[Nuclear medicine in oncology: new diagnostic and therapeutic methods].
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Carcinoma, Hepatocellular↗
Biomedical subjects
J Maublant
Publications and source records attributed to J Maublant.
[Nuclear oncology update].
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Bone Neoplasms↗
Comparative 99mTc-sestamibi and 3H-daunomycin uptake in human carcinoma cells: relation to the MDR phenotype and effects of reversing agents.
UNLABELLED: Because 99mTc-sestamibi (MIBI) appears to be a potent candidate for multidrug resistance (MDR) evaluation in tumors, its cellular uptake should be similar to that of 3H-daunomycin in a variety of conditions of expression and inhibition of MDR activity. METHODS: We used a human rhinopharyngeal carcinoma cell line (KB-3-1) and its MDR variant (KB-A1). Cells were incubated 2 h with 99mTc-MIBI and 3H-daunomycin under control conditions or in the presence of a reversing agent such as verapamil (10 pmol/L), PSC833 (1 micromol/L) or S9788 (5 micromol/L). RESULTS: Relative to the KB-3-1-sensitive cells, accumulations of 99mTc-MIBI and 3H-daunomycin were reduced to 31% +/- 5% and 36% +/- 11% (P < 0.001 for both) in KB-A1-resistant cells. In sensitive cells, accumulation of both agents was increased by verapamil and PSC833 (range 115%-140%; P < 0.05) but not by S9788. In KB-A1 cells, only S9788 significantly increased the cellular uptake of 99mTc-MIBI (138% +/- 25%; P < 0.01), whereas the intracellular uptake of 3H-daunomycin was markedly increased with the three reversing agents (up to 311% +/- 37% with S9788; P < 0.001). With this last treatment, uptake of 3H-daunomycin in KB-A1 cells nearly returned to its basal level in sensitive cells. CONCLUSION: 99mTc-MIBI monitors the MDR phenotype of tumor cells effectively but responds to reversing agents differently than 3H-daunomycin.
Antibiotics, Antineoplastic↗
Scintimammography with technetium-99m methoxyisobutylisonitrile: results of a prospective European multicentre trial.
The aim of the trial was to determine the diagnostic accuracy of scintimmammography with technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) in the detection of primary breast cancer and to verify its clinical usefulness. A total of 246 patients with a suspicious breast mass or positive mammogram were included in this prospective European multicentre trial. At 5 min and 60 min (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min p.i. one anterior image was acquired for 10 min. There were 253 lesions (195 palpable and 58 non-palpable), in respect of which histology revealed 165 cancers and 88 benign lesions. Institutional and blinded read results were correlated to core laboratory histopathology results obtained during excisional biopsy. Diagnostic accuracy for the detection of breast cancer was calculated per lesion. The overall sensitivity and specificity of blinded read scintimammography were 71% and 69%, respectively. For palpable lesions, the sensitivity of blinded read and institutional read scintimammography was 83% and 91%, respectively. Sensitivity was not dependent on the density of the breast tissue. Invasive ductal and invasive lobular cancers showed similar sensitivity. The sensitivity and specificity of mammography were 91% and 42%, respectively, and did not depend on the tumour size. In 60% of false-negative mammograms, 99mTc-MIBI was able to diagnose malignancy (true-positive). High-quality imaging with 99mTc-MIBI has a high diagnostic accuracy for the detection of primary breast cancer. Used as a complementary method, scintimammography with 99mTc-MIBI can help to diagnose breast cancer at an earlier stage in patients with dense breasts.
Breast Neoplasms↗
Cultured neonatal rat cardiomyocytes and 99mTc-sestamibi to assess the direct effects of cardioplegia.
