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J L Moretti

Publications and source records attributed to J L Moretti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Involvement of glutathione in loss of technetium-99m-MIBI accumulation related to membrane MDR protein expression in tumor cells.

UNLABELLED: It was reported recently that 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) uptake is drastically reduced in cancer cells that express the multidrug resistance (MDR) product, Pgp 170 kDa (Pgp), suggesting that 99mTc-MIBI is a transport substrate for this transmembrane glycoprotein. In our study, we explored if another pump, a multidrug resistance-associated protein (MRP), could affect 99mTc-MIBI uptake. In addition, we studied the involvement of intracellular glutathione (GSH) as a modulator of 99mTc-MIBI uptake by both Pgp and MRP proteins. METHODS: MDR1 and MRP gene expression in seven human tumor cell lines was determined on a transcriptional level by reverse transcriptase polymerase chain reaction and on a protein level using immunocytochemistry. Technetium-99m-MIBI uptake was quantified by measuring radioactivity retained in the cells incubated at 37 degrees C in the presence or absence of buthionine sulfoximine (BSO), which depletes cellular GSH. The cellular GSH content was determined with Ellman's reagent. RESULTS: Cell lines were classified according to their phenotypic characteristics: 1/MRP-/Pgp-: breast cancer cells (MCF7), lung carcinoma cells (H69S) and mouth epidermoid tumor cells (KB 3.1), 2/MRP-/Pgp+: MCF7 mdr+, KBA.1; and 3/MRP+/Pgp-: small-cell lung carcinoma (H69 AR and A 549). Technetium-99m-MIBI uptake was significantly lower in cells expressing MRP as well as Pgp compared to MRP/Pgp cells. Depletion of GSH by BSO resulted in an increase of 99mTc-MIBI uptake in multidrug resistant cells overexpressing MRP but not expressing Pgp. CONCLUSION: Technetium-99m-MIBI is extruded by both Pgp and MRP efflux pumps. However, MRP action is indirect and involves intracellular GSH for a presumed interaction with the 99mTc-MIBI before its effLux. Technetium-99m-MIBI seems to be a good candidate for a noninvasive marker to diagnose MDR1 related to Pgp and MRP expression in tumors of different origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Mechanism involved in gallium-67 (Ga-67) uptake by human lymphoid cell lines.

The gallium-67 (Ga-67) is a radionuclide used for diagnostic imaging. It is known for its ability to accumulate in inflammatory lesions and tumors, especially in lymphomas. The intracellular distribution and the uptake mechanism of Ga-67 remains a subject of discussion. In this work, we studied the mechanism of Ga-67 uptake in 4 human lymphoid cell lines: 38658, Jurkat, DG75 and U715. Our results have pointed out the heterogeneity of Ga-67 uptake among these cell lines. Using flow cytometry analysis, we reported the expression of transferrin-receptor (TfR) in each lymphoid cell line, and found a positive correlation between TfR density and the Ga-67 uptake (r = 0.99) in lymphoid cells. The anti-TfR monoclonal antibody (MoAb) blocked significantly the Ga-67 uptake in all lymphoid cell lines indicating the Ga-67 uptake as a TfR-dependent mechanism. This mechanism has been saturated with different cold gallium concentrations. A total inhibition of Ga-67 uptake was obtained at a 10(-4) M cold gallium concentration. To conclude, we have shown that the Ga-67 uptake is TfR-dependent in lymphoid cells. Thus, the gallium penetrates in lymphoid cells by an active mechanism which can be saturated.

Antibodies, Monoclonal↗
PubMed1997

[Pulmonary doppler. Early results in normal pregnancies].

