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J L Moretti

Publications and source records attributed to J L Moretti.

At least 19 recordsLinked to original sources
PubMed2005

Cerebrospinal fluid MR dynamics and risk of falls in the elderly.

RATIONALE AND OBJECTIVES: To investigate the relationship between CSF dynamics and risk of falls of unknown origin in the elderly. POPULATION AND METHODS: Phase contrast MR studies allowed CSF aqueductal flow quantification on 23 community-dwelling older people initially explored for mild cognitive impairment. Mobility assessment included report of falls, talking walking test, stance test, one leg standing test, up and go test, and measurement of fast gait speed. RESULTS: History of falls was associated with larger aqueduct, steeper diastolic slopes higher ratios RDV/SD of diastolic volume/CSF systole duration (p</=0.0006). Amplitude CSF parameters, diastolic slopes and RDV/SD appeared correlated with the aqueduct area (p<0.01). CONCLUSIONS: These preliminary data suggest that disturbances of CSF dynamics could play a role in mobility decline with aging especially in falls of unknown origin.

Accidental Falls↗
PubMed2004

Spontaneous mitochondrial membrane potential change during apoptotic induction by quercetin in K562 and K562/adr cells.

Natural products from plants such as flavonoids are potential drugs to overcome multidrug resistance (MDR) in cancer treatments. However, their modes of action are still unclear. In this study, the effects of quercetin on mitochondrial membrane potential (DeltaPsim) change as well as quercetin's ability to induce apoptosis and inhibit Pgp-mediated efflux of 99mTc-MIBI in K562/adr cells were investigated. Quercetin exhibits cytotoxicity against erythroleukemic cells: IC50 are 11.0 +/- 2.0 micromol/L and 5.0 +/- 0.4 micromol/L for K562 and K562/adr, respectively. Quercetin induces cell death via apoptosis in both K562 and K562/adr cells and does not inhibit Pgp-mediated efflux of 99mTc-MIBI. Quercetin (10 micromol/L, 3 h) and etoposide (100 micromol/L, 24 h) induce similar levels of apoptosis in K562 and K562/adr cells. Quercetin induces an increase followed by a decrease in |DeltaPsim| value depending on its concentration. A decrease in the |DeltaPsim| value is associated with an increase in the percentage of early apoptotic cells. It is clearly shown that quercetin results in a spontaneous DeltaPsim change during apoptotic induction. Therefore, quercetin is potentially an apoptotic-inducing agent, which reacts at the mitochondrial level.

Annexins↗
PubMed2003

Calcitonin precursor levels in human medullary thyroid carcinoma.

DESIGN: The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients. METHODS: Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1. RESULTS: All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly. CONCLUSION: This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.

Biomarkers, Tumor↗
PubMed2001

The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response.

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq 99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and 99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of 99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33% +/- 9% vs 17% +/- 9%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of 99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Could 99mTc-MIBI be used to visualize the apoptotic MCF7 human breast cancer cells?

Defects in key components of apoptotic pathways provide a survival advantage to cells and have been implicated as important factors in tumorogenesis. As therapeutic drug-induced apoptosis is a key component in treatment of most cancers, alterations in apoptotic pathways may be critical to drug resistance. The question is: would it be possible to distinguish apoptotic cells and resistant cells with a same radiotracer? In this study, we investigated the ability of sodium phenylacetate (NaPa), a natural cytostatic proapoptotic metabolite, to induce apoptosis in MCF7 human breast cancer cells. Then, we tested the 99mTc-MIBI accumulation in these apoptotic cells. Annexin V-FITC was used to identify apoptotic cells by flow cytometry. Ours results demonstrated that a 72 hr treatment of MCF7 cells with 40 mM NaPa induced apoptosis in 60% of cells. In a parallel way, 99mTc-MIBI accumulation in NaPa treated cells decreased for concentrations higher than 20 mM NaPa. Thus, 99mTc-MIBI accumulation decreased correlatively with the increasing percentage of apoptotic cells obtained by treatment of MCF7 cells with NaPa. These data demonstrate that NaPa induced apoptosis in MCF7 cells and that 99mTc-MIBI is a negative tracer of apoptosis: the more MCF7 cells were engaged in the apoptotic pathway, the more 99mTc-MIBI accumulation decreased in these MCF7 apoptotic cells.

