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R Moncayo

Publications and source records attributed to R Moncayo.

At least 19 recordsLinked to original sources

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

Adult↗

Thallium-201 gated single-photon emission tomography for the assessment of left ventricular ejection fraction and regional wall motion abnormalities in comparison with two-dimensional echocardiography.

Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n = 55) or pharmacological stress (n = 17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r = 0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r = 0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n = 23), these correlations were even better (r = 0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%-100% and 82%-98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.

Female↗

One year's clinical experience of 18F-FDG PET with a modified SPET camera using molecular coincidence detection.

High-quality positron emission tomographic (PET) cameras are expensive and, therefore, not available in many centres. To allow access to clinical 18F-fluorodeoxyglucose (18F-FDG) PET, we began working with an ADAC Vertex camera equipped with a molecular coincidence detection (MCD) module in February 1997. Here we give a preliminary assessment of the clinical utility of our approach. To date, 109 studies have been performed in MCD-mode using standardized protocols (99 oncology cases, 10 neurology cases). Twenty-eight cardiological and 15 other studies were performed using 511 keV collimators without attenuation correction. The average dose of 18F-FDG for MCD studies was 150 MBq, thus avoiding overloading the detectors; cardiac studies required 370 MBq. The results obtained were carefully compared with computed tomography, magnetic resonance imaging, myocardial perfusion scans, coronary angiography and conventional radiology. The results were compared on a patient basis, including histology, surgical notes, autopsy reports and follow-up data. Oncological studies were performed to assess malignancy in a particular lesion (n = 22), staging of cancer (n = 57) or to evaluate whether therapy had been successful or not (n = 20). Indications for conducting studies were categorized as appropriate (Ia) or adequate (Ib). For Ia category cases, the results were: true-positive = 31, true-negative = 12 and false-positive = 2. For Ib category cases, the corresponding figures were: true-positive = 18, true-negative = 10, false-positive = 3 and false-negative = 1. False-positive studies were a result of inflammatory disease or artefacts. Six cases with temporal lobe epilepsy were correctly identified. In cardiac studies, we also found a good correlation with clinical parameters (i.e. hibernating myocardium or scarred tissue). Altogether, this cost-effective set-up allows nuclear medicine institutions to obtain valuable data in clinical practice with a system used both for single photon emission tomography and PET.

Coronary Disease↗

Vascular endothelial growth factor in serum and in the follicular fluid of patients undergoing hormonal stimulation for in-vitro fertilization.

A cross-sectional study regarding endocrine and cytokine parameters in human follicular fluid (FF) as compared to serum values following hormonal stimulation for in-vitro fertilization was conducted. The patients (n = 32) were treated sequentially with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin followed by a combination of buserelin plus highly purified follicle stimulating hormone and finally human chorionic gonadotrophin, in order to induce ovulation. The FF content of pro-inflammatory (IL-1, IL-6), and anti-inflammatory (IL-1ra, IL-10) cytokines, of the immune response-related soluble interleukin-2 receptor (sIL-2R), as well as the mitogens vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) were determined. Routine evaluation included peripheral blood cell counts, morphological data of the ovary and ova, ovarian steroids, prolactin concentrations and thyroid function parameters [free thyroxine (fT4), thyroglobulin]. The concentrations of IL-6, IL1-ra, sIL-2R, VEGF and bFGF in the FF compartment were higher than in serum in the majority of cases. Regression analysis showed a significant association between the serum and FF concentrations of fT4 (P = 0.04; y = 0.37 + 0.34x) and IL-6 (P = 0.002; y = 0.78 + 0.5x). Multiple regression analysis revealed that progesterone played a role in determining VEGF concentrations in the FF (P = 0.07; y = 0.37 + 0.86x). Thyroglobulin concentrations within the FF were extremely low, whereas fT4 concentrations in the FF were similar to those in serum. Patients with a previously diagnosed hypothyroidism tended to have lower serum oestradiol and higher serum progesterone when compared to euthyroids. We conclude that the human FF represents a functional compartment that integrates endocrine, immunological, and mitogenic signalling that is unique for each ovarian follicle. The close association between progesterone and VEGF within the FF suggests a close association of this mitogen to gonadotrophin stimulation, confirming the ovary as a production site of VEGF.

Adult↗

Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Aged↗

Evaluation of immunological mechanisms mediating thyroid-associated ophthalmopathy by radionuclide imaging using the somatostatin analog 111In-octreotide.

