Search PubMed⌕ Search

Biomedical subjects

J F Chatal

Publications and source records attributed to J F Chatal.

At least 109 records · Page 6Linked to original sources

Comparison between 131I and 111In as radiolabels for monoclonal antibodies in immunoscintigraphy of tumor bearing nude mice.

F(ab')2 fragments of monoclonal antibody (MoAb) 19-9 with specificity for human colorectal adenocarcinomas were labeled with 111In or 131I and infused into nude mice bearing the human adenocarcinoma HT 29 in order to compare their preferential biodistribution according to the radiolabel used. Animal tissue distribution measured one day and five days after infusion showed that tumor accumulation was greater for 111In than for 131I. However, non specific binding of 111In labeled MoAb 19-9 was also greater in normal tissue than 131I labeled antibody, except in blood. Therefore, the tumor/normal tissue ratios were to the advantage of 131I MoAb 19-9 and a better contrast was obtained on imaging with 131I as compared to 111In labeled MoAb 19-9. Based on this experimental model 111In does not seem to be the optimal candidate for tumor imaging using radiolabeled MoAb.

Adenocarcinoma↗

Enzyme-linked immunosorbent assay to monitor colorectal carcinoma patients treated with a monoclonal antibody (17-1A).

An enzyme-linked immunosorbent assay (ELISA) was compared to a radioimmunoassay (RIA) for the detection and quantification of mouse monoclonal antibody MoAb 17-1A and for measurement of the host response (i.e. anti-mouse immunoglobulin in sera from patients receiving immunotherapy with MoAb 17-1A. Comparable sensitivity and reproducibility were noted with RIA and ELISA but ELISA was more rapid to perform than RIA. Thus quantitative ELISA compared favorably with the RIA for MoAb detection.

Animals↗

Complementary roles of immunoscintigraphy and ultrasonography.

A female patient raised the problem of detection of a primary tumor after discovery of multiple nodular, apparently metastatic, lung densifications. Immunoscintigraphy using an anti-CEA antibody revealed two hot spots above and to the right of the urinary bladder. Ultrasonography showed a right ovarian cyst and normal echo texture for the uterus. Surgery confirmed the diagnosis of a right ovarian cyst with a macroscopically normal uterus. Pathological examination demonstrated adenoacanthomatous involvement of the walls of the ovarian cyst and of the uterus. The results of immunoscintigraphy were thus determinant in visualizing the expression of CEA by the ovarian cyst and by the uterus and thus in suggesting their malignancy.

Adenocarcinoma↗

Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice.

Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the 131I-labeled MoAbs and an irrelevant 125I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 microCi/microgram by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached is maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab')2 antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

Animals↗

Comparison of iodobenzylguanidine imaging with computed tomography in locating pheochromocytoma.

Ninety-nine patients suspected of having pheochromocytoma were studied with [131I]metaiodobenzylguanidine scintigraphy, and 92 of them were studied with computed tomography (CT). In 49 patients, the diagnosis was ruled out; in 3 patients, it remained doubtful; and in 47 patients, it was confirmed. Two patients had tumors that did not secrete epinephrine or norepinephrine, and 45 had secreting pheochromocytomas. In these latter patients, there were 4 false negative [131I]metaiodobenzylguanidine scans, all intraadrenal tumors, and 4 false negative CT scans, 3 extraadrenal and 1 intraadrenal tumors. 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 CT. The limits of scintigraphy are the possibility of false negative scans in around 10% of patients, whereas CT visualizes more than 95% of intraadrenal tumors.

3-Iodobenzylguanidine↗

[Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma. Experimental animal studies with 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125].

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. The transplanted tumors corresponded to the human cancers concerning histology, grading, immunohistochemistry and secretion of tumor-associated antigens. 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. These antigens are found in the serum of more than 90% of patients with pancreatic carcinoma at the time of first diagnosis. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden, as shown by experiments in 8 mice bearing 4 different human pancreatic carcinomas, 3 with positive and 1 with negative affinity to CA 19-9: the tumor retentions and the effective half-lives of 131I-anti-CA 19-9 were measured after intratumoral (100 microCi/mg tumor) or intravenous (30 and 190 microCi/g body weight) application.

Animals↗

[Localization of pheochromocytomas by scintigraphy with meta-iodobenzyl guanidine. Comparison with computed x-ray tomography].

Meta-iodobenzylguanidine was synthesized, radiolabelled with I 131 or I 123 and injected to 28 controls and 7 patients totalling 13 foci of pheochromocytoma. The tumour was located in one adrenal gland in 3 cases, in both adrenal glands in 1 case, and between the aorta and the vena cava in 1 case; 2 were malignant with metastases. Scintigraphy was negative in all controls, whereas all pheochromocytomas were clearly demonstrated 24 h after injection, except one regarded as non functional due to necrosis. By comparison, CT readily showed the tumour in 7 cases, showed it only thanks to scintigraphic guidance in 4 cases and failed in 2 cases. It is concluded that scintigraphy with meta-iodobenzylguanidine provides a safe and reliable means of locating a wide range of pheochromocytomas.