Apoptosis↗
PubMed2000

Improving the measurement of the 99Tc(m)-ECD brain perfusion index by temporal analysis.

Matsuda et al. have described a non-invasive method for brain perfusion quantification by computing the ratio of the cumulated counts in the cerebral hemispheres and aortic arch. The regions of interest (ROIs) are drawn manually and are observer dependent. The aim of this study was to develop a new method designed to minimize the intra- and interobserver variability when drawing the different ROIs. A dynamic study was performed as in Matsuda's method on 30 patients using technetium-99m ethyl cysteinate dimer (99Tc(m)-ECD) (ID: 800 MBq+/-33 MBq). The manual method of drawing ROIs was then compared with the following, automated one. A temporal analysis was performed on the cardiac first-pass study to obtain parametric images of the thorax. An ROI of the aortic arch was drawn automatically by means of an isocontour algorithm on the resulting views. The whole sequence was reframed and filtered by a temporal low-pass filter. Hemispheric brain ROIs were delineated on a summed image. Matsuda's algorithm was then applied. Intraobserver variability was evaluated for the classical Matsuda method. The correlation in brain perfusion index (BPI) measurements was r = 0.8976 for naive observers and r = 0.9443 for well-trained observers. Interobserver variability was also evaluated; the correlation was r = 0.7574 for naive observers and r = 0.9190 for well-trained observers. With our proposed method, the correlation in the measurements of BPI for evaluating the intraobserver variability was r = 0.9955 for naive observers and r = 0.9989 for well-trained observers. For interobserver variability, the results were r = 0.9234 for naive observers and r = 0.9230 for well-trained observers. We conclude that temporal analysis allows brain perfusion to be measured in a semi-automatic manner, and improves the reproducibility compared with the original method of Matsuda, particularly for naive observers.

Adult↗
PubMed2000

Assessment of malignancy in pulmonary lesions: FDG dual-head coincidence gamma camera imaging in association with serum tumor marker measurement.

UNLABELLED: The purpose of the study was to evaluate the performance of dual-head coincidence gamma camera imaging using FDG in association with serum marker assays in identifying lung carcinoma in patients with abnormal findings on chest radiography. METHODS: A prospective evaluation of FDG imaging with coincidence detection emission tomography (CDET) using a dual-head gamma camera combined with the assessment of 3 sensitive serum markers of lung cancer (carcinoembryonic antigen, neuron specific enolase, and CYFRA 21-1) was performed on the same day on 58 consecutive patients with known or suspected lung malignancy. RESULTS: Fifty-three patients were proven to have lung cancer, and 5 patients had benign lung disease. Coincidence imaging showed significantly increased FDG uptake in 49 of 53 patients with proven malignancy (sensitivity, 92.5%) and in 3 patients with benign disease. FDG imaging had negative findings in 4 patients with proven malignancy and 2 patients with benign disease. Serum tumor marker levels were elevated in 42 of 53 cancer patients (sensitivity, 79.2%) and normal in 11 patients with proven malignancy. Nine patients with proven malignancy had positive findings on FDG images and negative marker assays. Two patients with proven malignancy had negative findings on FDG images and positive marker assays. The positive predictive value for lung cancer was 94.2% for FDG alone and 97.6% for FDG in association with serum markers. CONCLUSION: In this study, FDG CDET imaging was a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels was less accurate than FDG imaging, positive FDG results found in association with positive markers significantly increased the likelihood of lung malignancy.

Adult↗
PubMed2000

111In-pentetreotide scintigraphy in patients with Langerhans' cell histiocytosis.