Thyroid associated ophthalmopathy (TAO) is a disorder involving the soft tissues and extraocular muscles of the orbit seen mainly in cases of Graves' disease. Although an immunogenic pathogenesis has been proposed, the actual mechanisms of the in vivo retrobulbar involvement are not well defined. The recent introduction of the 111In-labeled somatostatin analog, octreotide, which can bind in vivo to the cell membrane of activated lymphocytes expressing somatostatin receptors, has provided a new investigational tool for diseases with a presumed immunological background. Based on this property, octreotide scans can be expected to be positive in cases of immunological disease showing tracer accumulation within affected sites. The aim of this study was to evaluate the utility of scintigraphic imaging with octreotide of the retrobulbar space in cases of TAO, including sequential studies of patients undergoing immunosuppressive therapy. We studied a series of 51 patients who had Graves' disease with varying degrees of TAO. Nine patients had received immunosuppressive therapy. The degree of orbital inflammation was classified according to the clinical activity score of Mourits. Both planar and tomographic imaging of the orbit were carried out using 111 MBq of the 111In-labeled octreotide (OctreoScan) 2 h after tracer injection. A significant tracer accumulation in the retrobulbar space was seen in all 20 patients with a high activity score, in 8 of 16 cases with a negative score, and in 11 of 20 cases with an intermediate Mourits' score. In cases of persistent eye disease in spite of immunosuppressive therapy, the octreotide scan remained positive. Successful therapy either with prednisolone, external radiation, or i.v. immunoglobulins showed a significant diminution of tracer uptake after finishing the therapeutic regime. Three-dimensional reconstruction of the images also revealed a significant tracer accumulation in the areas of the lacrimal gland, the nasal region, and the pituitary. Controls cases (n = 30) showed no uptake in the orbital region. We conclude that 111In octreotide scintigraphy is an objective method that identifies patients with active inflammatory eye disease, i.e., having significant tracer uptake in the retrobulbar space. This uptake appears to reflect an immunological process, since immunosuppressive therapy will significantly decrease tracer accumulation.

Adult↗

Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country.

Iodized salt prophylaxis has been performed in Austria since 1963. Through this approach, mean urinary iodine excretion has been normalized to 144+/-23.5 microg/g creatinine per day. Thus Tyrol is no longer an endemic goiter area. We have analyzed the impact of iodized salt prophylaxis on thyroid cancer (TC) comparing data from the early 1960s with those corresponding to the period 1986 to 1995, when iodine supply was normalized. The study included 439 patients from Tyrol and Southern Tyrol. The incidence of TC in Tyrol has risen during the past decades from 3.07 between in 1957 and 1970 to 7.8 between 1990 and 1994 (CR/100000/year). We observed a rise in the percentage of differentiated adenocarcinomas (56% to 91.5%) with a predominance of papillary TC (54.4%) along with a decrease of anaplastic TC. In addition to these histological features, a shift to less advanced TNM stages, eg, T1-3, N0-1a, M0, was obvious, increasing from 29% to 72.2%, whereas advanced tumors, ie, T4 or N1b or M1, decreased from 71% to 28%. These changes have significantly improved prognosis. The current 5-year survival rate is 90.7% as compared with a rate of 73% in the 1960s; the values for 7-year survival are 89% and 48%, respectively. The marked effects of age, tumor stages, and histology on prognosis were confirmed with the Kaplan-Meier method. We conclude that together with normalization of iodine supply in an endemic goiter region the epidemiological profile of TC has changed. Even though the incidence of TC has risen, prognosis has significantly improved due to a shift towards differentiated forms of TC that are diagnosed at earlier stages.

Age Factors↗

Whole-body scintigraphy with 99Tcm-MIBI, 18F-FDG and 131I in patients with metastatic thyroid carcinoma.

We assessed the relative usefulness of whole-body planar scintigraphy with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI), 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG-RS) rectilinear scanning and with diagnostic and therapeutic doses of 131I, for the detection of local recurrences and metastatic lesions in 12 patients with thyroid carcinoma and elevated thyroglobulin serum levels. All images were evaluated independently by three experienced observers to define the number and location of metastatic lesions. 18F-FDG-RS and 99Tcm-MIBI scintigraphy provided similar results, but the tracer that allowed the detection of the highest number of metastases was 99Tcm-MIBI. Both 99Tcm-MIBI scintigraphy and 18F-FDG-RS appear to be more sensitive than 131I scintigraphy for the detection of metastases of thyroid carcinoma. Tomographic acquisitions were also performed on a limited field of view in each subject and, as expected, 18F-FDG-PET was more sensitive than 18F-FDG-RS. 99Tcm-MIBI scintigraphy, a widely available and relatively non-expensive technique, therefore sems suitable for the assessment and follow-up of patients with metastatic thyroid carcinoma and does not require the withdrawal of hormone therapy for lesion imaging.

