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Biomedical subjects

M Granowska

Publications and source records attributed to M Granowska.

At least 55 records · Page 3Linked to original sources

Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration.

The localization of i.p. injected, radioiodine conjugated monoclonal antibody HMFG2 was studied in 18 patients with ovarian carcinoma. Patients were injected i.p. at time points up to 168 h before laparotomy, at which time tumor, ascites, normal tissue, and blood samples were removed and the contained radioactivity measured. In the first 10 patients, localization was compared with that of a simultaneously injected irrelevant (nonspecific) antibody (UJ13A) of the same immunoglobulin class and, in the subsequent 8 patients, with HMFG2 administered i.v. After i.p. injection, HMFG2-radioiodine was found in concentrations of 0.0001-0.0030% of the injected amount per gram in solid tumor, 0.0363-0.02560%/g in ascites, 0.0003-0.0017%/g in blood, and 0.001-0.0012%/g in normal tissue. Tumor:normal tissue ratios of 0.9-10.0 and tumor:blood ratios of 0.3-4.0 were seen up to 168 h after injection. Localization of the HMFG2 conjugate was consistently greater than that of the irrelevant antibody. For solid tumor, the i.v. route of administration resulted in consistently higher absolute levels of HMFG2 conjugate uptake but tumor:blood and tumor:normal tissue ratios were similar. On the other hand the i.p. route of administration offered consistent advantages of 4- to 71-fold over the i.v. route when HMFG2 conjugate localization on ascites cells was examined. Ascites:normal tissue and ascites:blood ratios of up to 512 and 448, respectively, were achieved. After i.p. injection, radioiodine was cleared from the body exponentially with a half-life of 50 h. Maximum circulating blood levels of 8.6 +/- 2.0% injected activity were seen at 48 h and these then decreased with a t 1/2 value of 38 h. Over 80% of injected activity was cleared in the urine as nonprotein bound iodine by 168 h.

Antibodies, Monoclonal↗

Tumour-associated monoclonal antibodies for the diagnosis and assessment of ovarian cancer.

A tumour-associated radiolabelled monoclonal antibody (HMFG 2) was used to investigate 51 patients who were referred with a pelvic mass and suspected ovarian cancer or recurrent disease. The day before operation the 123I-labelled antibody was injected and the patients then underwent radioimmunoscintigraphy immediately and again 4 and 22 h after the injection. An exploratory laparotomy with appropriate surgery was then performed and the tumours were staged. Tumours were positively imaged 3 min-22 h after injection in all the patients with ovarian cancer, with a mean 0.6% of the injected antibody taken up by the tumour. The presence of HMFG antigen on the tumour was confirmed by immunoperoxidase staining of the surgically-removed tissues. Of the 51 patients, 39 proved to have ovarian cancer. The accuracy of diagnosis and detection of primary and metastatic malignant disease was 95% when correlating pre-operative radioimmune scan findings and laparotomy findings. The procedure is minimally invasive, apparently without side-effects and offers information for tumour detection as an adjunct or alternative to existing methods.

Antibodies, Monoclonal↗

Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Antibodies, Monoclonal↗

Radioimmunoscintigraphy of ocular melanoma with 99mTc labelled cutaneous melanoma antibody fragments.

The possibility of using radiolabelled monoclonal antibody fragments to image uveal melanomas has been assessed in a pilot study. 99mTc labelled F(ab')2 fragments of MoAb 225.28S raised against cutaneous melanomas were used. Initially 10 patients were imaged. In five patients the clinical findings were typical of uveal melanoma. Immunoscintigraphy was positive in all five cases. In a further five patients there was doubt about the diagnosis. One was though to have a choroidal haemangioma but failed to respond to treatment and immunoscintigraphy was positive, suggesting a diagnosis of melanoma. Two patients were assigned a diagnosis of choroidal haemangioma, one of melanocytoma or possible retinal pigment epithelium carcinoma, and one of metastasis. Immunoscintigraphy was negative in all these four cases. In combination with established diagnostic tests immunoscintigraphy may have a part to play in differentiating uveal melanoma from other similar tumours.

Adult↗

Total and intrarenal flow distribution in healthy subjects: technique, acute effects of ibopamine and of indoramin.

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of 123I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, and alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated although there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

Adult↗

A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.

Antibodies, Monoclonal↗

123I radioiodinated antibody imaging of occult ovarian cancer.

A monoclonal antibody HMFG2 labeled with iodine 123 (123I) was given to a patient who had ovarian cancer. The scan taken 18 hours after administration of the antibody demonstrated the presence and the position of residual tumor in the pelvis that was not previously detected by ultrasonography and computerized tomography (CT) scanning. The presence of tumor was confirmed by surgery and histologic as well as immunoperoxidase examination of resected tissues. The tumor mass found was less than 0.8 cm in diameter. It is concluded that, in the search for residual or early ovarian cancer in the pelvis, monoclonal antibody scanning using 123I-labeled HMFG2 can complement ultrasonography and CT scanning.

Adenocarcinoma↗

Cerebral blood flow in hypertensive patients with cerebrovascular disease: technique for measurement and effect of captopril.

Nineteen patients with unilateral cerebrovascular disease underwent cerebral blood flow (CBF) measurements; ten had been receiving conventional therapy and then were studied after treatment with captopril without or with a diuretic and nine on conventional therapy were studied twice as a control group. CBF (ml min-1) was measured after an intravenous injection of 99Tcm-labelled patient's red cells with a computer linked gamma camera over the vertex and a probe over the aorta. With deconvolution analysis regional CBF is given by regional cerebral volume divided by regional mean transit time. Results in the captopril group showed on average a 10% fall in mean blood pressure and a 10% rise in blood flow to the affected hemisphere. In the control group there was on average a 4% fall in pressure, together with an 11% fall in CBF to the affected hemisphere. Captopril appears to maintain autoregulation in cerebrovascular disease.

Adult↗

Radioimmunodiagnosis of ovarian cancer using 123I-labelled, tumor-associated monoclonal antibodies.

Monoclonal antibodies to epithelial cells, antigenic determinants labelled with I123 and I125, were administered to 10 immunodeficient mice bearing subcutaneous xenografts of human ovarian cancer. Radio scans of the body taken with a gamma camera at various time intervals demonstrated the presence of the cancer in all the mice. The smallest detectable tumor was approximately 1 mm in diameter. In a subsequent clinical study using 123I-labelled monoclonal antibodies in 10 patients with ovarian cancer, tumor detection was achieved in 8 patients, with tumor uptake of labelled antibody ranging between 0.2-2.6%. As a complementary method to existing forms of diagnosis, the targeting of monoclonal antibodies to ovarian cancer cells in vivo raises the hope of achieving early diagnosis in otherwise undetectable ovarian cancer, and provides encouragement to the concept of selective therapy in oncology.

Adenocarcinoma↗

Monoclonal antibodies for successful tumour imaging.

The monoclonal antibody HMFG-2 which is directed to an oligosaccharide determinant on a large molecular weight mucin-like molecule found in the human milk fat globule reacts positively with breast and ovarian carcinomas. The purified antibody, labelled with 123I has been used successfully to locate ovarian tumours and their metastases in 20 out of 22 patients tested. Here we discuss those features of a) the antibody, b) the antigenic site it reacts with, c) the radioactive label and d) the scanning technique, which have contributed to the successful application of HMFG-2 to the effective imaging of ovarian tumours.

Antibodies, Monoclonal↗