Preliminary assessment of extrastriatal dopamine D-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, 18F-fallypride.

We have identified the value of 18F-fallypride [(S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide], as a dopamine D-2 receptor radiotracer for the study of striatal and extrastriatal receptors. Fallypride exhibits high affinities for D-2 and D-3 subtypes and low affinity for D-4 (3H-spiperone IC50s: D-2 = 0.05 nM [rat striata], D-3 = 0.30 nM [SF9 cell lines, rat recombinant], and D-4 = 240 nM [CHO cell lines, human recombinant]). Biodistribution in the rat brain showed localization of 18F-fallypride in striata and extrastriatal regions such as the frontal cortex, parietal cortex, amygdala, hippocampus, thalamus, and hypothalamus. In vitro autoradiographic studies in sagittal slices of the rat brain showed localization of 18F-fallypride in striatal and several extrastriatal regions, including the medulla. Positron emission tomography (PET) experiments with 18F-fallypride in male rhesus monkeys were carried out in a PET VI scanner. In several PET experiments, apart from the specific binding seen in the striatum, specific binding of 18F-fallypride was also identified in extracellular regions (in a lower brain slice, possibly the thalamus). Specific binding in the extrastriata was, however, significantly lower compared with that observed in the striata of the monkeys (extrastriata/cerebellum = 2, striata/cerebellum = 10). Postmortem analysis of the monkey brain revealed significant 18F-fallypride binding in the striata, whereas binding was also observed in extrastriatal regions such as the thalamus, cortical areas, and brain stem.

Radiation safety considerations for PET centers.

This article explains why technologists handling positron-emitting radionuclides may have higher measured radiation exposures than technologists working with single-photon emitting radionuclides. We will summarize measurements we have made, as well as those reported by other authors. In addition, we will describe the procedures implemented to minimize exposure.

A miniature gamma camera.

We have described a mobile miniature-gamma-camera system for use in electrical trauma units and have presented images and imaging characteristics of a prototype system. The system has as its principal component a miniature gamma camera based on a PSPMT. The camera is 92 mm x 92 mm x 190 mm in size, weighs 5 kg, has a 48 mm x 48 mm field of view, and has an intrinsic resolution of approximately 3 mm FWHM and 6 mm FWTM. It is expected that devices of this type will be useful as imaging tools in electrical trauma units and laboratories where imaging studies regarding uptake mechanisms of radiopharmaceuticals for assessing tissue viability are carried out.

Laser alignment system for high-quality portable radiography.

In portable radiography, image quality is degraded by scattered radiation. Use of an accurately aligned, antiscatter grid can provide consistently high image quality, but the necessary precision for grid alignment is difficult to achieve with conventional techniques. The authors developed a simple laser alignment method for bedside radiography. A compact laser device is mounted on the collimator housing of a mobile radiography machine, so that the laser beam is precisely parallel to the central x-ray beam. A small reflector device, which attaches to the edge of the grid cassette, indicates beam centering and alignment in a clear, intuitive way. In clinical use, the laser alignment technique provided uniformly high image quality, equivalent to that of fixed equipment. The system has the advantages of being simple to use and inexpensive to implement with existing equipment.

The effect of carbohydrates in milk on the absorption of calcium by postmenopausal women.

The purpose of this investigation was to determine if the presence of carbohydrate in milk, either lactose or its hydrolysis products, enhance the bioavailability of calcium (Ca) in milk. Two studies were performed. In study A, fractional Ca absorption was measured in 11 lactose-tolerant postmenopausal women after an oral dose of 47Ca-equilibrated milk formula containing no carbohydrate (NOCHO), lactose (LACTOSE), or an equivalent amount of glucose plus galactose (SUGAR); all participated in three absorption studies in random order. The NOCHO formula contained 10.0 g protein and 217 mg Ca from a combination of milk mineral and protein isolates; the LACTOSE and SUGAR formulae contained in addition 12 g lactose or 6 g glucose plus 6 g galactose, respectively. In study B, fractional Ca absorption was measured in five postmenopausal women after an oral dose of 47Ca-equilibrated skim milk (217 mg Ca) and lactase-treated milk, each with sufficient carbohydrate added to equal 12 g. For both studies, the increase in forearm radioactivity 4 and 8 hours after oral 47Ca administration relative to the increase observed after IV administration was used to estimate fractional Ca absorption. The addition of lactose but not glucose plus galactose to the NOCHO formula enhanced Ca absorption (p less than 0.05). Fractional absorption at 4 hours was 0.386 from the LACTOSE formula compared with 0.310 for both the NOCHO and SUGAR formulae. Those individuals with the lowest absorption in the absence of carbohydrate had the greatest increase with lactose. In contrast, Ca absorption was the same from skim milk as from lactase-treated skim milk (study B).(ABSTRACT TRUNCATED AT 250 WORDS)

[18F]fluoride from a small cyclotron for the routine synthesis of [18F]2-fluoro-2-deoxy-D-glucose.

