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Biomedical subjects

J F Chatal

Publications and source records attributed to J F Chatal.

At least 73 records · Page 4Linked to original sources
PubMed1992

Use of multi-cell spheroids of ovarian carcinoma as an intraperitoneal radio-immunotherapy model: uptake, retention kinetics and dosimetric evaluation.

The purpose of this study, using multi-cell spheroids as an in vitro model of micrometastases of ovarian carcinoma for i.p. radio-immunotherapy, was to measure the uptake and retention kinetics of 111In-labeled F(ab')2 fragments of OC125 monoclonal antibody (MAb) in spheroids of the NIH:OVCAR-3 cell line and to estimate absorbed doses with beta-emitting radionuclides (kinetics was assumed to be similar to that of indium-111). With 0.2-mm-diameter spheroids at different MAb concentrations the highest binding value was determined. Retention kinetics showed a biological half-life of 50 hr. These data were used to calculate absorbed doses by integration of Berger's latest-point kernels. Mean absorbed doses when spatial distribution was considered to be uniform at the surface (no penetration) or throughout the spheroid (total penetration) were, respectively, 247 and 417 Gy with 153Sm, and 90 and 135 Gy with 90Y. Thus, the use of a similar MAb concentration and specific activity in patients should lead to high absorbed doses in i.p. radio-immunotherapy of micrometastases.

Antibodies, Monoclonal↗
PubMed1992

Does immunoscintigraphy serve clinical needs effectively? Is there a future for radioimmunotherapy?

Since 1980, immunoscintigraphy has been performed in thousands of patients, and its clinical value has been demonstrated for selective indications in malignant (early detection of recurrences of colorectal and ovarian carcinomas) and non-malignant (cardiovascular and inflammatory) pathology. However, many clinicians are not yet very convinced of its efficiency. Opinions range between favourable interest and marked scepticism. The causes of this inconclusive verdict include an often moderate target-to-background ratio in images, the immunogenicity of injected murine antibodies and the fact that a true benefit for the patient has not yet been clearly demonstrated in large series of patients. Future prospects could significantly improve this and involve the reduction of non-specific activity in normal tissues (to improve disease target contrast and thus make image interpretation easier) and the decreased immunogenicity of injected immunoconjugates (to permit repetition of examinations). Radioimmunotherapy, an innovative and promising approach, is still limited by numerous problems. The results of clinical studies are still inconclusive, being encouraging only for specific indications. In the future, pre-targetting techniques should allow the rapid elimination of radioactivity from normal tissues, resulting in a significant increase in tumour-to-normal tissue ratios. Progress is also required in the choice of radionuclides and labelling techniques and in methods for dosimetric estimations. The clinical indications of radioimmunotherapy after systemic injection will concern mainly radiosensitive tumours such as lymphomas, small-cell lung cancers and neuroblastomas. After endocavitary injection, radioimmunotherapy could prove efficient in the treatment of micrometastases of ovarian carcinomas. For all indications, this new approach should be combined with other therapeutic modalities.

Evaluation Studies as Topic↗
PubMed1992

Comparison of technetium-99mC and phytate aerosol in ventilation studies.

The image quality obtained with technetium-99mC aerosol (Technegas) was evaluated and compared with that obtained with 99mTc-phytate aerosol generated by a jet nebulizer. Fifty patients underwent ventilation scanning after inhalation of each aerosol (mean interval of 3 days). Four views (anterior, posterior, left and right posterior oblique) were recorded with 200 k precounts. Both sets of images were blindly compared for (i) qualitative evaluation of images, (ii) quantitation of penetration (PI) and heterogeneity (HI) indices and (iii) assessment of ventilation state. Peripheral penetration was the same in 64% of cases, greater with 99mTc-C in 27% and greater with 99mTc-phytate in 9%. The use of 99mTc-C led to fewer and less intense foci of bronchial or gastric activity. The differences for 99mTc-C and 99mTc-phytate, respectively, between mean PI (0.78 vs. 0.70) and HI (15 vs. 18) were not significant. Consideration of all the parameters indicates the overall superiority of 99mTc-C. The final interpretation of the lung ventilation scans was, however, similar with both tracers.

