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J F Chatal

Publications and source records attributed to J F Chatal.

At least 91 records · Page 5Linked to original sources
PubMed1989

Screening for multiple endocrine neoplasia type 2a with DNA-polymorphism analysis.

Multiple endocrine neoplasia type 2a has been shown to be genetically linked to a locus near the centromere of chromosome 10. The availability of polymorphic DNA probes for the region permits the use of restriction-fragment-length polymorphisms (RFLP) to identify carriers of the gene for this cancer syndrome. As part of a French national program, DNA probes were used in a genetic-linkage study of 130 members of 11 families of European and North African origin. In these families there was no recombination between the mutation causing multiple endocrine neoplasia type 2a and two of the three probes used. All 11 families were informative for at least one of the three markers, and linkage information was adequate to provide genetic counseling to 8 families. We found that RFLP analysis is much more useful in predicting the carrier state than conventional endocrine challenge, especially in younger people, but accuracy is maximal when both methods are employed. We conclude that genetic screening allows the identification of those who are at risk for multiple endocrine neoplasia type 2a at any age with a high level of certainty. After initial screening with DNA, tests for early neoplastic change may be directed toward those determined to be at high risk.

Carcinoma↗
PubMed1989

Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma.

The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.

Animals↗
PubMed1989

Biodistribution of indium-111-labeled OC 125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian carcinomas.

The biodistribution of 111In-labeled monoclonal antibody (MAb) OC 125 was studied after i.p. injection in 28 patients who underwent surgery for ovarian carcinoma. Group I (eight patients) received intact 111In-labeled OC 125 MAb, Group II (three patients) intact 111In-labeled irrelevant NS, Group III (five patients) intact 111In-labeled OC 125 MAb associated with 20 mg of the same unlabeled MAb and Group IV (12 patients) F(ab')2 fragments of 111In-labeled OC 125 MAb. The patients were operated on 1 to 3 days after i.p. injection, and the surgeon removed large tumor fragments and/or small tumor nodules and, in some patients, collected the residual perfusion fluid from which malignant cell clusters were isolated. Uptake by large tumor fragments at 24 h was low: 0.0031 +/- 0.0032% injected dose per gram (%ID/g) for Group I and 0.0024 +/- 0.0022%ID/g for Group IV. It was moderately higher than that of Group II (0.0014 +/- 0.0006%ID/g) and Group III (0.0015 +/- 0.0007%ID/g). Uptake by small tumor nodules (0.1302 +/- 0.0802%ID/g at 72 h for Group I) and malignant cell clusters (median: 0.3322, with a maximum value of 4.1614%ID/g at 24 h for Group IV) was markedly higher. Tumor-to-normal tissue ratios with OC 125 MAb [intact or F(ab')2 fragments] ranged between 0.1 and 8.5 for large tumor fragments and 2 and 8,700 for small tumor nodules and malignant cell clusters. It would thus appear that RIT is feasible if an appropriate radionuclide can be selected for antibody labeling.

Adult↗
PubMed1989

Histological correlation of 17 prospective immunoscintigraphies of recurrences of colorectal carcinomas using indium-111-labeled anti-cea and(or) 19-9 monoclonal antibodies.

Seventeen patients (mean age 55 years) with suspected recurrence in previously operated and histologically confirmed colorectal adenocarcinomas were explored by immunoscintography (IS) associating planar and emission computed tomography (ECT) and using the 111In-labeled anti carcinoembryonic antigen (CEA) and(or) 19-9 monoclonal antibodies (MoAbs). The results of IS were compared blind with those of computed tomography (CT) and ultrasonography (US). The final diagnosis of recurrence and(or) metastasis was done in 16 cases by second-look surgery and in another patient by rectal biopsy. Overall per-patient sensitivity for the pelvis and extrahepatic abdomen was 69% for IS and 31% and 25% respectively for computed tomography and ultrasonography. No false positive of IS, as well as US and CT, for the pelvis and the extrahepatic abdomen was seen. Based on the number of anatomical sites tested, sensitivity of IS was 91% in the pelvis. In our series, scintigraphic computer subtraction did not allow adequate resolution of the problem of intense liver uptake of 111In-labeled MoAbs. It is concluded that IS using 111In-labeled anti CEA and(or) 19-9 MoAbs should be carried out prospectively in patients at high risk of recurrence of colorectal cancer.