UNLABELLED: Langerhans' cell histiocytosis is a granulomatous disease that may involve multiple organs and the prognosis of which is highly variable. Because the prognosis depends particularly on the number of tissues involved, the accurate identification of the organs involved by granulomatous lesions is of critical importance. We hypothesized that 111In-pentetreotide scintigraphy would be useful for evaluation of patients with Langerhans' cells histiocytosis. METHODS: Thirteen patients (38.3+/-10.4 y) with Langerhans' cell histiocytosis (8 patients with unifocal lung disease, 5 with multifocal disease) received intravenous 111In-pentetreotide (111-222 MBq), and planar images were obtained at 24 h after injection. Pulmonary uptake was quantified using a lung-to-background ratio (L/B) and compared with a population of 10 normal scintigrams. For the other sites, uptake of radioactivity in disease-related areas was visually assessed. RESULTS: Ten of 12 patients with lung involvement had increased lung uptake (UB, 2.23+/-0.49 versus 1.34+/-0.07; P < 0.001). In the patients with multifocal disease, increased 111In-pentetreotide uptake was found in disease-related areas such as the salivary glands, the skin, the soft tissues, and the bones. However, somatostatin receptor imaging was insensitive for detecting central nervous system and liver involvement and most skin lesions. CONCLUSION: 111In-pentetreotide imaging may be useful in Langerhans' cell histiocytosis. Further study will indicate whether 111In-pentetreotide is a relevant tracer in the management of histiocytosis.

Adult↗
PubMed1999

Uptake of liposome-encapsulated 99Tcm-MIBI by sensitive and multidrug-resistant tumour cell lines.

It is well established that accumulation of 99Tcm-sestamibi (99Tcm-MIBI) is much higher in sensitive than multidrug-resistant tumour cells expressing the permeability glycoprotein 170 (Pgp 170) as well as a multidrug-resistance related protein (MRP). Thus 99Tcm-MIBI is a good candidate for diagnosing the multidrug-resistance phenotype by in vivo imaging. However, the blood clearance of 99Tcm-MIBI is too rapid to achieve optimal accumulation in tumours and uptake in the liver, spleen, heart and muscle is too high for it to be an excellent in vivo tumour tracer. One way of prolonging the bioavailability of 99Tcm-MIBI is to use liposomes which do not affect its accumulation in tumour cells. We explored this possibility in vitro using two sensitive and five resistant cell lines, two of them expressing Pgp 170 and three others over-expressing MRP. 99Tcm-MIBI was incorporated into liposomes prepared by thin film hydration with phosphate-buffered saline using distearoyl phosphatidyl choline, distearoyl phosphatidyl ethanolamine and cholesterol in a ratio of 1.85:0.15:1.00. Liposome diameter was 97.9 +/- 4.5 nm as determined by dynamic light scattering. 99Tcm-MIBI uptake was quantified by measuring radioactivity retained in the cells incubated at 37 degrees C with liposome-encapsulated 99Tcm-MIBI or with free radiotracer in the presence of empty liposomes. In both experimental cases, 99Tcm-MIBI accumulation was similar to that obtained in the presence of free 99Tcm-MIBI only: it was much higher in sensitive than in resistant Pgp 170-positive and MRP-positive cells. Encapsulation in liposomes does not alter the potency of 99Tcm-MIBI to distinguish the sensitive and resistant tumour cells. Our results suggest that future studies should assess the usefulness of the encapsulated form of 99Tcm-MIBI for in vivo imaging of tumours.

Adenocarcinoma↗
PubMed1999

Metoclopramide has no effect on abdominal activity of sestamibi in myocardial SPET.

