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Biomedical subjects

T Greitz

Publications and source records attributed to T Greitz.

At least 37 records · Page 2Linked to original sources

11C-labeled 4-isopropylantipyrine: preparation and biological evaluation as a blood flow tracer in positron emission tomography (PET).

Radiolabeled 4-isopropylantipyrine (1) has been synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.62 +/- 0.03 (mean +/- SE). Autoradiographic determination of regional cerebral blood flow under normal flow conditions indicated that [14 C]-1 gives results essentially identical with those obtained with the widely used tracer [14C]-4-iodoantipyrine ( [14C]-IAP). Studies performed in high-flow states indicated that [14C]-1 is not more diffusion limited than [14C]-IAP. A rapid synthesis was therefore developed for the preparation of [11C]-1. Radiochemical yields were increased to 40-50% when the alkylation of 2 with [11C]methyl iodide was performed in dimethyl sulfoxide using solid potassium hydroxide as a base. Since the 11C-labeled compound can easily be produced in large quantities and since the tracer is not diffusion limited at flow rates commonly observed in normal and most pathological states in man, [11C]-4-isopropylantipyrine will be used for in vivo studies of CBF using positron emission tomography.

Animals

Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.

Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders.

Animals

Effects of prenalterol and volume loading with dextran on haemodynamics and oxygen consumption in dogs during high epidural block with special reference to the splanchnic region.

High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 +/- 2.9 to 12.0 +/- 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre-epidural values. Volume loading with dextran 10 ml X kg-1 b.w. increased QT nearly to the pre-epidural value. SVR decreased further to 61% of the pre-epidural value and AP was only slightly increased to 14.9 +/- 2.7 kPa. Subsequent administration of prenalterol 20 micrograms X kg-1 b.w. caused a further increase in QT to 17% above the pre-epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre-epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (Qpv) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in OT must therefore have favoured other vascular beds. Hepatic and pre-portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole-body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre-epidural level following volume loading in combination with prenalterol.

Animals

Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using [68Ga]EDTA, [11C]glucose, and [11C]methionine.

A patient with an anaplastic (malignant) astrocytoma was examined with computed tomography (CT) and with positron emission tomography (PET), in the latter case using [68Ga]EDTA, [11C]glucose, and [11C]methionine. The CT examination as well as the [68Ga]EDTA study showed a small tumor located in the region of the head of the left caudate nucleus. The [11C]glucose examination showed increased uptake on the same region, as did the [11C]methionine examination, but the latter also showed a considerable uptake in the entire left thalamic region. The patient died 15 days after the [11C]methionine study and a histologic evaluation of thin sections obtained at autopsy showed excellent agreement between tumor extent and activity distribution after [11C]methionine administration. The tumor tissue seen only with [11C]methionine was histologically different from that part of the tumor observed with the other tracers. Although cytologically similar, the latter showed large necrotic areas and an ability to induce marked endothelial proliferation, whereas in the former neither necroses nor notable endothelial proliferation was seen. In this case more than 50% of the tumor would have remained radiologically imperceptible without the [11C]methionine PET examination.

Astrocytoma

Effect of dexamethasone treatment on peritumoral brain edema: evaluation by computed tomography.

In a prospective study, the effect of dexamethasone treatment on brain edema was evaluated by computed tomography (CT) in 14 patients with intracranial neoplasm. A CT study was made immediately prior to the beginning of the treatment and at various intervals for 8 to 19 days thereafter. The volume and attenuation of the edema were measured and related to the time after the start of treatment. In five cases of meningioma, only minor changes were shown; the edema volume either decreased or increased slightly or did not change at all. In four gliomas, a substantial decrease was noted in the edema volume in two cases and a smaller decrease was observed in two cases. In three metastases, a linear decrease in edema volume was noted during the entire follow-up, reducing it to one-fourth of the initial volume after 2 weeks of treatment. In one case of acoustic neuroma and in one undiagnosed lesion, a marked decrease in edema volume was also noted. The attenuation of the remaining edema was constant during the entire treatment time.

Adult

Diagnosis of sellar and parasellar lesions by computed tomography.

Suspected lesions in and around the sella were examined by CT in 129 cases. The diagnostic accuracy and various technical aspects of the method are described. The mean attenuation and enhancement after administration of contrast material are evaluated in craniopharyngiomas, chromophobe adenomas, meningiomas, aneurysms, dermoid cysts, an arachnoid cyst and a glioma. the choice of collimator and its use in relation to sellar dimensions, particularly the sellar depths, are emphasized.

Diagnosis, Differential

Attenuation changes of the ventricular CSF after intravenous injection of contrast material.

The CT attenuation change of the intraventricular CSF after i. v. administration of contrast material has been studied in 20 patients. A very small increase of attenuation was observed in the entire material. The method does not seem to be appropriate at present for the study of small attenuation changes in the CSF reflecting the passage of contrast material.

Adolescent

A ring detector positron camera system: its merits: clinical experience.

A ring detector positron camera system for CT of the brain is described. The system uses 95 NaI (Tl) detectors, arranged with cylindrical geometry, for the simultaneous detection of coincidences from 1,900 detector combinations. With a new sampling technique an experimental system resolution of 7 mm FWHM has been obtained. The sensitivity was found to be 5,300 c/s with a 100-keV energy threshold and using a 19.2-cm-diameter cylindrical phantom with a homogeneous specific activity of 1 muCi/cm3. A clinical study of blood-brain barrier damage using 68Ga-EDTA is reported.

Brain

Stereotactic computer tomography for biopsy of gliomas.

A technique is introduced enabling automatic transfer of coordinates obtained at computer tomography into a stereotactic system previously applied in biopsies of brain lesions. Four to five biopsies from different parts of gliomas were taken to compare the structures demonstrated on computer tomography with the microscopic appearances. Of 45 biopsies in 13 patients, 36 were predicted correctly. This also served as an attempt to classify gliomas on the basis of their appearance in the CT image.

Adolescent