Adenocarcinoma↗
PubMed1989

Biodistribution of an anti-interleukin 2 receptor monoclonal antibody in rat recipients of a heart allograft, and its use as a rejection marker in gamma scintigraphy.

Anti-interleukin-2 receptor monoclonal antibodies have been shown to prevent allograft rejection. This paper reports on the biodistribution of a mouse MoAb directed at the 55 Kd alpha chain of rat interleukin-2 receptor (IL2-R) during allograft rejection. Only a low percentage (approximately 1%) of intact 125I-labeled MoAb was detected in the rejected graft, and irrelevant control IgG1 was found at a similar level. This suggests that most of the injected intact MoAb bound to graft tissue via its monomorphic Fc segment. In contrast, OX39 F(ab')2 fragments showed a preferential localization in the rejected allograft and did not bind to the LEW-to-LEW syngeneic heart graft. Irrelevant F(ab')2 did not concentrate in the allogeneic graft. Accordingly, F(ab')2 fragments from OX39 or irrelevant MoAb were used for gamma-scintigraphy on allograft recipients together with biodistribution studies. Results show that scintigraphy was able to detect allograft accumulation of 131I OX39 F(ab')2, whereas no imaging was obtained when OX39 F(ab')2 was used in the syngeneic combination or when irrelevant 131-IgG1 F(ab')2 was given to allograft recipients. This method, applied to the clinical situation, could be of interest for detection of early graft rejection episodes by immunoscintigraphy using reagents specific for activation determinants on lymphocyte membranes, such as anti-interleukin-2 receptor MoAb.

Animals↗
PubMed1988

Gd-25 DTPA-MAb, a potential NMR contrast agent for MRI in the xenografted nude mouse: preliminary studies.

Monoclonal antibodies (MAbs) 19-9 and 73-3 specific for human colon adenocarcinoma were labelled with a high number of gadolinium atoms. Twenty five DTPA were chelated per MAb, with only slight loss of immunoreactivity. The NMR contrast agent Gd-25 DTPA-MAb 19-9 or 73-3 ([Gd] 17 mumole/kg, [MAb] 60 microM) was injected into nude mice bearing human colon adenocarcinoma (SW948). Tumours were removed 24 hr after injection and T1 was measured in vitro. T1 relaxation time varied according to MAb specificity against tumour targets; T1 decreased 20% for MAb 19-9 and MAb 73-3 with SW948 tumour. Imaging was performed with this model. Very good contrast was obtained 24 hr after Gd-25 DTPA-MAb injection.

Animals↗
PubMed1988

Aerosol-perfusion lung scintigraphy: value of ventilation subtraction.

99Tcm-labelled aerosol ventilation and 99Tcm-macroaggregate albumin (99Tcm-MAA) perfusion can be performed in the diagnosis of pulmonary embolism (PE). If both examinations are performed on the same day, the superposition of activity from the first scintigraphic examination might mask defects in the second. In this study, 106 examinations were carried out for suspected PE. Aerosol ventilation was performed first with 20 to 30 mCi 99Tcm-labelled rhenium sulphur (four views, 200,000 counts). Immediately afterwards, with the patient remaining in the same position, 5 to 7 mCi of 99Tcm-MAA were injected (four views, 400,000 counts). After normalization, aerosol activity was subtracted from perfusion images and unprocessed perfusion (UP) and ventilation subtraction perfusion (SP) images were compared. Interobserver diagnostic reproducibility between three readers was calculated both for UP and SP images. Intraobserver reproducibility between UP and SP images was calculated for each reader. Interobserver reproducibility was comparable for SP and UP images. Intraobserver reproducibility was good. Thus, whether ventilation was subtracted or not from perfusion images, there was no appreciable effect on perfusion defect detection. However, some perfusion abnormalities showed up more clearly on SP images. Perfusion can be performed immediately after aerosol ventilation; the images thus obtained are reliable for interpretation, and subtraction of ventilation is not necessary.

