Assessment of the 18F-labeled PET tracer LMI1195 for imaging norepinephrine handling in rat hearts.

UNLABELLED: A novel (18)F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of (18)F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. METHODS: Tracer accumulation in the heart was studied over time after intravenous administration of (18)F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). RESULTS: (18)F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the (18)F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved (18)F-LMI1195 uptake after desipramine pretreatment. CONCLUSION: In rats, cardiac uptake of (18)F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting (18)F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

Scintigraphic evaluation of jejunal interposition after distal esophageal resection for early Barrett's carcinoma.

Subtotal esophagectomy still is the major treatment for early Barrett's carcinoma. The inevitable loss of the gastric reservoir leaves an unresolved functional problem. Distal esophageal resection combined with a short jejunal interposition might be a safe alternative with the advantage of better functional results. In this series, 12 or more months after limited surgery for early Barrett's carcinoma 8 patients underwent functional investigation by alimentary scintigraphy. The activity of a technetium-labeled bolus passing through the esophagus and the jejunal interposition into the stomach was consecutively measured. Compared to 11 healthy controls the transit through the tubular esophagus showed no significant delay; transit time, however, increased with a bolus-induced dilation of the jejunal interposition. The length of the transit time through the jejunal interposition correlated with the length of the jejunal segment. The delay of bolus passage into the stomach did not result in substantial symptoms in jejunal segments shorter than 12 cm. Propulsive activity within the jejunal interposition resulted in a bolus transport into the stomach without any reflux to the esophagus. These data demonstrate good transport function and reflux prevention of short jejunal segments interposed between the esophagus and the stomach.

Cardiac phantom measurement validating the methodology for a cardiac multi-centre trial with positron emission tomography.

In an ongoing international multi-centre trial, positron emission tomography (PET) is being used to evaluate the effect of a new P-selectin antagonist on the infarct size in patients with acute myocardial infarction, treated with thrombolysis. Although it is possible to correct for site-dependent factors, it is desirable to reduce these factors to a minimum. Therefore, acquisition and reconstruction protocols have been defined that can be closely followed by all participating centres. The resulting reconstructed images are transferred to the core centre for central processing with semi-automatic software. This paper reports on the multi-centre phantom experiment that was carried out to assess the inter-centre reproducibility of defect size determination with this protocol. Also, the spatial resolution of the short axis slices was examined. In addition, the analysis procedure was applied to normal PET studies to evaluate the specificity of perfusion defect detection. The transmural cold defect in the phantom occupied 14.8% of the left ventricular area. The automated analysis was applied to the phantom measurements from the 14 participating PET cameras. It yielded an accurate estimate of 15.1% with a standard deviation of 0.6%, indicating excellent reproducibility. The spatial resolution in the short axis slices was similar for all PET systems: 9.6+/-0.8 mm. The same procedure produced a defect size of zero in the studies of normal volunteers. This study indicates that cardiac studies from multiple PET systems can be pooled for statistical analysis.