The efficacy of cardioplegia in neonatal myocardial protection is still a matter of debate. 99mTc-sestamibi cellular accumulation reflects sarcolemmal and mitochondrial electrical gradients. It was used to monitor the direct effects of two cardioplegic solutions, modified St Thomas' Hospital and Bretschneider, on normoxic and metabolically-inhibited cultured cells. Cellular accumulation of 99mTc-sestamibi, expressed by the ratio between intra and extra cellular concentrations, was assessed in three different sets of neonatal rat cardiomyocytes. Cells were either treated with different concentrations of modified St Thomas' solution (50, 75, 100%), they were treated or recovering from a treatment with modified St Thomas and Bretschneider solutions at 50% concentrations, or were recovering from treatment with modified St Thomas' and Bretschneider solution at 50% concentrations mixed with metabolic inhibitors. Cardioplegia depressed the tracer accumulation in a concentration-dependent manner. This effect was independent of the type of cardioplegia (120-min uptake, as a percentage of control values, modified St Thomas' 68+/-12 and Bretschneider 59+/-7) and was rapidly reversible. Cardioplegia was unable to prevent the depression of tracer accumulation induced by metabolic inhibitors and even induced a deleterious effect (120-min uptake, as a percentage of control values, metabolic inhibitors 69+/-12, metabolic inhibitors + modified St Thomas 38+/-14, metabolic inhibitors + Bretschneider 43+/-6) during recovery after 30 min of metabolic inhibition. It was concluded that cardioplegia has an apparent detrimental effect on neonatal cardiomyocytes accumulation of 99mTc-sestamibi during recovery from an ischaemic-like insult.
Animals↗
[Positron emission tomography (PET) and (F-18)-fluorodeoxyglucose in (FDG) in cancerology].
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a scintigraphic imaging technique undergoing a rapid growth in the field of oncology. The constant progress of the detectors, either CDET or PET dedicated cameras, allows to obtain in routine conditions images with a 5 mm spatial resolution. Absolute tracer uptake quantification is also possible, which allows to evaluate objectively therapy efficacy. The mechanisms of FDG tissular accumulation are now better understood. Increase of glycolysis and of transmembrane transport of glucose seems to be at the origin of the high tumorous accumulation of FDG. The main current oncologic application of FDG PET is the diagnosis of malignancy of the isolated pulmonary nodules, with a sensitivity of more than 95%, and in the staging of lung cancer where PET shows higher performances than conventional imaging. The same stands in cutaneous melanoma and for malignancies of the digestive tract, either in colorectal, pancreatic or esophageal localizations. In colorectal cancers, the role of PET has for long being recognized in the differential diagnosis between recurrence and postoperative fibrosis. In the head and neck tumors, FDG also allows to differentiate between recurrence and postradiation necrosis. In lymphoma, the most suitable site for biopsy can be identified on a PET scan and therapy efficacy can also be assessed. In breast cancer, the detection of metastases seems to be possible with FDG. In brain and thyroid cancers, the role of FDG PET remains to be further determined. The low uptake of FDG in prostate cancer metastasis is not in favor of its use in this indication. In conclusion, the indications of FDG PET in oncology are now becoming more precise and it can be expected that clinical PET centers will soon appear in France.
Digestive System Neoplasms↗
Scintigraphic imaging of breast tumors.
Technetium-99m-sestamibi scintigraphy has recently emerged as a new procedure for the imaging of malignant breast tumors. A large clinical experience has now been collected and this article reviews the main published results. The major drawback of the procedure appears to be its low sensitivity in detecting lesions smaller than 1 cm. The biological background underlying the tracer accumulation is also described. The stimulating potent applications of this functional imaging technique to non-invasively explore the development, and possibly the reversal, of a multidrug resistance under chemotherapy are discussed. The data related to the use of the positron emitter fluor-18-labeled fluorodeoxyglucose (FDG), a very promising agent for imaging breast as well as other solid tumors, are also reviewed. This situation of specific agents, still under development and such as labeled receptor ligands, is examined.
Breast Neoplasms↗
Validity of a model of cultured myocardial cells for assessment of cardioplegia.