Administration, Inhalation↗
PubMed1992

Correlative imaging study in the diagnosis of ovarian cancer recurrences. The INSERM Research Network (Nantes, Rennes, Reims, Villejuif, Saclay), France.

A correlative imaging study was carried out in 61 female patients previously treated for ovarian carcinoma. Upon suspicion of recurrence, abdominopelvic immunoscintigraphy (IS) using F(ab')2 fragments of indium-111-labelled OC 125 monoclonal antibody was performed in all patients, Ultrasonography (US) and computed tomography (CT) were performed 53 and 37 times, respectively. The diagnostic accuracy of the different imaging techniques was studied per site (abdomen and pelvis) and per patient. The diagnostic accuracy of planar scintigraphy (PS) was slightly lower than that of emission computed tomography (ECT): 66% vs 73% for abdomen, 65% vs 72% for pelvis, and 78% vs 84% in analysis per patient. The accuracy of IS (PS and ECT combined) was markedly better than that of US and CT for abdomen (IS = 73%; US = 30%; CT = 47%), pelvis (IS = 73%; US = 37%; CT = 52%) and analysis per patient (IS = 85%; US = 43%; CT = 59%). The results of IS and morphological imaging techniques (MIT: US and/or CT) were correlatively analysed with the frequency of recurrence. When IS and MIT were both negative, the frequency of non-recurrence was 14/23 for abdomen, 7/12 for pelvis and 8/13 in analysis per patient. On the other hand, when both IS and MIT were positive, the frequency of recurrence was high (9/9 for abdomen, 17/21 for pelvis and 24/26 for analysis per patient). It was also found that a positive IS associated with a negative MIT was still highly suggestive of recurrence (17/21 for abdomen, 16/22 for pelvis and 17/19 for analysis per patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

MIBG scintigraphy of a patient with pheochromocytoma on labetalol therapy.

A patient with pheochromocytoma was studied by MIBG scintigraphy while on labetalol therapy, which has been reported to interfere with imaging. Serial imaging was performed at 2, 18, 25, and 90 hours to obtain time/activity curves. Blood samples were taken at each imaging study to determine activity counts. Tumor activity per gram of tissue (surgery 116 hours after injection) was compared with blood activity. Tumor and blood activity decreased concurrently, whereas the decrease in peritumoral activity was faster, thus providing transiently improved contrast on 18- and 25-hour images. The diagnostic implications of these results are discussed.

3-Iodobenzylguanidine↗
PubMed1992

Anti-beta HCG abdominopelvic immunoscintigraphy in patients with resistant gestational trophoblastic disease.

The clinical utility of abdominopelvic immunoscintigraphy (IS) using anti-beta HCG-labelled monoclonal antibodies was evaluated in six patients with resistant gestational trophoblastic disease and no common pathological site. Five patients with abnormal retrovesical uptake had persistence of uterine trophoblastic disease confirmed on hysterectomy. Four of these patients are now in remission. It is concluded that IS provides a useful indication for surgery when a single abnormal uptake site is found.

Abdomen↗
PubMed1992

Immunoscintigraphy using 111In-labeled F(ab')2 fragments of anticarcinoembryonic antigen monoclonal antibody for detecting recurrences of medullary thyroid carcinoma.