[18F]Fluoride was produced via the 18O (p, n) 18F reaction using a low volume stainless steel 18O-water target in a small cyclotron. The average 18F production rate for 60 runs was about 720 microCi/microA-min. A typical bombardment time of 20 min produced 120 mCi of 18F-fluoride. [18F]2-Fluoro-2-deoxy-D-glucose ([18F]2FDG) was prepared using the procedure developed by Tewson [J. Nucl. Med. 24, 718 (1983)] involving a protected cyclic sulfate glucose derivative as precursor. The routine synthesis and quality testing of [18F]2FDG required 1 h and, typically, yields of 30-35 mCi of greater than 95% HPLC-pure product were obtained.

Pharmacologic evidence for specificity of pursuit dysfunction to schizophrenia. Lithium carbonate associated with abnormal pursuit.

Conflicting findings regarding the prevalence of abnormal smooth-pursuit eye movements in patients with major affective disorders call into question the specificity of impaired smooth-pursuit eye movements to schizophrenia. We report that pursuit is impaired in 88% of lithium carbonate-treated affective disorder patients whose pursuit was normal prior to receiving this drug. Over half of lithium carbonate-treated affective disorder patients in remission also showed impairment of smooth-pursuit eye movements. In conjunction with recent prevalence data on family members of psychiatric patients, the findings support the specificity of abnormal pursuit as a biological trait associated with schizophrenia, but not with the major affective disorders. The mechanisms by which lithium carbonate impairs pursuit are discussed.

Effect of meal composition on calcium absorption: enhancing effect of carbohydrate polymers.

Meal components including fat, fiber, and carbohydrates can influence the intestinal absorption of calcium; such interactions may be of even greater importance in the presence of intestinal disease. This study compares intestinal absorption of 47CaCl2 administered in four ways: in water, within a standard meal, with a liquid formula (Ensure, Ross Laboratories, Columbus, Ohio), or with a glucose polymer solution (Frodex-15, Ross). Studies were carried out in 9 patients with ileal resection, 3 patients with jejunoileal bypass, and 14 controls. Fractional calcium absorption from water was lower in patients than in controls. Absorption was enhanced 1.5- to 5-fold when 47CaCl2 was administered with a liquid formula diet containing a glucose polymer or with the glucose polymer alone. Patients with the lowest calcium absorption from breakfast showed the greatest effect of calcium ingestion with formula or glucose polymer. These findings further emphasize the importance of meal composition on calcium absorption and provide a possible mechanism for enhancing calcium absorption in some patients with chronically impaired absorption.

Relatives of unipolar and bipolar patients have normal pursuit.

Impaired smooth pursuit eye movements are significantly less prevalent among the first-degree relatives of patients who have major affective disorders than among the first-degree relatives of schizophrenics. The distribution of normal and abnormal smooth pursuit among the relatives of unipolar and bipolar patients does not differ from that of normal individuals having no family history of major psychosis. Smooth pursuit impairment is thus specific to relatives of schizophrenic patients and is not characteristic of relatives of patients with major affective disorders.

Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys.

Rhesus monkeys were trained to track a moving disk using a procedure in which responses on a lever were reinforced with water delivery only when the disk, oscillating in a horizontal plane on a screen at a frequency of 0.4 Hz in a visual angle of 20 degrees, dimmed for a brief period. Pursuit eye movements were recorded by electrooculography (EOG). IM phencyclidine, secobarbital, and diazepam injections decreased the number of reinforced lever presses in a dose-related manner. Both secobarbital and diazepam produced episodic jerky-pursuit eye movements, while phencyclidine had no consistent effects on eye movements. Lever pressing was disrupted at doses which had little effect on the quality of smooth-pursuit eye movements in some monkeys. This separation was particularly pronounced with diazepam. The similarities of the drug effects on smooth-pursuit eye movements between the present study and human studies indicate that the present method using rhesus monkeys may be useful for predicting drug effects on eye tracking and oculomotor function in humans.

Abnormal-pursuit eye movements in schizophrenia. Evidence for a genetic indicator.

Disordered smooth-pursuit eye movements occur in a high percentage of schizophrenic patients and their first-degree relatives. A Test of the hypothesis that these disorders represent a genetic indicator of schizophrenia was undertaken by testing pursuit eye movements in a sample of monozygotic and dizygotic twins discordant for clinical schizophrenia. Deviant eye tracking is significantly concordant within monozygotic twin pairs, and less so with dizygotic twin pairs discordant for schizophrenia. A genetic interpretation is consistent with these results.