Myocardial protection is usually studied in vitro on perfused heart preparations, but never directly on cultured cardiomyocytes. We evaluated a model of cultured newborn rat cardiomyocytes to study both the cytotoxicity and the protective effect against chemical hypoxia of three cardioplegic solutions (St Thomas' I, Bretschneider, St Thomas' II) under normothermic (37 degrees C) and hypothermic (4 degrees C) conditions. Cytotoxicity was evaluated in 50% and 100% concentrations of the cardioplegic solutions with incubation times from 90 to 360 min. Myocardial protection was studied in 50% cardioplegic solution with metabolic inhibitors. Immediate and late viabilities, after 24 h of recovery in the medium, were evaluated by simultaneous staining with fluorescein diacetate and propidium iodide. At 37 degrees C, the 50% concentration of the three cardioplegic solutions did not modify cell viability. At 37 degrees C, with 360 min of incubation, the 100% concentration of the St Thomas' I and Bretschneider solutions diminished immediate viability (mean +/- SD; medium 87% +/- 2%; St Thomas' I 58% +/- 5%; Bretschneider 37% +/- 8%; St Thomas' II 89% +/- 3%) as well as late viability (medium 69% +/- 2%; St Thomas' I 32% +/- 3%; Bretschneider 24% +/- 7%; St Thomas' II 65% +/- 4%). At 4 degrees C, immediate and late viabilities were unaffected by cardioplegic solutions. At 37 degrees C, after 360 min incubation time, metabolic inhibitors diminished immediate viability to 29% +/- 1% and late viability to zero. None of the three cardioplegic solutions used at 50% concentration prevented this effect. At 4 degrees C, immediate viability was not significantly affected by metabolic inhibitors (73% +/- 10%), but the use of Bretschneider cardioplegic solution seemed to be detrimental (53% +/- 9%). On the other hand, recovery phase after pretreatment with metabolic inhibitors with or without cardioplegic solutions for 360 min significantly diminished late viability (medium 63% +/- 7%; metabolic inhibitors 17% +/- 8%; St Thomas' I 17% +/- 6%; Bretschneider 8% +/- 6%; St Thomas' II 15% +/- 3%) and again cardioplegia was inefficient. In conclusion, in this in vitro model for the study of cardioplegic solutions, only pure concentrations of the St Thomas' I and Bretschneider solutions under normothermic conditions were cytotoxic. The well-known protective effects of hypothermia against ischemia and reperfusion injury were both reproduced. Therefore, and even though cardioplegia failed to have any protective effect, probably owing to a severe metabolic inhibition, this model may be useful for studying myocardial protection.
Animals↗
Technetium-99m-sestamibi cellular uptake: passive or secondary active transport?
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Biological Transport↗
Comparison between technetium-99m-sestamibi and hydrogen-3-daunomycin myocardial cellular retention in vitro.
UNLABELLED: This study was undertaken to verify whether 99mTc-sestamibi uptake parallels that of 3H-daunomycin in cells treated with multidrug resistance (MDR) reversing agents. Since we have detected in a previous work a moderate typical MDR phenotype in rat cardiac cells, a model of cultured myocardial cells was used. METHODS: Newborn-rat cultured myocardial cells were incubated 120 min with the MDR-reversing agent verapamil 50 microM, PSC833 1 microM or S9788 10 microM alone or in combination, and the cellular retention of 3H-daunomycin and 99mTc-sestamibi was counted. RESULTS: Hydrogen-3-daunomycin cellular accumulation was never modified by more than 15% when compared to control values, while 99mTc-sestamibi decreased to 75% +/- 32% (m +/- s.d.) of controls in the presence of S9788 and to 44% +/- 19% when S9788 was associated with verapamil. CONCLUSION: The variations of 99mTc-sestamibi and 3H-daunomycin cellular accumulation induced by MDR-reversing agents in cultured myocardial cells can be dramatically different. While some MDR-reversing agents can significantly increase the 3H-daunomycin retention in cardiac cells, they have unexpected effects on that of 99mTc-sestamibi.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
In vitro detection of the MDR phenotype in rat myocardium: use of PCR, [3H]daunomycin and MDR reversing agents.