Aerosols↗
PubMed1988

[Treatment of malignant pheochromocytoma by 131-I-metaiodobenzylguanidine].

Twelve patients (2 with only bone metastases, 3 with only soft tissues metastases and 7 with bone and soft tissues metastases) were treated with 131-I-MIBG (specific activity: 20 mCi/mg), 100 to 200 mCi every 3-6 months. A dosimetric study was carried out before each administration. The follow-up ranged from 6 to 24 months and the number of doses ranged from 1 to 8, with 1.85-9 GBq per administration and a cumulative activity of 1.85-62. 2 GBq according to patients. The cumulative absorbed activity ranged from 850 to 9700 cGy. The following side effects were observed: a bone marrow hypoplasia (1 patient) and a transient increase in catecholamines (3 patients). The treatment was successful in 7 patients (3 with soft tissue metastases, 3 with bone and soft tissue metastases and one with bone metastases). This success consisted in clinical improvement and a decrease greater than 50% of hormonal values in the 7 patients and a decrease greater than 50% of tumoral masses in only 3 patients. No complete remission was obtained at this stage of the study. The disease recurred in 1 patient after a year of partial remission. There was no clear-cut relation between the number of doses and the results. This study shows that 131-I-MIBG can give encouraging though limited results.

3-Iodobenzylguanidine↗
PubMed1987

Immunoscintigraphy of recurrences of gynecologic carcinomas.

In a first, retrospective study, 15 patients with known ovarian carcinoma were injected with 131I-OC 125 F(ab')2 monoclonal antibody (MAb). The sensitivity of immunoscintigraphy based on the number of the tumor sites was 67% (12/18). In a second, prospective study, 29 patients with gynecologic carcinoma were injected with 131I-OC 125 F(ab')2 (24) or 131I-19-9 F(ab')2 (5) MAbs according to the histologic type. Based on the number of tested anatomic sites, sensitivity was 72% and specificity 86%. In two patients injected with both 131I-OC-125 F(ab')2 and 125I-NS F(ab')2 (nonspecific immunoglobulin) 1 and 4 days before tumor resection, tumor uptake of the specific antibody was 2.2 and 4.5 times greater than that of NS. Immunoscintigraphic results were complementary with those of ultrasonography and computed tomography. Finally, in one patient injected successively with 131I-OC 125 F(ab')2 and 111In-DTPA-OC 125 F(ab')2, the recurrent tumor was visualized with both radionuclides, with 111In providing better abdominal tumor contrast but causing much greater liver radioactivity than 131I.

Adenocarcinoma↗
PubMed1986

99mTc-DTPA and 99mTc-rhenium sulfur aerosol compared as adjuncts to perfusion scintigraphy in patients with suspected pulmonary embolism.

Two radiopharmaceuticals, 99mTc-DTPA (D) and 99mTc-rhenium sulfur (R), were evaluated with a nebulizer delivering submicronic particles. Seventy-seven patients were examined (42 D, 35 R). For all patients, the examination began with a ventilation study. Immediately after the last ventilation view, 99mTc MAA was injected. Aerosol performance was assessed in 37 D and 17 R. Nebulization yield was 8.98% for D and 9.31% for R. A lung clearance study was performed in 12 patients for D and in 12 different patients for R. The lung clearance was 0.22%/min for R and 2.35%/min for D. The quality of ventilation and the quantification of bronchial and gastric activity were evaluated; the difference between the two groups was not statistically significant. It may be concluded that radioaerosols allow good quality images to be obtained. The yield of the nebulizer is adequate, so that nebulization of 20 mCi delivers approximately 2 mCi of aerosol activity to the lung. When pulmonary embolism is being investigated, R, due to its slower lung clearance, would appear to be preferable to D for patients suspected of increased bronchoalveolar permeability, especially if the time between nebulization and recording is greater than 10 min.