The only current possibility for curing medullary thyroid carcinoma (MTC), especially recurrences, is total surgical removal. Early positive diagnosis of recurrences is now possible by monitoring tumor markers such as thyrocalcitonin and carcinoembryonic antigen (CEA). However, preoperative topographic diagnosis of such recurrences remains an unresolved problem. Immunoscintigraphy (IS) using an anti-CEA monoclonal antibody is a new approach that complements morphological imaging, i.e. ultrasonography, computerized tomography, and magnetic resonance imaging. In this study, IS by means of an 111In-labeled anti-CEA monoclonal antibody F(ab')2 was performed nine times in eight patients. True positives were obtained five times (one case of cervical involvement confirmed by surgery, three cases of mediastinal involvement confirmed by computerized tomography, magnetic resonance imaging, and surgery, and one case of bone metastasis, one of them was revealed neither by x-ray nor by conventional bone scan). The remaining four tests gave a false positive, a true negative, a probably false negative, and one unconclusive result. We conclude that IS is helpful in diagnosing sites of MTC recurrence and should accompany other examinations in the evaluation of lesions.

Adult↗
PubMed1991

A new tumor-associated antigen expressed on breast carcinomas, defined by monoclonal antibody BCA 227.

After immunization of mice with the human breast carcinoma cell line MCF-7, we produced monoclonal antibody (mAb) BCA 227, which allowed us to characterize a new tumor-associated antigen. This molecule is strongly expressed by well differentiated mammary carcinoma cell lines and by some other tumor cell lines of epithelial origin. Immunohistological study of frozen sections of different tissues and tumors confirmed its expression by tumor cells of epithelial origin, particularly infiltrating duct carcinomas of the breast. The antigen is also expressed, to a lesser extent, by some normal epithelial cells. Its biochemical characterization revealed a Mr 71,000 protein without an N-linked sugar moiety. Six to 40 x 10(3) binding sites are present on breast tumor cell surfaces. Although mAb BCA 227, which was found to be of the IgG2a isotype, did not mediate antibody-dependent cell-mediated cytotoxicity with either human or mouse effector cells, a 50% inhibition of SK-BR5 tumor growth was obtained in nude mice, suggesting that another mechanism is responsible for this inhibition. Biodistribution studies of radiolabeled F(ab')2 fragments of mAb BCA 227 in tumor-bearing nude mice showed a preferential localization in the tumor. All these data are in favor of the use of mAb BCA 227 as an immunodiagnostic tool for breast cancer.

Animals↗
PubMed1991

[Fixation of Indium111-labeled antifibrin monoclonal antibody on the vegetation in endocarditis: evaluation in a rabbit model].

The uptake of a 111In labelled antifibrin antibody was studied in left ventricle endocarditis on a rabbit model. The immunospecificity of the antibody for the cardiac vegetations is favorable, exhibiting an uptake at least 4 times that of blood, or myocardium. A planar scintigraphy of the opened left ventricle showed a radionuclide imaging of vegetations, according to anatomical lesions. The use of antifibrin monoclonal antibodies could prove helpful to improve the specificity of valvular lesions visualized by echocardiography, or to detect the small vegetations at the early stage of acute endocarditis.

Animals↗
PubMed1991

Reproducibility of image interpretation in immunoscintigraphy performed with indium-111- and iodine-131-labeled OC125 F(ab')2 antibody injected into the same patients.

An important criterion for the clinical use of a new imaging technique is the correct reproducibility of interpretation. Forty-six paired immunoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence using F(ab')2 fragments of OC125 antibody labeled first with indium-111 and then with iodine-131. Planar scintigraphy (PS) and emission computed tomography (ECT) images were interpreted blindly and separately by three observers, and reproducibility was evaluated by a kappa concordance index. Intra- and interobserver reproducibility were generally satisfactory (kappa values of 0.6 and 0.7, respectively). Binomial analysis of kappa values for ECT showed the superiority of indium-111 for intraobserver (p = 0.035) and interobserver (p = 0.0039) study. However, for PS there was no significant difference in reproducibility with the two radionuclides.

Adult↗
PubMed1991

Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease.

The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT.

Antibodies, Monoclonal↗
PubMed1990

In vitro therapeutic targeting of neuroblastomas using 125I-labelled meta-iodobenzylguanidine.