A decrease in the intracellular drug concentration in resistant cells as compared to sensitive cells is one of the characteristics of the MDR phenotype. P-glycoprotein (Pgp) is thought to be responsible for an active efflux of some lipophilic drugs such as anthracyclines. Anthracyclines such as daunomycin are highly effective anticancer agents but induce a well-described, while incompletely explained, cardiac toxicity. In this study, we investigated the MDR phenotype in rat myocardium in terms of gene expression, detection of Pgp and indirect evaluation of Pgp function. A clear mdr1a gene specific expression in rat cultured myocardial cells and cardiac tissue was detected by RT-PCR. The incorporation of [3H]daunomycin in myocardial cell cultures was studied with and without reversing agents. Daunomycin was found to have a high accumulation in cardiac cells illustrated by a Ci/Ce ratio of 2890. This high accumulation was moderately but significantly (p < 0.05) increased in the presence of a MDR reversing agent such as verapamil, PSC 833 or S9788. These results suggest that blockade of the Pgp in humans may result in an increased toxicity of several Pgp substrates in normal tissues like the myocardium.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Technetium-99m-sestamibi uptake in breast tumor and associated lymph nodes.
UNLABELLED: The aim of this study was to measure the accumulation of 99mTc-sestamibi in breast tumors and their axillary lymph nodes in patients undergoing scintimammography. METHODS: Eighteen patients who were scheduled for breast surgery underwent scintimammography with 740 MBq of 99mTc-sestamibi on the day before the operation. The next morning, reinjection with 370 MBq was performed. Immediately after the surgical procedure, the 99mTc activity of the tumor samples and, when available, the related lymph nodes was measured in a gamma counter. The samples were weighed and prepared for histological analysis. The activity of each sample was normalized to the mean activity of normal tissue samples obtained from the same patient. RESULTS: Among the 198 samples analyzed, the relative uptake of sestamibi was increased in 111 containing normal lymph nodes (1.80+/-0.79 vs 1.00+/-0.22, p<0.05), as well as in the seven containing invaded lymph nodes (2.01+/-0.83, p<0.01) and more dramatically, in the 22 with a carcinoma (5.64+/-3.06, p<0.001). In two patients with a benign lesion, both scintigraphy and counting demonstrated increased activity in the tumor. Four patients had negative scan results despite the presence of malignant tumor and a more than fourfold increase of sestamibi concentration in two of them. CONCLUSION: Technetium-99m-sestamibi concentrates strongly in breast carcinoma, sometimes even when the scan results appear normal, and mildly in lymph nodes, especially when invaded; it also concentrates in some benign tumors, possibly in relation to the presence of epithelial hyperplasia.
Adult↗
[Positron-emission tomography: role of 18F-fluorodeoxyglucose (18FDG) imaging in oncology].
There is a renewed interest in positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) since the development of large field of view cameras and the capability of regional distribution of 18FDG. This method may help solve three types of problems in clinical oncology: tumor diagnosis and extension assessment, prediction of treatment response and follow-up (diagnosis of recurrences and complications). The aim of this paper is to review the literature in this field. This technique is mostly used for brain, lung, rectal and breast tumors as well as for sarcomas. It is possible to diagnose an anaplastic transformation of a low grade glioma since 18FDG uptake correlates with the histological grade. 18FDG plays another important role in the evaluation of the brain tumor response to treatment and of the secondary effects or sequelae of this treatment. This technique is also useful in breast carcinomas: diagnosis in the case of a dense breast, detection of lymph nodes or other metastases which could modify the strategy. One of the most established roles of 18FDG PET is the diagnosis of rectal tumor recurrences. Furthermore, future results will probably confirm its usefulness in lung carcinoma, for the diagnosis and for treatment evaluation. Lastly, it plays an important role in soft tissue sarcomas at all stages of diagnosis and treatment. The results of the literature still have to be completed. However, if the capability of predicting tumor response to treatment is confirmed, this method will play an important role in patient management and will modify treatment strategies.
Cell Transformation, Neoplastic↗
[Identification of hibernating myocardium using 99m sestamibi tomoscintigraphy at rest].
