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Biomedical subjects

F Fazio

Publications and source records attributed to F Fazio.

At least 127 records · Page 7Linked to original sources
PubMed1997

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels.

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of 111In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 microg octreotide s. c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of 111In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of 111In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 microg octreotide s. c. caused a significant reduction in TSH levels from 4.8+/-1.4 mU/l to a nadir of 3.1+/-1.1 mU/l after 6 h (P<<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that 111In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.

Adenoma↗
PubMed1997

Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone.

The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

Adenoma↗
PubMed1997

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography.

Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue.

Adult↗
PubMed1997

Combination of monoclonal antibodies for radioimmunoguided surgery.

The use of a cocktail of monoclonal antibodies in intraoperative radioimmunodetection of colorectal tumour has been evaluated in 14 patients. Eight patients had primary and six recurrent colorectal cancer. Three different monoclonal antibodies were used included B72.3, recognizing TAG72 antigen, FO23C3 and FO23C5 directed against two epitopes of CEA. The antibodies were labeled with 125I. During surgery the radioactive emission of tumour and normal tissue was evaluated by a gamma detecting probe. Ten patients showed positive intraoperative results and in particular 6 (75%) of the 8 patients with primary tumour and 4 (67%) of the 6 patients with recurrence, with a mean tumour to normal tissue ratio of 2.2. Intraoperative radioimmunodetection was instrumental in modifying the therapeutic approach in two patients with recurrent cancer but in none of the patients with a primary presentation. Immunohistochemical analysis, to evaluate TAG72 and CEA antigen expression, was performed in 13 cases. CEA antigen was expressed in 8/13 cases and TAG72 in 5/13. Thus the sensitivity was 38.5% and 61.5% with B72.3 and anti-CEA monoclonal antibodies respectively, while in combination the sensitivity was 71.4%. The use of a cocktail of different antibodies improved the sensitivity of intraoperative radioimmunodetection of colorectal tumours, when compared with a single antibody injection. This approach might improve the clinical use of radioimmunodetection.

Adult↗
PubMed1997

Naming deficit for non-living items: neuropsychological and PET study.

We report a patient with progressive left hemisphere atrophy who presented a lexical retrieval deficit more pronounced in naming non-living items than in naming living items. Word frequency and familiarity strongly influenced the performance, but the dissociation persisted when the items were controlled for these factors. In addition, the prevalent deficit for non-living items in respect to living items could be confirmed in tasks where other patients presented the opposite pattern. A PET study showed a significant hypometabolism in the left hemisphere regions suggesting that, at variance with living deficit which is observed in patients with bilateral lesions, non-living deficit is produced by unilateral left hemispheric lesions. This patient confirms that living and non-living categories may dissociate and that distinct neural systems subsume their knowledge.

Aged↗
PubMed1997

Synthesis of [O-methyl-11C]fluvoxamine--a potential serotonin uptake site radioligand.

5-Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-O-(2-aminoethyl)oxi me (fluvoxamine), a potent clinically used antidepressant, was labelled with carbon-11 (t1/2 = 20.4 min) as a potential radioligand for the non-invasive assessment of serotonin uptake sites in the human brain with positron emission tomography (PET). The two-step radiochemical synthesis consisted of O-methylation of an amino-protected desmethyl precursor with [11C]methyl iodide under mild conditions in the presence of tetrabutylammonium hydroxide in acetonitrile, followed by deprotection with trifluoroacetic acid. 5-[11C]Methoxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-O-(2-aminoethy l) oxime was obtained in > 98% radiochemical purity in 40 min with a radiochemical yield of 4 +/- 2% (non-decay corrected) and a specific radioactivity of 1 +/- 0.5 Ci/mumol. 5-Hydroxy-1-[4-(trifluoromethyl)-phenyl]-1-pentanone-O-[2- (tert-butoxycarbonylamino)ethyl]oxime, the precursor for the radiosynthesis of [11C]fluvoxamine, was prepared by a convenient three-step synthesis from the pharmaceutical form of fluvoxamine maleate by converting it into the free base, demethylation by trimethyliodosilane and introduction of the BOC-protective group with di-tert-butyl dicarbonate.

Binding Sites↗
PubMed1997

Brain activity during observation of actions. Influence of action content and subject's strategy.