It has been suggested that metoclopramide may reduce artefacts caused by intestinal activity super-imposed on myocardial uptake of MIBI SPET. This study compared the abdominal activity of MIBI in patients given metoclopramide versus a control group. Forty-seven patients with normal scintigrams or with completely normal inferior wall perfusion underwent rest 201T1 + stress MIBI testing. Twenty-four patients arbitrarily received 10 mg metoclopramide orally 45 min before the MIBI injection and 23 patients no metoclopramide. The patients were divided according to the stress performed: 23 patients had exercise and 24 patients dipyridamole infusion, and a comparison was done between patients with metoclopramide and those without. Myocardial and abdominal activity were assessed at 15 and 60 min on three separate projections and the mean myocardium-to-abdomen ratios were computed. The ratio was 1.30 +/- 0.19 and 1.57 +/- 0.23 in the patients with exercise and metoclopramide versus 1.36 +/- 0.18 and 1.64 +/- 0.23 in the patients with exercise alone at 15 and 60 min respectively. The ratio was 0.92 +/- 0.13 and 1.21 +/- 0.21 in the patients with dipyridamole infusion and metoclopramide versus 1.02 +/- 0.17 and 1.33 +/- 0.16 in the patients with dipyridamole alone at 15 and 60 min respectively. These differences were not statistically significant. In conclusion, metoclopramide has no effect on MIBI abdominal activity and is not recommended in routine practice.

Abdomen↗
PubMed1999

The role of 99Tcm-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: comparison with 131I-MIBG and 99Tcm-MDP scintigraphy.

In this study, we investigated prospectively the diagnostic role of 99Tcm-MIBI for staging and for predicting the therapeutic response of stage IV neuroblastoma compared with 131I-MIBG imaging and 99Tcm-MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with 99Tcm-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg-1 99Tcm-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with 131I-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by 131I-MIBG scintigraphy. None of the primary lesions demonstrated significant 99Tcm-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 131I-MIBI-avid neuroblastoma metastases that were 99Tcm-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were 99Tcm-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for 131I-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate 99Tcm-MIBI. Clinical evaluation of patients with no 99Tcm-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. All 99Tcm-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that 99Tcm-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy.

3-Iodobenzylguanidine↗
PubMed1999

Central nervous system involvement in Sjögren's syndrome: evidence from neuropsychological testing and HMPAO-SPECT.

OBJECTIVE: To investigate the clinical, neuropsychological and imaging manifestations of Sjögren's syndrome (SS), a chronic auto-immune disease with peripheral and central nervous system (CNS) involvement. DESIGN/METHODS: Fourteen female patients suffering from confirmed SS underwent within 2 weeks: neurological examination, immunological staging, brain MRI, brain 99m Tc-HMPAO SPECT, psychological evaluation and in-depth neuropsychological testing. RESULTS: All patients showed neuropsychological abnormalities. The cognitive symptoms were of the same type in all patients, mostly frontal lobe syndrome and memory problems. The neuropsychological involvement was not associated with other kinds of CNS involvement or MRI abnormalities, but accurately reflected HMPAO imaging results. CONCLUSIONS: The results of this study indicate that cognitive evaluation is the most sensitive clinical test to diagnose CNS involvement in patients with SS, and that CNS involvement in SS seems to be more frequent when systematically assessed by neuropsychological tests.

Adult↗
PubMed1999

67Ga scintigraphy in B-cell non-Hodgkin's lymphoma: correlation of 67Ga uptake with histology and transferrin receptor expression.

UNLABELLED: 67Ga scintigraphy is routinely used in the management of non-Hodgkin's lymphomas (NHLs), but the heterogeneity of 67Ga uptake in the different NHL histological subtypes has not been clearly explained. The transferrin receptors (TfR/CD71) play an important role in the mechanisms of 67Ga uptake by tumor cells. However, the relationship between the 67Ga uptake in NHL and the TfR/CD71 expression in lymphomatous cells remains to be defined. The aim of this study was to determine the intensity of 67Ga uptake in different histological subtypes of B-cell NHL (B-NHL) and to compare this uptake with the expression of TfR/CD71 on lymphomatous cells. METHODS: 67Ga scintigraphy of 47 patients having histologically proven lymphomas was investigated. 67Ga uptake was semiquantitatively evaluated in regions of interest and was reported as 67Ga uptake index (GaUI). In all cases, biopsies were reviewed for classification of NHL. The expression of TfR/CD71 was determined on frozen sections and was semiquantitatively evaluated. The relationships between GaUI, histology and TfR/CD71 were investigated. RESULTS: The values of GaUI were significantly related to the different histological subtypes analyzed (P = 0.0007) and to the presence of a large cells component, thus demonstrating that 67Ga uptake rose with the grade of lymphoma. Moreover, the values of GaUI and TfR/CD71 were closely related in the tested cases (P = 0.0059). CONCLUSION: There were three factors influencing 67Ga uptake in NHL: histology, TfR/CD71 expression and the presence of a large cells component. This justifies the usefulness of 67Ga scintigraphy in staging the TfR/CD71-positive lymphomas.