OBJECTIVE: The study of fetal lung circulation by means of pulmonary Doppler investigation. METHODS: Pulmonary Doppler ultrasound obtained with color pulsed-Doppler with a 3.5-5 Mhz probe. Measure of resistance index and pulsatility index. PATIENTS: Forty seven pregnant women with singleton, between 18 and 39.5 weeks gestation, were recruited to have a pulmonary Doppler ultrasound. 7 fetuses had intra uterine fetal growth retardation (IUGR). Overall, 50 Doppler velocity waveforms were measured. RESULTS: Resistance and pulsatility index were measured in all patients and at each examination. Resistance index (0.86 +/- 0.03) and pulsatility index (2.46 +/- 0.34) were found to be stable during pregnancy. Pulmonary pulsatility index in IUGR fetuses (2.71 +/- 0.33) were found to be higher than those in normotrophic infants (p = 0.006), whereas no difference was found in resistance index between the same subgroups. Moreover, no difference was found in pulsatility index measurements between preterm small-for-gestational age fetuses and normotrophic fetuses measured between 36 and 39.5 weeks gestation (2.68 +/- 0.31 vs 2.49 +/- 0.28). CONCLUSION: Pulmonary resistance index is not statistically different between nomotrophic and IUGR fetuses. In contrast pulmonary pulsatility index is significantly higher in IUGR fetuses when compared with normotrophic fetuses. Pulmonary Doppler ultrasound should be evaluated in a larger trial and correlation between Doppler measurements and fetal lung maturation should be studied.

Case-Control Studies↗
PubMed1996

Primary breast cancer imaging with technetium-99m sestamibi and its relation with P-glycoprotein overexpression.

The aim of this preliminary study was to evaluate retrospectively sestamibi scintigraphy in relation to the presence of the 170-kDa P-glycoprotein (Pgp), which represents an expression of multidrug resistance in patients with primary breast cancer. Fifteen women (age range 37-76 years) were referred for technetium-99m sestamibi scintigraphy because of suspicious breast lesions detected by mammography and ultrasonography, and subsequently assessed by fine-needle aspiration. Scintigraphy was performed 30 min following the injection of 500 MBq 99mTc-sestamibi. Three planar anterior and oblique images were obtained with the patient in the supine position. Excised tumours were assessed for cytosolic CA 15.3, oestrogen (OR) and progesterone (PR) receptors and c-erb B2 neu oncogene. Pathology revealed that only 13 of the 15 patients had malignant tumours. The two benign tumours were sestamibi-negative and Pgp-positive. Sestamibi scintigraphy was positive in 10 of the 13 malignant lesions (including nine of ten infiltrating ductal carcinomas). Two of the three lesions with false-negative scintigraphy were Pgp-negative; in one of these cases histology revealed an invasive lobular carcinoma and in the other, mucinous adenocarcinoma. The third false-negative lesion was a Pgp-positive infiltrating ductal carcinoma which was c-erb B2 neu-negative but CA 15.3-, OR- and PR-positive. This preliminary study confirms that the resistance to chemotherapy which may occur in patients with primary breast cancer can be a cause of negative sestamibi scintigraphy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Somatostatin receptor imaging in small cell lung cancer.

To determine its usefulness, we evaluated 111In-DTPA-Octreotide (octreotide scintigraphy) in the initial staging of 19 patients with histologically proven small cell lung cancer (SCLC) and compared the results to those of conventional imaging. Images performed during initial staging demonstrated 21 known pulmonary lesions and two known supraclavicular nodes. We detected a previously unknown mediastinal lesion. The number of metastases was underestimated, with no liver (5), brain (1) or skin metastases detected. Bone lesions were identified in 4 out of 5 patients. There were fewer lesions detected with octreotide scintigraphy than with bone scintigraphy (except for one case). We therefore conclude that octreotide scintigraphy is a highly effective method for detecting SCLC primary tumour and supraclavicular nodes; the procedure is of limited value for distant metastasis. Further studies are needed to establish its ability for detecting residual intrathoracic disease, and confirm the value of octreotide scintigraphy in differentiating residual disease from other benign lesions.

Adult↗
PubMed1996

Technetium-99m-sestamibi uptake by human benign and malignant breast tumor cells: correlation with mdr gene expression.

