In vivo preclinical evaluation of the new 68Ga-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography.

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays an important role in tumor development and formation of metastases. It was earlier reported that cyclodextrin derivatives have a high affinity to form complexes with PGE2. Based on these results radiolabeled cyclodextrins - as new radiopharmaceuticals - may open a new pathway in the in vivo imaging and diagnosis of PGE2 positive tumors. The aims of this study were to synthetize the PGE2 specific 68Ga-labeled NODAGA-randomly methylated beta-cyclodextrin (68Ga-NODAGA-RAMEB) and investigate its tumor-targeting properties. NODAGA-RAMEB was labeled with Gallium-68 (68Ga), and the radiochemical purity (RCP%), partition coefficient (logP values), and in vitro-in vivo stability of 68Ga-NODAGA-RAMEB were determined. After intravenous injection of 68Ga-NODAGA-RAMEB the accumulation in organs and tissues was monitored in vivo by positron emission tomography (PET) and ex vivo by gamma counter in BxPC-3 and PancTu-1 tumor-bearing CB17 SCID mice. The RCP% of the newly synthesized 68Ga-NODAGA-RAMEB was higher than 98%. The molar activity was 15.34 ± 1.93 GBq/µmol. The logP of 68Ga labeled NODAGA-RAMEB was - 3.63 ± 0.04. Biodistribution studies showed high accumulation of 68Ga-NODAGA-RAMEB in PGE2 positive BxPC-3 tumors; approximately 15-20-fold higher radiotracer uptake was observed, than that of the background. 68Ga-labeled RAMEB is a promising radiotracer in PET diagnostics of PGE2 positive tumors.

The Effect of Passive Movement for Paretic Ankle-Foot and Brain Activity in Post-Stroke Patients.

BACKGROUND: This study aims at investigating the short-term efficacy of the continuous passive motion (CPM) device developed for the therapy of ankle-foot paresis and to investigate by fMRI the blood oxygen level-dependent responses (BOLD) during ankle passive movement (PM). METHODS: Sixty-four stroke patients were investigated. Patients were assigned into 2 groups: 49 patients received both 15 min manual and 30 min device therapy (M + D), while the other group (n = 15) received only 15 min manual therapy (M). A third group of stroke patients (n = 12) was investigated by fMRI before and immediately after 30 min CPM device therapy. There was no direct relation between the fMRI group and the other 2 groups. All subjects were assessed using the Modified Ashworth Scale (MAS) and a goniometer. RESULTS: Mean MAS decreased, the ankle's mean plantar flexion and dorsiflexion passive range of motion (PROM) increased and the equinovalgus improved significantly in the M + D group. In the fMRI group, the PM of the paretic ankle increased BOLD responses; this was observed in the contralateral pre- and postcentral gyrus, superior temporal gyrus, central opercular cortex, and in the ipsilateral postcentral gyrus, frontal operculum cortex and cerebellum. CONCLUSION: Manual therapy with CPM device therapy improved the ankle PROM, equinovalgus and severity of spasticity. The ankle PM increased ipsi- and contralateral cortical activation.

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

OBJECTIVE: Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. METHOD: Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. RESULTS AND DISCUSSION: Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. CONCLUSIONS: The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.