Adolescent↗
PubMed1998

Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P-glycoprotein-mediated and multidrug-resistance protein-associated multidrug-resistance phenotypes.

The overexpression of two membrane glycoproteins, P-glycoprotein and multidrug-resistance protein (MRP1) is a major cause of resistance to chemotherapeutic agents in the treatment of human cancers. Both proteins confer a similar multidrug-resistant (MDR) phenotype. 99mTc-MIBI, a myocardial imaging agent, which is also useful for the detection of a variety of tumours, has been shown to be a substrate for P-glycoprotein and MRP1. It thus may provide additional information about the P-glycoprotein and MRP1 status of tumour cells. In order to obtain information on the substrate specificity of these proteins, we have studied the transport kinetics of Tc-MIBI in two cell lines, K562/ADR and GLC4/ADR, which overexpress P-glycoprotein and MRP1, respectively. The mean active efflux coefficient ka, which is proportional to the ratio of maximal efflux rate VM to the apparent Michaelis-Menten constant Km, used to characterise the efficiency of the active efflux, was very similar being 1.9 +/- 0.6 x 10(-11) s(-1) x cells x ml and 1.3 +/- 0.5 x 10(-11) s(-1) x cells x ml for drug-resistant K562 and GLC4, respectively. These values are 50-100-times lower than for daunorubicin and other anthracycline derivatives, strongly suggesting that the efficiency of both transporters to pump Tc-MIBI is by far less than that to efflux anthracyclines. Our data show that (a) P-glycoprotein and MRP transporter efficiencies to wash out Tc-MIBI are similar, in spite of a different suspected mechanism of its transport and (b) that both transporters are less efficient to pump Tc-MIBI than to pump anthracyclines (the ka parameter is about 100-times lower for TC-MIBI than for anthracycline).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Enalapril plus frusemide MAG3 scintigraphy in hypertensive patients with atherosclerosis and moderate renal insufficiency.

We performed a retrospective study on 26 patients with moderate renal failure (mean GFR = 51 +/- 21 ml min-1 1.73 m-2), hypertension and atherosclerosis. Apart from three patients who had completely normal renal Doppler ultrasonography, all patients underwent renal angiography. Three groups of kidneys with different atherosclerotic renal artery involvement were identified: Group 1, 24 kidneys with no renal artery stenosis (RAS); Group 2, 18 kidneys with mild (> 25% and < 50% diameter) RAS; and Group 3, 10 kidneys with moderate (> 50% diameter) RAS. We used a two-day protocol with frusemide plus enalapril 99Tcm-MAG3 scintigraphy. The mean parenchymal transit time (MPTT), time to the maximum activity (time to peak) of the renal curve (Tmax), residual activity and split renal uptake were evaluated. The measured parameters did not differ before and after enalapril in Group 1 or in Group 2. In Group 3, MPTT and residual activity differed significantly (P < 0.025) before and after enalapril. The Tmax before and after enalapril, MPTT before and after enalapril and residual activity after enalapril differed significantly (P < 0.05) between Groups 1 and 3 and between Groups 2 and 3. Threshold values were obtained to maximize diagnostic accuracy. The Tmax, MPTT and residual activity after enalapril gave satisfactory results, and MPTT performed best with a 75% positive predictive value and a 98% negative predictive value for the diagnosis of renal artery stenosis. We conclude that MPTT, measured after enalapril administration, is a useful parameter to detect renal artery stenosis in patients with hypertension, atherosclerosis and moderate renal insufficiency.

Adult↗