UNLABELLED: Early diagnosis of multidrug-resistance (MDR) development is extremely important for the judicious choice of treatment protocols in breast cancer chemotherapy. In this study, the mechanism of 99mTc-sestamibi uptake by nine human breast tumor cell lines was analyzed as a function of P-glycoprotein (PgP) expression. METHODS: Technetium-99m-sestamibi radioactivity incorporation into the cells was determined after different times of incubation at 37 degrees C. We analyzed the mechanism of 99mTc-sestamibi uptake as follows: (a) effect of temperature (4 degrees C); (b) influence of extracellular 99mTc-sestamibi concentration; and (c) competitive inhibition of cell uptake with cold 99mTc-sestamibi. Technetium-99m-sestamibi uptake was compared to the level of PgP determined by Western blotting. The PgP reversing effect of verapamil was evaluated at different drug concentrations (50, 200, 500 microM). RESULTS: Technetium-99m-sestamibi uptake plateaued at 60 min, which was 14 times lower at 4 degrees C than at 37 degrees C and was directly proportional to the extracellular concentration between 0.3 and 10 nM. Technetium-99m-sestamibi percentage uptake by cells expressing nonimmunodetectable levels of PgP was significantly higher (7.3% +/- 0.6% (s.d.) to 14.9% +/- 1.9%) than that by cells expressing high PgP levels (0.7% +/- 0.4%, p < 0.001). In the presence of verapamil, a known reverser of PgP functions, 99mTc-sestamibi uptake was increased by a factor of 2 in cells expressing no detectable levels of PgP and by a factor of 12 in cells with high PgP levels. CONCLUSION: Technetium-99m-sestamibi uptake by these breast tumor cells is energy-dependent but not specific. These data suggest that 99mTc-sestamibi imaging may be used as a noninvasive technique to diagnose the presence of MDR in breast tumors in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octreotide: can we predict the response to chemotherapy in small cell lung cancer?

A case of small cell lung carcinoma (SCLC) demonstrating uptake on functional indium-111 octreotide scintigraphy is presented. Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy clearly delineated an absence of radionuclide uptake at the tumour site. This suggested the presence of multidrug resistance-mediated P glycoprotein (Pgp) on tumour cells, which recognizes certain chemotherapeutic agents as well as MIBI as a substrate and avoids radionuclide concentration. Following three courses of chemotherapy, the patient failed to improve and eventually died. This case demonstrates the importance of functional images, which have the potential to predict the outcome in response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Plasma kinetics of 125I-labelled amyloid P component in beta 2M amyloidosis: a possible approach to quantitate disease activity.

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P < 0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.

Adult↗
PubMed1994

Dual-isotope myocardial imaging: feasibility, advantages and limitations. Preliminary report on 231 consecutive patients.

Two hundred and thirty-one patients underwent dual-isotope myocardial imaging (rest thallium-201 followed by stress technetium-99m sestamibi). The feasibility of the procedure was excellent: camera scheduling flexibility was improved and the duration of the procedure was less than that of a classical stress-redistribution procedure. Interpretation of defects due to image attenuation was facilitated by the different attenuation properties of 201Tl and 99mTc-sestamibi in 11 of 19 patients. 201Tl cross-over on 99mTc was found to be 15% +/- 3% with doses of 201Tl and 99mTc-sestamibi of 3 and 10 mCi, respectively, and 7% +/- 2% with doses of 3 and 20 mCi. This protocol should preferentially be reserved for patients with a history of myocardial infarction and/or a basal left ventricular dysfunction, in whom assessment of myocardial viability is of major interest. Extensive clinical validation of the dual-isotope procedure is required and optimal acquisition and reconstruction parameters should be established.

Adult↗
PubMed1994

Non-matched images with 123I-IMP and 99mTc-bicisate single-photon emission tomography in the demonstration of focal hyperaemia during the subacute phase of an ischaemic stroke.

Focal hyperaemia is a fairly common phenomenon in the subacute phase of an ischaemic stroke. This has rarely been reported with iodine-123 iodoamphetamine (IMP) and has never been identified using technetium-99m bicisate (99mTc-ECD). In this report, we present the case of a patient suffering from a left cerebral posterior stroke. 123I-IMP single-photon emission tomography (SPET) images showed a large area of significantly increased IMP activity located in the left occipital region whereas 99mTc-bicisate SPET displayed hypoactivity in the same area.

Amphetamines↗