PET was used to map brain regions that are associated with the observation of meaningful and meaningless hand actions. Subjects were scanned under four conditions which consisted of visually presented actions. In each of the four experimental conditions, they were instructed to watch the actions with one of two aims: to be able to recognize or to imitate them later. We found that differences in the meaning of the action, irrespective of the strategy used during observation, lead to different patterns of brain activity and clear left/right asymmetries. Meaningful actions strongly engaged the left hemisphere in frontal and temporal regions while meaningless actions involved mainly the right occipitoparietal pathway. Observing with the intent to recognize activated memory-encoding structures. In contrast, observation with the intent to imitate was associated with activation in the regions involved in the planning and in the generation of actions. Thus, the pattern of brain activation during observation of actions is dependent both on the nature of the required executive processing and the type of the extrinsic properties of the action presented.

Adult↗
PubMed1997

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↗
PubMed1997

Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting.

Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (90Y) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of 90Y through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of 90Y bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and 90Y-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of 90Y was observed in animals administered 90Y-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of 90Y-DAPA-biotin. Despite the lower levels of accumulation in the tumour after injection of 90Y-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of 90Y-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal 90Y-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.

Adenocarcinoma↗
PubMed1997

Myocardial viability assessed with fluorodeoxyglucose and PET in patients with Q wave myocardial infarction receiving thrombolysis: relationship to coronary anatomy and ventricular function.

In previously thrombolysed patients, we analysed residual myocardial viability using the PET-FDG technique and correlated its presence and extent to the angiographic appearance of the infarct-related vessel and left ventricular function. Thirty-six patients who had undergone intravenous thromboloysis for acute myocardial infarction 4.8 +/- 7.2 months previously were studied. Coronary angiography, left ventriculography, and assessment of myocardial perfusion and metabolism were all performed within 1 week. All patients exhibited perfusion defects consistent with the clinically identified myocardial infarction site. Residual viability, as assessed by the PET-FDG technique, was present in 53% of cases. The infarct-related coronary artery was patent in 19 (53%) patients (TIMI grade 3, 79%); of the remaining 17 with occluded infarct-related arteries, 11 had collaterals to the infarct area. Significant FDG uptake was observed in 63% of patients with a patent infarct-related artery and in 41% of those with an occluded infarct-related artery. The same study protocol was adopted in a control group of 30 patients with myocardial infarction who did not receive thrombolysis. The number of infarct-related patent vessels was significantly lower in these patients (30 vs 53%) (TIMI grade 3, 56%), but the overall percentage of PET viability was again 53%. Qualitative analysis of the regional perfusion pattern showed that the magnitude and severity of the perfusion defect was similar in the two groups, regardless of the presence or absence of FDG uptake. Global left ventricular function was also similar in the two groups. However, regional wall motion was significantly better in the thrombolysed patients with a patent infarct-related artery than in those who had not received thrombolysis and whose culprit vessel was also patent. In conclusion, the results of our study support the notion that early recanalization of the infarct-related artery is critical for preserving left ventricular function. Although the number of patent infarct-related coronary arteries is greater and left ventricular function is better in successfully thrombolysed patients, the regional metabolic pattern does not apparently correlate with the patency of the infarct-related artery. This suggests that, in "chronic' myocardial infarction, residual tissue viability as assessed by fluorodeoxyglucose uptake does not necessarily correlate with coronary recanalization.

Blood Glucose↗
PubMed1997

Oestrogen receptors in meningiomas: a correlative PET and immunohistochemical study.

