Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma

Purpose  Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC. Methods   ¹¹¹In-DOTA-(D)Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH₂ (¹¹¹In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands ^99mTc-N₄-Gly-(D)Glu-(Glu)₅-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH₂ (^99mTc-demogastrin 2) and ¹¹¹In-DOTA-(D)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH₂ (¹¹¹In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3–5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake. Results   ^99mTc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients. ¹¹¹In-DOTA-CCK and ¹¹¹In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides. Conclusion   ^99mTc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that ¹¹¹In-DOTA-CCK and ¹¹¹In-DOTA-MG11 have less potential as imaging agents than ^99mTc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

fMRI of optokinetic eye movements with and without a contribution of smooth pursuit.

BACKGROUND AND PURPOSE: Optokinetic eye movements are elicited when tracking a moving pattern. It can be argued that a moving pattern of stripes invokes both the optokinetic and the smooth pursuit eye movement system, which may confound the observed brain activation patterns using functional magnetic resonance imaging (fMRI). A moving pattern of limited-lifetime-dot stimulation does not target the smooth pursuit eye movement system. METHODS: fMRI was used to compare the cortical activity elicited by an optokinetic eye movement response evoked by a moving pattern of stripes and a moving pattern of limited lifetime dots. RESULTS: The eye movement behavior showed that both types of stimuli evoked an adequate and similar optokinetic eye movement response, but stimulation with stripes evoked more activation in the frontal and parietal eye fields, MT/V5, and in the cerebellar area VI than stimulation with limited-lifetime dots. CONCLUSIONS: These brain areas are implicated in smooth pursuit eye movements. Our results suggest that indeed both the optokinetic and the smooth pursuit eye movement system are involved in tracking a moving pattern of stripes.     

Urodynamic and electrophysiologic studies in evaluating congenital neurogenic bladder

We investigated 50 patients with a congenital neurogenic bladder secondary to myelomeningocele (38), sacral agenesis (5) and occult spinal dysraphism (7). There were 25 males and 25 females, aged from 1 month to 29 years (mean age at the time of evaluation was 9.2 years). Pressure-Flow-EMG study was obtained in every instance. In addition, 25 patients underwent electrophysiological testing (sacral reflex arc testing and somatosensory evoked potentials from the pudendal nerve). The patients were then classified according to the urodynamic and electrophysiological results. We allocated the patients into a "functional" classification as recommended by Van Gool. This classification is useful in the selection of proper therapy, and in the definition of the risks of upper tracts deterioration.