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28±0.35; controls, 1.55±0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81±17 ml 100 g^-1 min^-1; saline, 75±19 ml 100 g^-1 min^-1, P=NS) or MVR (deferoxamine, 1.0±0.5 mmHg ml^-1 100 g^-1 min^-1; saline, 1.2±0.6 mmHg ml^-1 100 g^-1 min^-1, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary microvasculature to sympathetic stimulation. Hydroxyl radicals may play a role in the pathogenesis of flow abnormalities in type 1 diabetes. (orig.)

[en] The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET α-emitter astatine-211 (²¹¹At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 (¹²³I), 340-fold for technetium-99m pertechnetate (^99mTcO₄^-) and 60-fold for ²¹¹At. Cellular ²¹¹At accumulation was found to be dependent on extracellular Na⁺ ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and ^99mTcO₄^- uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated ²¹¹At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and ²¹¹At were rapidly (apparent t_1/2 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times (¹²³I), 25 times (^99mTcO₄^-) and 10 times (²¹¹At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of ¹²³I and ²¹¹At, respectively, was found in NIS tumours by region of interest analysis (n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for ¹²³I, 5.2 h for ²¹¹At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq_tumour for ¹³¹I and 50.3 Gy/MBq_tumour for ²¹¹At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy α-emitter ²¹¹At is efficiently transported by NIS. Application of ²¹¹At may direct higher radiation doses to experimental tumours than those calculated for ¹³¹I. Thus, ²¹¹At may represent a promising alternative radionuclide for future NIS-based tumour therapy. (orig.)

[en] The purpose of this prospective study was to evaluate yttrium-90 glass microsphere treatment of unresectable liver metastases by fluorine-18 fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET), and to compare the effectiveness of [¹⁸F]FDG PET for this purpose with that of computed tomography (CT) or magnetic resonance imaging (MRI) and determination of the serum carcinoembryonic antigen (CEA) level. Thirteen hepatic lobes from eight consecutive patients with colorectal cancer referred for ⁹⁰Y-glass microsphere treatment of unresectable liver metastases who underwent both baseline (pretreatment) and 3-month posttreatment PET were studied. All patients also had correlative pre- and posttreatment CT or MRI for evaluation of the anatomic response and serum CEA determination for assessment of the total tumor load, as well as pretreatment hepatic intra-arterial technetium-99m macroaggregated albumin scan for lung shunting evaluation and hepatic arteriography for assessment of vascular anatomy and treatment. ⁹⁰Y-glass microspheres were infused via an intra-arterial catheter under low pressure. Dedicated whole-body PET scans were analyzed visually and compared by lesion and by lobe with CT or MRI. A metabolic response after ⁹⁰Y treatment to single or both hepatic lobes, assessed by PET, was present in a significantly higher proportion of the lobes than was an anatomic response, evaluated by CT or MRI (12 vs 2 lobes respectively, P<0.0002). Posttreatment PET showed no, stable, progressive, and new extrahepatic metastases in two, three, one, and two patients respectively. Following treatment, serum CEA decreased significantly, correlating with PET but not with CT or MRI. Thus, the study demonstrated a significant difference between the metabolic and the anatomic response after ⁹⁰Y-glass microsphere treatment for unresectable liver metastases in colorectal cancer. PET appears to be an accurate indicator of treatment response. (orig.)