There have been a number of indications that sex hormones can affect the rate of growth of meningiomas during pregnancy. The presence of oestrogen or progesterone receptors in meningiomas and the influence of sex hormones upon cell cultures derived from human meningiomas have been extensively investigated. The results have been controversial, with most of the discussion centring upon the presence and possible role of oestrogen receptors. The aim of the present study was to assess oestrogen receptors in human meningiomas with 16alpha[l8F]fluoro-17beta-oestradiol ([18F]FES) and positron emission tomography (PET). With this purpose in mind, we measured the regional brain uptake of [18F]FES in six patients with a neuroradiological and histological diagnosis of meningioma, comparing the in vivo PET data with the immunohistological analysis of oestrogen receptors performed on formalin-fixed, paraffin-embedded tissue obtained at surgery. Two analyses were used for the in vivo measurement of [18F]FES binding to oestrogen receptors: the ratio of tumour activity to that of normal tissue (T/NT), calculated 90 min after tracer injection, and the ratio between the equilibrium distribution volume (DV) in normal and pathological tissues, calculated by means of a graphical kinetic analysis. PET studies demonstrated a marked uptake of [18F]FES by the tumour in four of the six patients. Immunohistochemical assay using a manual staining method capable of detecting oestrogen receptors at a level of > 10 pmol mg(-1) of protein detected only sparse immunostaining in one of the six meningiomas. Distinct albeit weak immunostaining was demonstrated in five of the six meningiomas when the sensitivity of the immunohistochemical assay was increased to < 10 pmol mg(-1) of protein by use of an automated staining method (Bioteck 1000). Comparison of the in vivo and immunohistochemical results showed a correlation in five of the six patients, thus indicating the high sensitivity of [18F]FES for the in vivo evaluation of oestrogen receptor expression.

Adult↗
PubMed1997

Diagnostic accuracy and predictive value of 201T1 SPET for the differential diagnosis of cerebral lesions in AIDS patients.

The use of 201T1 has been proposed for the differential diagnosis of lymphomas and non-neoplastic brain masses in AIDS patients. The aim of this study was to assess the diagnostic accuracy of three different semi-quantitative methods for the analysis of 201T1 SPET brain images in individuals with AIDS and brain lesions. Thirty-seven AIDS patients with contrast-enhancing brain lesions underwent 201T1 SPET. Three different lesion-to-background uptake indices were calculated: (1) small lesion/large background (SL/LB; i.e. counts in a 3 x 3 pixel ROI in the lesion/counts in a 7 x 7 pixel ROI in the contralateral healthy hemisphere); (2) small lesion/multiple small background (SL/MSL; i.e. counts in a 3 x 3 pixel ROI in the lesion/average counts of ten 3 x 3 ROIs over the highest background pixel values); (3) large lesion/large background (LL/LB; i.e. counts in an elliptic ROI in the lesion/counts in a contralateral mirrored ROI). Data analysis included a ROC curve analysis to identify the cut-off value corresponding to the highest accuracy value, and an analysis of the predictive value to classify the patients in three categories (high, intermediate and low risk of lymphoma). The greatest accuracy (71%) was achieved with the LL/LB method of analysis. Using this method, 62% of patients could be classified as either having lymphoma or not, whereas 38% could not be classified. LL/LB values > or = 2.9 are suggestive of the presence of lymphomas, whereas values < or = 2 are highly predictive of the presence of a lesion other than lymphoma. However, LL/LB values between 2 and 3 are not diagnostic and adjunctive tests should be carried out. In conclusion, 201T1 SPET was an adequate diagnostic tool in approximately 70% of the cases in this study.

AIDS-Related Opportunistic Infections↗
PubMed1997

Evaluation of pre- and post-reconstruction count-dependent Metz filters for brain PET studies.

In this study we evaluated pre- (PR-R) and post-reconstruction (PO-R) count-dependent Metz filters for PET brain studies in order to increase signal-to-noise ratio. A set of studies using a 3D Hoffman brain phantom was performed at various count levels, and a reference image set was created from extremely high count images. Several combinations of PR-R and PO-R filtering were considered to find the optimal means of processing, including: Hann filter alone; PR-R Metz filter without or with a PO-R low pass filter; and PO-R Metz filter without or with a PR-R low pass filter. A formula was established to correlate the optimal PO-R Metz filter order with the net counts. Resolution [full width at half-maximum (FWHM) and fill width at tenth maximum (FWTM)], normalized residual mean square differences (NRMSD) between the ideal and the processed images, noise reduction and contrast were used as parameters for the evaluation of the different filter combinations. Resolution is decreased by all filter combinations that can effectively control noise; however, FWTM increases less than FWHM. NRMSD indicates that the use of Hann and (optimal) PO-R Metz filter is the most powerful combination from among those tested. A close correlation (r = 0.969) was found between the net counts and the optimal order of the PO-R Metz filter. At the count levels of clinical studies the PO-R Metz filter was found to control noise much more effectively and enhance the contrast when compared to the routinely used Hann filter alone, and produced images of better quality.

Biophysical Phenomena↗
PubMed1997

Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein.

