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Biomedical subjects

G L Buraggi

Publications and source records attributed to G L Buraggi.

At least 37 records · Page 2Linked to original sources

Radioimmunodetection of malignant melanoma with the 225.28S monoclonal antibody to HMW-MAA.

A review of the studies on the use of the antigen-antibody system HMW-MAA 225.28S in melanoma radioimmunodetection is reported. The results obtained in a pilot study (42 patients with 74 lesions), a multicenter trial (254 patients with 553 lesions) and a prospective study still outstanding (29 patients with 38 lesions) allow to consider this system as suitable for clinical application. F(ab')2 labelled with 99mTc gave the best results in terms of positivity. Moreover this radioisotope allows the best dosimetric conditions. The gamma energy emitted by this radionuclide is particularly convenient for conventional scintillation cameras and ECT. Very good results in terms of sensitivity (70%-85%) and especially specificity (about 100%) were achieved. Possible clinical applications of the method are discussed.

Antibodies, Monoclonal↗

Adriamycin and epirubicin treatment monitored by radionuclide ejection fraction during therapy and follow-up.

Twenty-four patients with advanced breast cancer were studied with serial determinations of the radionuclide ejection fraction at rest (RST-LVEF) during anthracycline chemotherapy (CT) and with a mean follow-up (FU) of 8 months. We had 2 cases of anthracycline congestive heart failure (CHF) during FU, 3 and 12 months respectively after the end of CT. The RST-LVEF changes observed during CT were not able to predict which patients were to develop a symptomatic cardiomyopathy. The type of RST-LVEF change that is generally considered a worsening of cardiac performance is a decline greater than or equal to 15%. We had this type of RST-LVEF change, in addition to the 2 CHF, in 5 other patients without symptomatic cardiomyopathy. Nevertheless none of these 5 patients attained pathological values of RST-LVEF, while the 2 CHF showed symptomatic cardiomyopathy only when RST-LVEF became clearly pathologic (less than or equal to 46%). Therefore, although in our study the RST-LVEF changes during CT did not have predictive value for CHF, the method may give a notable clinical contribution all the same. In fact, by submitting the patients with a RST-LVEF fall greater than or equal to 15% to frequent sequential RST-LVEF determinations and stopping the CT if the RST-LVEF becomes pathologic it is possible to avoid severe and irreversible CHF.

Adult↗

Imaging with 131I-labeled monoclonal antibodies to a high-molecular-weight melanoma-associated antigen in patients with melanoma: efficacy of whole immunoglobulin and its F(ab')2 fragments.

In vitro experiments selected optimal conditions to radiolabel with 131I the whole immunoglobulin and F(ab')2 fragments of the monoclonal antibody (MoAb) 225.28S to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Injection of the radiolabeled whole immunoglobulin and F(ab')2 fragments of the MoAb 225.28S into eight patients with melanoma resulted in the accumulation of radioactivity in 10 of 18 metastases. This localization is specific because of the close relationship between detection of HMW-MAA in lesions by immunohistochemical techniques and outcome of immunoscintigraphy and because of the different distribution in tumors and adjacent tissues of radiolabeled F(ab')2 fragments of MoAb 225.28S compared with 99mTc-pertechnetate and with radiolabeled F(ab')2 fragments of MoAb 4C4 to hepatitis B surface antigen. F(ab')2 fragments are superior to whole immunoglobulins to perform immunoscintigraphy, since they markedly reduce the background in bone marrow, liver, and spleen. The sensitivity of the procedure allows the detection of lesions with a diameter of at least 1.5 cm and is influenced by the level of the HMW-MAA in lesions and by their anatomical site.

Adult↗

Tumor radioimmunolocalization in a murine system using monoclonal antibodies.

Tumor localization was obtained in a murine system by use of 131I-labeled monoclonal antibodies, both of IgG and IgM class. The A6 IgG2 monoclonal antibody (which recognizes the gp70 of MuLV) and the B3 IgM monoclonal antibody (which recognizes a proteic structure widely exposed on chemically induced tumors), which both manifest an in vitro cytotoxic activity for various types of murine lymphomas, were injected in tumor-bearing (B6 X BALB/c)F1 mice and B6 mice, respectively, at the dose of 1 microgram per mouse. The radioactivity count demonstrated an optimal tumor accumulation of the radiolabeled monoclonal antibodies 96 h after iodine injection, although an initial accumulation was already present 48 h after injection. The scanning detection was less sensitive, since at 48 h no tumor localization was possible. In the experiments with the A6 antibody, the presence of the gp70 in the circulating form, demonstrated by the detection of immunocomplexes in kidney and spleen of tumor-bearing mice injected with the A6, did not prevent radioactivity accumulation in the tumor. This accumulation was found to increase with tumor size only up to 1 g of tumor weight, then a decreased binding index was observed, whereas in the kidney the accumulation was progressive and paralleled the increase in tumor weight.