The aim of this study was to assess the value of resting 99m Tc-Sestamibi scintigraphy for the detection of hibernating myocardium in zones of contractile dysfunction. Based on a series of 25 patients, 27 segments of supposedly hibernating myocardium were identified. All these segments corresponded to left ventricular wall motion abnormalities confirmed by contrast angiography and were perfused by a stenosed coronary artery: none of these zones were infarcted. Before revascularisation, comparison of the results of ventriculography and scintigraphy showed a correlation (p < 0.001) between the severity of regional contractile dysfunction appreciated by the center line method and the degree of myocardial hypofixation of 99m Tc MIBI. Three months after revascularisation, improvement of regional wall motion, assessed by control contrast angiography, was observed in 21 of the 27 segments studied (78%). Of these 21 segments, the viability of which was confirmed, 13 had a non-transmural uptake defect and 8 were normal on pre-revascularisation scintigraphy. The 6 segments without improvement at the 3 month control, had a transmural uptake defect on scintigraphy in 67% of cases. The authors concluded that when a residual uptake defect of 99m Tc sestamibi is present, viable myocardium may also be present.
Aged↗
[What are the indications for myocardial scintigraphy?].
Myocardial scintigraphy is a noninvasive technique of functional blood flow imaging whose indications are often poorly defined. The various practical modalities of the examination, as well as the tracers currently available in France are reviewed. The diagnostic value in the detection of coronary disease is then described, with emphasis on the complementarity of scintigraphy and the other techniques, particularly the stress test, and by trying to position scintigraphy in the context of the optimal diagnostic strategy. Finally, the prognostic value of scintigraphy, its value in post-infarction assessment and in the functional evaluation of known coronary stenoses are discussed.
Coronary Disease↗
[Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)].
A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight.
Adult↗
[Thrombolytic treatment of myocardial infarction. Data on the limitation of infarction size and left ventricular function].
Since its introduction in cardiovascular therapeutics, thrombolysis has established itself as an effective procedure of coronary reperfusion during the acute phase of myocardial infarction. Large scale clinical trials have demonstrated a clear cut reduction in mortality providing that the treatment is administered sufficiently early after the onset of symptoms. This reduced mortality is probably related to the limitation of infarct size and the conservation of ventricular function even though this relationship is not always analysed. Studies of infarct size and left ventricular function are difficult to perform and this is reflected in the number of different methods proposed. Apart from coronary reperfusion and its timing, other factors influence the definite size of the infarct, such as the development of a collateral circulation, the existence of cellular reperfusion lesions and the occurrence of reocclusion. The infarct size may be assessed by a number of methods, some simple (enzymes, electrocardiogram) but relatively inaccurate, others more promising but difficult to perform and more costly. Thallium 201 scintigraphy seems to be the best available method and our experience is based on these results. The reference method for the evaluation of left ventricular function is angiography but angioscintigraphy also provides information on global and regional function, the regional study being particularly valuable in the analysis of thrombolytic drug efficacy. A review of the literature shows that thrombolysis is associated with a reduction in infarct size compared with conventional therapy and with conservation of left ventricular function whichever thrombolytic agent is used.(ABSTRACT TRUNCATED AT 250 WORDS)
Humans↗
[Myocardial contusions in closed thoracic injuries: a prospective study].
Various laboratory investigations were assessed with respect to their accuracy in detecting myocardial contusion in patients with blunt chest trauma. All patients, aged between 18 and 50 years, admitted to the intensive care unit for flail chest, sternal fracture, pulmonary contusion, pleural or mediastinal lesion not requiring surgery, were included over a twelve month period. A complete cardiac assessment was carried out, including a physical examination, electrocardiogram, chest X-ray, enzyme assay (ALAT, ASAT, LDH, CPK and MB isoenzyme), two-dimensional echocardiography (2D-EC), thallium-201 scintigraphy. Myocardial contusion was diagnosed when an area of decreased or absent thallium-201 uptake was found in the scintigraphy. These latter results were compared with those obtained with the other investigations. Sixteen patients, mean age 34 years, were included; two who died before the end of the investigations were excluded. 2D-EC provided the most useful data (pericardial effusions in a third of the cases). The physical examination, enzyme assays, and chest films were of low value. The investigations carried out six months after the initial trauma showed that long term follow-up was not required. All patients were asymptomatic ten months after their trauma Although the diagnosis of myocardial contusion was made in half the cases using thallium-201 scintigraphy, 2D-EC provided reliable data and had the advantage to be carried out at the patient's bedside.
Adult↗