We used [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and PET to study regional cerebral glucose utilization in seven patients with fatal familial insomnia (FFI), an inherited prion disease with a mutation at codon 178 of the prion protein gene. Four patients were methionine/methionine homozygotes at codon 129 (symptom duration, 8.5 +/- 1 months) and three were methionine/valine (MET/VAL129) heterozygotes (symptom duration, 35 +/- 11 months). A severely reduced glucose utilization of the thalamus and a mild hypometabolism of the cingulate cortex were found in all FFI patients. In six subjects the brain hypometabolism also affected the basal and lateral frontal cortex, the caudate nucleus, and the middle and inferior temporal cortex. Comparison between homozygous or heterozygous patients at codon 129 showed that the hypometabolism was more widespread in the MET/VAL129 group, which had a significantly longer symptom duration at the time of [18F] FDG PET study. Comparison between neuropathologic and [18F] FDG PET findings in six patients showed that areas with neuronal loss were also hypometabolic. However, cerebral hypometabolism was more widespread than the histopathologic changes and significantly correlated with the presence of protease-resistant prion protein (PrPres). Our findings indicate that hypometabolism of the thalamus and cingulate cortex is the hallmark of FFI, while the involvement of other brain regions depends on the duration of symptoms and some unknown factors specific to each patient. The present data also support the notion that PrPres formation is the cause of neuronal dysfunction in prion diseases.

Adult↗
PubMed1997

A method for assessing catheter patency in implanted pumps for long-term intraperitoneal insulin delivery.

Catheter complications are a common problem during long-term insulin therapy with implanted pumps. The purpose of this study was to test the feasibility of imaging intraperitoneal catheters with technetium (Tc) 99m in implantable devices for insulin delivery. Testing physical stability of an insulin/Tc 99 mixture did not show formation of insulin aggregates during a period up to 48 h on a rotating wheel. Five hundred microCurie (equal to 18 MBq) of Tc 99m were injected in the flush port of a pump for intraperitoneal insulin delivery implanted in patients with type I (insulin dependent) diabetes mellitus, and gamma camera images were obtained for 30 min. In patent catheters the tracer rapidly imaged the whole length of the catheter while in occluded catheters the tracer remained in the flush port, imaging only the portion of the catheter before the occlusion. In patent catheters in which insulin absorption was impaired, the tracer rapidly imaged the whole length of the catheter, but its removal from the peritoneum was delayed. Tc 99m imaging of intraperitoneal catheters for insulin delivery can be used to assess catheter patency and impaired delivery into the peritoneal cavity.

Catheterization↗
PubMed1997

Abnormal myocardial glucose handling in patients with syndrome X: effect of beta-adrenergic blockade.

The present study was designed to test the hypothesis that patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X), may exhibit abnormal myocardial glucose handling, as assessed by fluorodeoxyglucose (FDG) and positron emission tomography (PET) and to investigate the possibility that this abnormality could be reversed by treatment with betablockers, the drugs of choice in most patients with syndrome X. Eight consecutive patients (4 females, age 53 +/- 4 yrs) with syndrome X were studied. Off therapy, they underwent stress/rest 99m-TcMIBI SPET (360 degrees) and assessment of resting glucose metabolism by PET. PET studies were again performed after a 10 day treatment period on oral atenolol (100 mg/o.d.). All patients exhibited significant fasting FDG uptake in 2 or more myocardial regions. Overall, there were 28 of 48 segments (58%) with abnormal tracer uptake. On atenolol, there were only 5 segments with persistent FDG uptake (10%) in 2 patients. At rest, 7 patients exhibited perfusion defects in 14 myocardial segments. With stress performed in pharmacological wash-out, 5 patients developed perfusion defects in 10 myocardial segments. Eight of these segments were already underperfused at rest, and showed further reduction in perfusion after stress. All hypoperfused segments showed abnormal FDG uptake when the PET study was performed off therapy. The results suggest that, in patients with syndrome X, imbalance of the demand/supply ratio, either caused by limited coronary flow reserve or by primary vasoconstriction with reduction in myocardial perfusion, may determine a sustained metabolic shift towards anaerobic glycolysis. The mechanism by which atenolol improves metabolism in these patients could be simply related to reduction in O2 consumption.

Adrenergic beta-Antagonists↗