3-Iodobenzylguanidine↗

Immunoscintigraphy of colon carcinoma.

Two I-131 labeled monoclonal antibodies that react specifically with human gastrointestinal cancers in cell cultures were administered to 90 cancer patients for the scintigraphic detection of cancer sites. Antibody 17-1A, or its F(ab')2 fragments, accumulated significantly in 27 of 46 (59%) colorectal cancer sites, but not in 21 nonepitheliomatous colon cancers and cancers at other sites. Antibody 19-9, or its F(ab')2 fragments, showed significant accumulation in 19 out of 29 (66%) colorectal cancer sites. In 17 patients, immunoscintigraphy with antibody 19-9 correlated with an immunoperoxidase study with the same antibody on resected tissue specimens. In 12 patients injected with two antibodies (17-1A + 19-9, or anti-CEA + 19-9), ten of 13 colorectal cancer sites were positive.

Adult↗

Radioimmunoassay of the CA 12 5 antigen in ovarian carcinomas: advantages compared with CA 19-9 and CEA.

Antigen CA 12 5, associated with ovarian carcinomas, was assayed in the serum by an immunoradiometric method using monoclonal antibody OC 125. In a control group of 67 women in apparent good health, CA 12 5 serum levels in 64 cases (96%) were lower than 35 U/ml, the value arbitrarily considered as the upper normal limit. Using this limit, in benign lesions excluding cirrhosis, 19% (5/27) had raised levels. None of 10 cases with benign ovarian lesions had elevated values. However, in cirrhosis 86% of cases were positive being very high in 43% of cases (greater than 500 U/ml). In 38 cases of ovarian carcinomas, the overall positivity was 92% (35/38); in serous carcinomas it was 96% (26/27). For other non-ovarian cancers, particularly colonic and mammary adenocarcinomas at advanced stages, the positive rate was 43% (19/44). Finally, for 20 patients treated by chemotherapy for ovarian carcinomas and followed up by repeated CA 12 5 assays over a 2 to 8 month period, an increase or decrease in CA 12 5 levels correlated with progression or regression of the disease in 18 cases (90%).

Antibodies, Monoclonal↗

Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.

A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorectal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma patients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumulation of antibody by external photoscanning and tomoscintigraphy, whereas none of the 20 sites of other cancer types gave positive results. One-third of the patients received F(ab')2 fragments of the MAb, which gave a slightly higher percentage (61%) of positive results than did intact MAbs (51%). A few patients scheduled for tumor resection were given injections simultaneously of 131I-labeled MAb and 125I-labeled normal immunoglobulin G. Antibody concentration in resected tumors was 3.6 to 6.3 times higher than the average antibody concentration in adjacent normal tissues (1.5, 3.4, and 9.4 as compared with normal mucosa, serosa, and fat, respectively), and the specificity indices, calculated by differential radioactivity analysis, ranged from 2.1 to 5.1. The results show the potential value and limitations of this particular MAb for tumor detection by immunoscintigraphy.

Antibodies, Monoclonal↗

[Complications of appendicitis and appendectomies. Apropos of 106 cases].

Analysis of 106 case-reports of patients developing complications after appendicectomy provided data on factors predisposing to these sequelae (general condition, initial appendicitis) and their severity (26 deaths equivalent to 24,5 p. cent). Complications were exclusively medical in 22 patients (12 deaths), or surgical in 48 cases (no deaths), and were multiple and/or mixed surgical sequelae in 36 patients (14 deaths). The severity of these medical and surgical complications is emphasized and their appropriate treatment proposed. Statistical analysis of findings in patients with several complications enabled definition of risk factors: peritonitis, septic shock, renal or respiratory insufficiency, age over 50 years, and previous history of disease. Analysis of these risk factors, whether multiple or associated with other complications, can be used for numerical rating of prognosis in these patients.

Abscess↗

[Use of radio-labelled monoclonal antibodies for the scintigraphic detection of human colorectal cancers].

Two monoclonal antibodies, 17-1A and 19-9, which recognized human gastrointestinal cancers in cell cultures, were labeled with iodine 131 for immunoscintigraphic application. With the intact 131I-17-1A antibody, 21 out of 35 (60%) primary or secondary colorectal cancer sites were visualized, whereas all 21 nonepitheliomatous colic cancer sites or noncolic cancer sites were negative. With F(ab')2 fragments of the 19-9 antibody, 18 out of 27 (67%) colorectal cancer sites were positive. With both radioantibodies, the best contrasted tumor images were late, 4 to 5 days after injection. A study with paired-label technique, associating a specific iodine-131-labeled antibody with a nonspecific iodine-125-labeled immunoglobulin, demonstrated, that tumor uptake was indeed specific for the 17-1A or 19-9 antibody in tumor and normal colon fragments obtained during operations on 4 patients. A preliminary prospective study showed that only immunoscintigraphy was able to confirm and localize a recurrence of rectal cancer in one patient. A larger series will be necessary to validate the clinical benefit of the technique, as compared with the results of other diagnostic techniques, before immunoscintigraphy can be proposed for routine clinical use.

Antibodies, Monoclonal↗