The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m-IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK-N-SH, SK-N-MC, LAN I) showed that only the SK-N-SH line retained iodine-125 m-IBG (125I-m-IBG) significantly. Fifty-five percent of the initial activity was retained after 1 hr incubation at a concentration of 10(-7) M of m-IBG (specific activity: 1,480 MBq/mg). Beyond this value, m-IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m-IBG and showed that a low percentage (3 to 5%) of SK-N-SH cells strongly retained m-IBG. Cytotoxicity tests showed that SK-N-SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I-m-IBG, whereas no toxic effect on SK-N-MC cells was found at the same activity. Moreover, the toxic effect observed in the SK-N-SH line was clearly related to the use of 125I-m-IBG since the same activity of 1,500 KBq of non-coupled 125I was without effect. For the latter line, colony-forming capacity was reduced for activities of 150 and 1,500 KBq of 125I-m-IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m-IBG was, however, limited in non-saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m-IBG is indicative of the heterogeneous cellular composition of the SK-N-SH line.

3-Iodobenzylguanidine↗
PubMed1990

Multi-centre immunoscintigraphic study using indium-111-labelled CEA-specific and/or 19-9 monoclonal antibody F(ab')2 fragments.

Six European nuclear medicine centres performed immunoscintigraphy first retrospectively in 34 patients using indium-111-labelled carcinoembryonic antigen (CEA)-specific and/or 19-9 F(ab')2 fragments. Results for sensitivity and specificity in tumour sites were 94% and 87%, respectively, for the pelvis and 73% and 100% for the extrahepatic abdomen. A second prospective series concerned 58 other patients previously operated on for colorectal adenocarcinoma (27 colon, 31 rectum). Two-thirds of these patients had a suspected recurrence signalled by an isolated rise in tumour markers, and 46 patients examined by immunoscintigraphy, X-ray computed tomography and ultrasonography were found to have a recurrence (a total of 62 tumour sites). Sensitivity and specificity with immunoscintigraphy were 90% and 97%, respectively, for the pelvis and 62% and 95% for the extrahepatic abdomen. For 29 patients injected with CEA-specific fragments, sensitivity was 90% and specificity 94% for the pelvis. For 25 patients injected with 19-9 fragments, pelvic sensitivity and specificity were 80% and 100%, respectively, whereas sensitivity for the extrahepatic abdomen was only 29% since several cases of peritoneal carcinosis were not visualized. In the prospective series, comparison of the three imaging techniques for all tumour sites (including liver and in 5 cases thorax) gave a sensitivity and specificity of 82% and 91%, respectively, for immunoscintigraphy, 52% and 95% for X-ray computed tomography and 59% and 100% for ultrasonography. These results thus confirm the advantage of using 111In-labelled CEA-specific or 19-9 to visualize and localize recurrences of colorectal cancer.

Adenocarcinoma↗
PubMed1990

Feasibility study of radioimmunoguided surgery of colorectal carcinomas using indium-111 CEA-specific monoclonal antibody.

The study was undertaken to define the potential use of indium 111 carcinoembryonic antigen-specific antibody labelled [CEA F(ab')2] for the radioimmuno-detection of colorectal carcinoma using an intraoperative hand-held gamma probe. The use of a linear radioactive source allowed optimization of physical characteristics. The best results regarding sensitivity and resolution were obtained using a 5-mm thick tungsten alloy collimator. A simulation study with a liver phantom (22 MBq or 0.6 mCi) was performed to determine the effect of side scatter as opposed to direct background and showed that it is possible to detect small radioactive targets (3.7 KBq or 0.1 mu Ci) 4 cm from the phantom. A clinical study performed with ten patients showed that tumours with good uptake of CEA-specific antibody could be detected with sufficient contrast in two patients when the probe was used. Results of a biodistribution study performed after tumour fragment or normal tissue countings in a well counter showed high tumour uptake (above 8 x 10(-3) injected dose/g) and tumour-to-normal tissue ratios (between 2.5 and 20) in five patients. Results with the probe showed markedly lower ratios. There was no correlation between absolute tumour uptake and the count rates of tumour measured intraoperatively. This can be attributed to the degradation of depth resolution resulting from the high energy photopeak of gamma-emitting 111In.