Adenocarcinoma, Follicular↗

Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels.

To study the influence of thyroid hormone on Lp(a) plasma concentration we measured Lp(a), total cholesterol, LDL-C, HDL-C, triglycerides and fT4 levels and determined apo(a) phenotypes in 26 patients with hyperthyroidism in a follow-up study before and after thyreostatic treatment. The pretreatment values of total cholesterol (TC), LDL-C, and Lp(a) were significantly reduced as compared with those of healthy controls. The reduced mean Lp(a) concentrations could not be explained by a difference of apo(a) 'size allele' frequencies between patients and controls. During thyreostatic treatment mean concentrations of TC, LDL-C, and HDL-C increased significantly. The mean Lp(a) value was not changed after 4 weeks of treatment. The individual changes of Lp(a), however, correlated significantly with those of LDL-C levels (R = 0.40, P = 0.04). Eighty-one per cent of the patients showed an increase of Lp(a) or no change of the Lp(a) level and 19% reacted with a decrease upon thyreostatic treatment. The observed lipid and lipoprotein changes were not different in patients with Graves disease or multifocal toxic goiter. The results indicate that Lp(a) plasma levels are decreased in the hyperthyroid state irrespective of the pathogenic mechanism.

Adolescent↗

Perspectives on ovarian dysfunction and autoimmunity.

Recent research has documented the fact that a series of factors appear to play an important role during early phases of ovarian formation and function. Within the field of reproductive medicine some of the areas of future research will encompass genetical aspects, the influence of local regulatory growth factors, the role of innervation, the role of the resident immune cells, and the potential role of hCG. The influence of these factors can be studied in animal models.

Animals↗

Endocrine ophthalmopathy in a patient under continuous immunosuppressive therapy after cardiac transplantation.

We present the case of a female patient who has been on immunosuppressive therapy consisting of cyclosporin A and prednisolone for 9 years because of heterotopic (auxiliary) heart transplantation in 1984. In 1992 the patient developed Graves' disease followed by endocrine ophthalmopathy class IV 1 year later. To our knowledge this is the first report on Graves' disease with subsequent severe endocrine ophthalmopathy in a patient under immunosuppressive treatment with cyclosporin A and prednisolone in doses that effectively prevent heart transplant rejection. Prednisolone, which is used as a first line treatment of endocrine ophthalmopathy, and cyclosporin A, both inhibit T cell function. However, in this patient they were not effective in preventing the development of Graves' disease with subsequent endocrine ophthalmopathy, both of which are autoimmune diseases.

Adult↗

A new endocrinological and immunological syndrome in SLE: elevation of human chorionic gonadotropin and of antibodies directed against ovary and endometrium antigens.

We have analysed the levels of gonadotropins in male and female patients with systemic lupus erythematosus (SLE). Human chorionic gonadotropin hCG was elevated in 23.8% of patients compared with 12.7% of controls. hCG isolated from the serum of SLE patients was bioactive in vitro. Levels of hCG were significantly correlated with those of its beta-subunit but not with the levels of follicle stimulating hormone, luteinizing hormone, prolactin alphafetoprotein or carcino embryonic antigen. A high percentage of patients presented an organ-specific humoral immune response against ovarian (26.7%) and endometrial (40%) antigens compared with controls (8% and 7.6%, respectively). Endometrial antibodies were significantly correlated to the levels of prolactin. The ovarian tumour marker CA-125 was elevated in 32.5% of patients, including two males. As a whole, these elements delineate a new endocrine and immunological syndrome in SLE in which the elevation of hCG could provide a central physiological explanation for a series of endocrine alterations that characterize this disease.

Adolescent↗

Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results.

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions.

Arthritis, Psoriatic↗

Autoimmunity and the ovary.

The ovary was first documented as a target of autoimmunity over three decades ago yet today the aetiology and pathogenesis of autoimmune-mediated premature ovarian failure (POF) are poorly understood. Here, Roy and Helga Moncayo provide a brief overview of human autoimmune-mediated POF and the animal models of POF. They propose a model for the development of the disease, highlighting the role of supraphysiological levels of gonadotropins in inducing selectively antigenic mature ovarian elements.

Animals↗