Single photon emission tomography assessment of cerebral dopamine D2 receptor blockade in schizophrenia.
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Biomedical subjects
Publications and source records attributed to B J Shepstone.
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A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.
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Ten patients with suspected primary, recurrent or metastatic medullary carcinoma of the thyroid (MCT) were studied prospectively with Tc-99m(V) DMSA. Of these, two patients had primary disease, seven patients were asymptomatic but had persistent and serial elevations in serum calcitonin following previous thyroid resections for MCT, and one asymptomatic patient with normal serum calcitonin was studied because of suspected hilar nodes metastases. The serial calcitonin peak in the patients was 0.04-43ng/ml (normal less than 0.08ng/ml). Scintigraphy was considered positive in seven of the asymptomatic patients and equivocal in one. The two patients with primary disease had increased uptake before but not after thyroidectomy. Primary disease, localized recurrence and distant metastases in soft tissue (nine patients) and bone (one patient) were detected in these patients, and this resulted in early surgical resection (five patients) and radiotherapy (one patient). We conclude that Tc-99m(V) DMSA is a useful imaging agent in the evaluation of asymptomatic MCT patients with hypercalcitonemia.
Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.
Twenty-eight women with suspected endometriosis or infertility, or both, received radiolabelled monoclonal antibody OC-125 F(ab')2 fragments before surgery in a study to determine whether foci of pelvic endometriosis could be displayed with immunoscintigraphy. Immunoscintigraphy was positive in 22 women (16 with endometriosis, two with pelvic adhesions, one with pelvic inflammatory disease and one with normal pelvic findings) and negative in five women (two with endometriosis and three with normal pelvic findings). One woman developed a hypersensitivity reaction and, therefore, did not receive the radiolabelled fragments. The method had 89% sensitivity and 33% specificity for the diagnosis of endometriosis; it had 91% sensitivity and 60% specificity for the diagnosis of benign pelvic disease.
Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population.
Radioimmunodetection has been shown to be an invaluable method in the diagnosis of primary and metastatic malignant disease. Fourteen patients, consisting of four men and 10 women with clinical suspicion of metastatic malignant melanoma or ocular melanoma were prospectively evaluated with the technique. Ten (71%) had positive and four (29%) had negative scintigrams. There was one false-positive scintigram. The overall sensitivity and specificity were 100% and 80%, respectively. SPET was necessary for the radioimmunodetection of patients with ocular melanoma. Combined immunoscintigraphy and immunolymphoscintigraphy enhanced the diagnosis of small, cutaneous melanoma and metastatic lymph node disease.
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Whole body scintigraphy with [99mTc] (v)dimercaptosuccinic acid (pentavalent DMSA) was performed in seven patients with histologically confirmed medullary carcinoma of the thyroid (MCT). Six of these patients had undergone previous thyroid resections for MCT and, although asymptomatic at the time of pentavalent DMSA scintigraphy, had persistent and serial elevations in their plasma calcitonin levels. One additional patient was scanned before and after total thyroidectomy for MCT. The pentavalent DMSA scintigram demonstrated either local neck recurrence (three patients) or distant metastases (two patients) in five of the six asymptomatic patients. In one asymptomatic patient only equivocal neck uptake was demonstrated. Since he had only minimal calcitonin elevations, repeat neck exploration was not performed. The one patient studied before thyroid resection for MCT demonstrated neck uptake before, but not after, total thyroidectomy. The results of the scintigrams had significant impact on patient care and resulted in neck re-exploration (three patients), neck biopsy (one patient), and lumbar spine biopsy and subsequent radiotherapy (one patient). These data demonstrate pentavalent DMSA to be a sensitive localizing agent in the evaluation of asymptomatic MCT patients with hypercalcitonaemia. Accurate targeting of treatment may be shown in due course to have a beneficial impact on survival.
Five patients with Rasmussen's syndrome (sometimes known as smouldering encephalitis), are presented. This rare form of childhood epilepsy is characterized by intractable partial seizures with progressive neurological and mental impairment. Diagnostic brain biopsy shows the histological changes of active encephalitis, consistent with a viral infection. Although the raised cerebrospinal fluid (CSF) complement and interferon levels seen in some patients support this hypothesis, no infective agent has yet been isolated. All five patients were investigated by transmission computed tomography (CT) of the head, electroencephalography (EEG) and cerebral single-photon-emission computed tomography (SPECT) using 99Tcm-hexamethylpropylenamine oxime (HMPAO) and in addition 123I-amphetamine (IMP) in Patient 1. 99Tcm-HMPAO is now regarded as reflecting cerebral perfusion, whereas the uptake of 123I-amphetamine is more dependent on cell function. In all patients SPECT imaging demonstrated an area of hypoperfusion/hypometabolism which corresponded to the anatomical localization of the epiletogenic foci found by clinical assessment, EEG and CT. In all cases the SPECT study also demonstrated a more extensive area of abnormality than CT, and in the two patients who had sequential studies, alteration in the size of the defect was found which correlated with the patients' changing clinical condition. SPECT imaging in Rasmussen's syndrome may facilitate anatomical localization of the area of pathology, and may demonstrate a changing pattern in cerebral hypoperfusion/hypometabolism. It could also serve as a guide to accurate brain biopsy.
Forty-five 131I-MIBG scintigrams were performed in 42 patients with suspected phaeochromocytoma. Two patients were infants and the remainder were adults. A sensitivity of 81.8% and a specificity of 88.2% were achieved, leading to an accuracy of 86.7%. The positive predictive value was 69.2% and the negative predictive value was 93.7%.
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Among 10 patients with endometriosis CA 125 was increased (greater than 35 U/ml) in endometriotic cyst fluid in all the patients, but only two had increased serum concentrations. Gel electrophoresis of serum, endometriotic cyst fluid, and endometriotic tissue resolved the CA 125 immunoreactive fragments from the three sources into bands of similar electrophoretic mobilities. Electrophoresis under reducing and non-reducing conditions showed immunoreactive fragments of apparent masses of 55,000 and 140,000 daltons, respectively. Analysis under reducing conditions did not result in loss of activity. CA 125 antigen is thought to be a high molecular weight glycoprotein complex. As far as is known, this is the first report describing lower molecular weight immunoreactive determinants of CA 125.
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CA-125 is a membrane antigen detected in the serum of some women with gynaecological disease including endometriosis. We attempted to use a radioiodinated anti-CA-125 monoclonal antibody, OC-125, to image ovarian endometriosis using immunoscintigraphy. Two women with significant endometriosis and normal serum CA-125 levels had positive immunoscintigraphy. In one woman, all areas of endometriosis were imaged; in the other, endometriosis in one affected ovary was seen, but uptake in the other ovary was less than the extent of the disease.
This paper reviews the development of cerebral scintigraphy from its early days of planar imaging with simple technetium-99m labelled compounds to the recent revival of the technique in the form of positron-emission and single-photon emission tomography. A short explanation of instrumentation and radiopharmaceuticals is given as a prelude to a description of both techniques in normal and pathological situations. Particular emphasis is placed on the more readily-available single-photon emission-tomographic techniques using labelled amines in the functional investigation of disorders not readily diagnosed by computed tomography.