Adenocarcinoma↗
PubMed1990

Comparison of technetium-99m aerosol and krypton-81m in ventilation studies for the diagnosis of pulmonary embolism.

A new method of producing aerosols (technegas) in which 99Tcm is bound to carbon atoms (99Tcm-C) was evaluated by comparing 99Tcm-C images with those obtained with 81Krm in the same patients. Twenty-five patients with suspected pulmonary embolism (PE) were studied. Immediately after the last 99Tcm-C view, the patients remained in supine position and inhaled 81Krm at tidal volume. Immediately after the 81Krm ventilation views were recorded, 4-7 mCi of MAA were injected IV. The same four views (ant, lop, rop, post) were recorded after inhalation of 99Tcm-C and 81Krm (200 kcounts) and 99Tcm MAA injection (400 kcounts). The mean penetration index of 99Tcm-C (0.91) was lower than that of 81Krm (1.04) (P less than 0.03). The apex to base lung distribution of 99Tcm-C and 81Krm appeared to be similar. The mean heterogeneity of 99Tcm distribution was 23, greater than that of 81Krm (14) (P = 10(-4)). The 99Tcm-C ventilation image quality was considered very good for 16 patients and good for 6 others. Significant foci of high bronchial uptake were infrequent. Interpretation of the examinations performed after inhalation of 99Tcm-C and 81Krm was concordant in all cases. No patient had an 81Krm/99Tcm MAA examination suggestive of PE when 99Tcm-C/99Tcm MAA indicated a low probability of PE, and vice versa. 99Tcm-C aerosols enable good quality ventilation images to be obtained in nearly all cases. Thus 99Tcm-C aerosols could be used in preference to 81Krm in ventilation studies for the diagnosis of PE.

Administration, Inhalation↗
PubMed1990

[New techniques of scintigraphic imaging].

The purpose of scintigraphic imaging is not to explore the morphology of an organ (or its abnormalities) but rather its functional and metabolic characteristics. It is thus important that a molecular structure (e.g., a hormonal receptor or an antigen) closely linked to the functional activity of an organ or tissue be targeted on its cell surface. Such diagnostic targeting requires the synthesis and labeling of a radiopharmaceutical substance specific for the receptor or antigen in question. It also requires a detection system adapted to count rates and signal-to-background ratios (generally moderate). The synthesis of new radiopharmaceutical agents, a critical stage for the future of nuclear medicine, is a long and often risky process in which success is difficult to foresee. Radiolabeling must be stable in vitro and in vivo, and the radiopharmaceutical must subsequently retain its capability of recognizing the targeted molecule. In endocrinology, the exemplary achievement in this direction has been the synthesis of 131I-6-iodomethylnorcholesterol and 131I-metaiodobenzylquanidine for functional scintigraphy of the adrenal cortex and medulla. Progress in detection equipment has been marked by the development of monophotonic tomoscintigraphy, using gamma cameras with a revolving head to obtain slices in different spatial planes showing the distribution in the organism of the injected radiopharmaceutical agent.

Antibodies, Monoclonal↗
PubMed1990

[Role of imaging in the exploration of the adrenal glands].

Currently, the major method of adrenal gland imaging is computed tomography. This method allows demonstration of normal adrenals and the diagnosis of adrenal masses (if these are greater than 1 cm in diameter). The examination should be directed by clinical signs and known laboratory investigations. Computed tomography is therefore the first line investigation to perform. Certain lesions may be better demonstrated by other methods: MRI and MIBG scintigraphy offer a greater specificity in the investigation of pheochromocytomas. In addition, scintigraphy can identify possible ectopic tumours or recurrences. Selective catheterisation of the adrenal veins allows aldosterone and cortisone secretions to be assayed. There remains the problem of the incidental finding of adrenal masses in either an asymptomatic patient or in the context of investigation of spread of a know cancer. These lesions may benefit from diagnostic percutaneous guided biopsy.

Adrenal Gland Neoplasms↗