Adult↗
PubMed1986

Immunotherapy of gastrointestinal cancer with monoclonal antibodies.

Twenty patients with widespread metastatic colorectal carcinoma were infused with 500 mg of the cytotoxic IgG2a monoclonal antibody 17-1A preincubated with autologous peripheral blood leukocytes. Ten patients showed no benefit from such therapy and ten died, with a mean survival time of 7.6 +/- 4.5 months after treatment and a median survival of 6 months. In ten additional patients, the course of disease was modified by antibody therapy; disease in five of these patients stabilized, while tumor size in the other five patients decreased after therapy. Median actual survival in this group of ten patients is presently 24 months; four of these patients died of disease progression within a mean of 15 +/- 5 months. Duration of response was 10.5 +/- 6.7 months after antibody treatment. Treatment tolerance for these 20 patients was excellent in all but one patient, who experienced an anaphylactic reaction during a second infusion with 17-1A.

Adult↗
PubMed1986

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors.

Adenocarcinoma↗
PubMed1986

[Comparison of MIBG scintigraphy and computerized tomography in the localization of pheochromocytomas].

Ninety-nine patients suspected of having pheochromocytoma were studied with MIBG scintigraphy and in 92 of them were studied with computed tomography. In 49 patients, the diagnosis was ruled out, in 3 patients it remained doubtful, and in 47 patients it was confirmed. Two patients had epinephrine--and/or norepinephrine--non-secreting tumors and 45 had secreting pheochromocytomas. In these latter patients, there were 4 scintigraphic false-negatives, all intra-adrenal, and 4 computed tomography false-negatives, 3 extra-adrenal and 1 intra-adrenal. For about 80% of the patients and/or the tumor sites, both methods were thus in agreement. They were complementary in the remaining 20%. The advantage of scintigraphy is to screen the whole body with high specificity and to locate extra-adrenal sites or metastases of pheochromocytoma with better accuracy than computed tomography. The limits of scintigraphy are the possibility of false-negatives in around 10% of patients whereas computed tomography visualizes more than 95% of intra-adrenal tumors.

3-Iodobenzylguanidine↗
PubMed1986

Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract.

Two monoclonal antibodies with specificity for carcinoembryonic antigen and Ca 19-9 gastrointestinal tract tumor associated antigens were infused after iodination with 125I and 131I, respectively, in six patients 3 days and in one patient 4 days before radical surgery for colon or rectal carcinoma. Biopsy specimens from tumor, normal colon, fat, muscle, and skin along with a blood sample were excised at surgery and counting was performed for gamma emission. Fragments were then studied by two independent pathologists for immunohistochemical expression of corresponding antigens using the avidin-biotin peroxidase complex. A correlation study was thereafter performed between the amount of antibody bound in vivo, expressed as the percentage of injected dose per gram of tissue and the quantitative expression of tumor associated antigens, taking into account both the percentage of cells expressing the antigen and intensity of staining. For this limited number of patients a good correlation was found between amount of targeted antibodies and amount of expressed antigens. For carcinoembryonic antigen, r values were 0.69 and 0.90 for each pathologist (with an r value of interobserver correlation of 0.74); for Ca 19-9, values of 0.78 and 0.84 were obtained for each observer, with an interobserver r value of 0.97. Based on this limited study, it may be assumed that the possibility of imaging a given tumor is in part correlated to intensity of antigenic expression at the tumor site; other parameters, like tumor vascularization and blood flow for instance, are, however, to be considered for accessibility of antibodies to corresponding antigens.

Antibodies, Monoclonal↗