Animals↗

Studies of terminal deoxynucleotidyl transferase in normal and neoplastic human cells.

Optimized biochemical assays and cytoimmunofluorescence tests were used to detect terminal deoxynucleotidyl transferase, TdT, in malignant cells of 36 leukemias and 75 lymphomas from patients not receiving chemotherapy. TdT was virtually absent from normal lymph nodes and from leukocytes of chronic lymphocytic leukemia, CLL, taken as controls. Its quantitative distribution in the neoplasms matched the current knowledge. Appreciable amounts of TdT were found in all the 10 lymphomas of lymphoblastic type, LL, and in the white blood cells of: 16 out of 19 acute lymphoblastic leukemia, AAL, perhaps with modulation in the various phenotypes; 2 out of 3 acute undifferentiated leukemias, AUL; and 3 out of 7 blastic crises in chronic myelogenous leukemia, b.c. CML. Biochemical and cytoimmunological analyses yielded concordant responses and even roughly comparable estimates in the same patients. TdT immunofluorescence was clearly nuclear in most cells and was cytoplasmic occasionally. Definite correlations between concentrations of enzymatic activity and percentage of immunofluorescent cells could not e established. Further detailed work will be required to identify putative subgroups in TdT-positive blast populations.

Animals↗

Association of CEA test and liver scan in detection of hepatic metastases of gastrointestinal carcinoma.

The authors evaluate the combined use of liver scan and the CEA test in the diagnosis of hepatic metastases of carcinoma of the gastrointestinal tract. Association of the two tests is justified by the fact that the liver scan is very specific but not very sensitive, whereas the CEA test is more sensitive and not very specific. The sensitivity of the CEA test, on the other hand, can be increased by increasing the threshold of normality. However, the associated diagnostic use of the liver scan and the CEA test gives a loss of specificity with respect to the use of the liver scan alone. The present study, carried out on a series of 376 patients affected by gastrointestinal tumors of which 79 were of the stomach (9 with hepatic metastases), 133 of the colon and higher sigmoid (25 with hepatic metastases), and 164 of the lower sigmoid and rectum (29 with hepatic metastases), proposed to establish by use of a statistical method the optimal threshold of the CEA test that would give the best diagnostic specificity of the combined CEA test and liver scan without any relevant loss of sensitivity. A threshold of 26 ng/ml of the CEA test and gave a specificity of 92%, a sensitivity of 80%, and an accuracy of 90%. The authors think that in the detection of liver metastases of gastrointestinal tumors, the combined test can be more helpful the less the probability, for a given patient, for other metastatic localizations.

Carcinoembryonic Antigen↗

Microsphere angiography in hepatic artery infusion for cancer.

99mTc-human albumin microspheres were injected at a slow rate into the hepatic arteries of 24 patients before starting intraarterial chemotherapy for liver cancer. The distribution patterns of radiolabeled microspheres were significantly different from those obtained in contrast angiography in 13 of 22 patients. Liver uptake of slowly injected microspheres was greater than 75% in 16 of 24 patients and less than 25% in 4 of 24 patients. A significantly increased arterial blood supply to intrahepatic neoplastic regions was demonstrated in 12 of 20 patients. Microsphere examination allowed an easy evaluation of the relative perfusion of the liver and of the intrahepatic distribution of arterial blood flow in all patients.

Angiography↗

[Cyclic AMP levels of peripheral lymphocytes in normal subjects and in patients with malignant neoplasms].

Cellular cAMP was determined by the competitive protein binding assay (RIA method) in peripheral blood lymphocytes (PBL) isolated from 34 healthy blood donors and 31 tumor bearing patients. cAMP concentration in PBL from the cancerous patients was lower than the one found in healthy blood donors. Results are discussed in relation to the modification of immune reactivity induced by cancer.

Breast Neoplasms↗

Double-tracer scintigraphy with 67Ga-citrate and 99mTc-sulfur colloid in the diagnosis of hepatic tumors.

A method of liver scanning based on a subtraction technique with simultaneous use of two tracers, 67Ga-citrate and 99mTc-sulfur colloid, is described. The subtraction technique isolates radiogallium uptake by the space-occupying hepatic lesions by subtracting interference due to tracer uptake by healthy hepatic tissue. In 82 patients, the method yielded a correct result in 94.7% of the positive scans and in 97.7% of the negatives. Two false positives and one false negative occurred. Very poor results were obtained in the same patients using conventional technetium and gallium scans: only 20.7% of these interpretations were correct. The method proved very helpful in differentiating malignant from benign lesions.

Carcinoma, Hepatocellular↗