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Biomedical subjects

A C Perkins

Publications and source records attributed to A C Perkins.

At least 127 records · Page 7Linked to original sources
PubMed1988

Imaging of pancreatic and colorectal cancer using antibody fragments: a preliminary evaluation.

Imacis-1 is a combination of F (ab')2 antibody fragments, of two monoclonal antibodies, anti-CEA and 19.9, radiolabelled with Iodine-131. Thirteen patients with 14 tumours (eight pancreatic, six colorectal) were imaged to evaluate the ability of this radiopharmaceutical to detect both pancreatic and colorectal cancer. Positive tumour uptake was demonstrated by external gamma camera imaging in six patients with pancreatic cancer and in three with colorectal cancer. The results of this preliminary study confirm the ability of this antibody cocktail to localise in colorectal cancer and suggest that it may be of value in the detection of pancreatic cancer.

Antibodies, Monoclonal↗
PubMed1988

The implications of patient antibody response for the clinical usefulness of immunoscintigraphy.

The evolving clinical role for tumour immunoscintigraphy appears to be in monitoring patients for metastatic spread and tumour recurrence. Such diagnostic strategies inevitably involve repeat imaging investigations, and therefore the probability of patient immunization against the administered radiopharmaceutical is increased. Patient antibody responses would appear to affect the quality and sensitivity of repeat imaging studies, and this also has implications for the therapeutic efficacy of subsequent therapy doses. A simple test for determining patient sensitization to antibody is required.

Antibodies, Monoclonal↗
PubMed1987

Diverse characteristics of 111In labelled anti-CEA monoclonal antibodies for tumour immunoscintigraphy: radiolabelling, biodistribution and imaging studies in mice with human tumour xenografts.

Three monoclonal anti-CEA antibodies, designated 161, 198 (both IgG1) and 228 (IgG2a) have been labelled with 111In via DTPA chelation and assessed for localization in human gastro-intestinal carcinomas as xenografts in athymic nude mice. Following reaction of the antibodies with DTPA anhydride, efficiency of chelation of 111In varied between the antibodies with mean values of 30%, 52% and 62% with 161, 198 and 228 respectively. Gel filtration chromatography with all three labelled antibodies showed radiolabel predominantly coincident with IgG with little radioactivity in either high molecular weight form or as free 111In. However, the efficiency of binding of radiolabelled antibodies to CEA producing tumour cells varied, with maxima of 42%, 65% and 20% for 161, 198 and 228. In vivo, in mice, 111In was excreted at virtually identical rates (half times approx. 12 days) with all three preparations and this was similar to the clearance of indium injected as 111In-indium chloride, but 111In-DTPA was rapidly eliminated (half time approximately 5 h). After injection into mice with CEA producing xenografts of colon carcinoma HT29 and LS174T and gastric carcinoma MKN 45, circulating radiolabel was still predominantly in the form of labelled antibody with little or no detectable immune complexes or 111In labelled transferrin. Tumour localization of all three antibodies was visualized by gamma camera imaging with target: non target ratios of up to 5:1. Dissection of mice with MKN45 gastric carcinoma xenograft showed 16%, 19.5% and 13% of the injected dose of 111In from 161, 198 and 228 antibodies in each g of tumour tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Diagnostic imaging of gynecologic tumors with the monoclonal antibody 791T/36.

One hundred twenty-three patients with suspected primary or recurrent gynecologic cancer were imaged after infusion with radiolabeled antitumor monoclonal antibody (791T/36). Overall sensitivity of tumor detection was 87% and specificity was 75%. Indium 111- and iodine 131-labeled antibody were compared, the former yielding a higher specificity for tumor detection. This antibody shows potential for routine tumor detection, particularly in cases of suspected recurrent cancer, but the development of antimouse antibodies is a drawback to this technique still to be overcome. The specific targeting of cytotoxic agents with this antibody is in progress.

Antibodies, Monoclonal↗
PubMed1987

Reliability of the hepatic perfusion index for the detection of liver metastases.

The reliability of the technique for measuring the hepatic perfusion index (HPI) for the detection of liver metastases has been examined. Dynamic images from 173 patients with primary and recurrent colorectal cancer have been analysed by two operators using the peak values of both the right and left kidney time-activity curves. In 14.4% of analyses the right kidney HPI method failed, while only 5.7% of analyses failed using the left kidney method. The results showed (a) that disagreement between the operators HPI values was small but statistically significant (p less than 0.05) and (b) that disagreement between the two methods was highly significant (p less than 10(-7)), with the left kidney method resulting in a lower HPI value. An upper limit of normal for left kidney HPI of 0.37 was predicted from the data, assuming the corresponding right kidney value to be 0.40.

Evaluation Studies as Topic↗
PubMed1987

Imaging of primary and metastatic colorectal carcinoma with monoclonal antibody 791T/36 and the therapeutic potential of antibody-drug conjugates.

Monoclonal antibody 791T/36, prepared against a tumour-associated 72,000 dalton glycoprotein, reacted with cells from primary and metastatic colorectal carcinomas. I-131 or In-111-labelled antibody localized in xenografts of colorectal carcinomas established from in vitro clonogenic populations. Clinically, with I-131-labelled antibody, 8/11 colonic tumours imaged positively. Imaging was negative in four patients with benign colon disease. 5/11 rectal tumours were positively imaged, but excreted I-131 in the bladder obscured tumours in several studies. In-111-labelled antibody gave superior images and positively imaged primary and metastatic sites in 13/14 patients. Prospectively in the detection of recurrent disease, I-131 or In-111-antibody detected 29/33 separate sites in 24 patients. Seven negative patients remain disease free. There were 3 false positives; overall sensitivity was 88%, with 70% specificity. Specific localization of radiolabel was confirmed immunochemically and by counting radioactivity in resected specimens. Antibody conjugates with methotrexate, vindesine and daunomycin retained drug activity and antibody function, including xenograft localization and conjugates were therapeutically effective against xenografts. 791T/36 antibody has potential for immunodetection of primary and recurrent colorectal carcinoma and for targeting of therapeutic agents.

Animals↗
PubMed1986

Imaging of bone tumors using a monoclonal antibody raised against human osteosarcoma.

The radiolabeled monoclonal antibody 791T/36 raised against a human osteosarcoma was injected into 20 patients with known or suspected bone tumors. Gamma camera images were acquired at 48 or 72 hours after injection, and assessed for antibody localization. Positive images were obtained in all five osteosarcomas and four other primary malignant sarcomas. Two of the four other primary bone tumors gave positive images. Three patients with trauma had negative images as did one patient with Paget's disease. Two patients with suppurative disease gave positive images. The antibody localized in the majority of malignant sarcomas tested. In one tumor where tissue was available, a tumor:non-tumor ratio of 2.8:1 was measured. Repeat imaging was performed in five patients. Immunoscintigraphy using the monoclonal antibody 791T/36 has shown tumor localization in patients with bone and soft tissue sarcomas.

Adolescent↗
PubMed1986

In vitro binding and in vivo localization in colorectal cancer of a high affinity monoclonal antibody to carcinoembryonic antigen.

A monoclonal antibody to carcinoembryonic antigen (CEA) (C46) was tested for its binding properties to colorectal cancer cells in vitro and for its localization in patients with primary colorectal cancer. Strong binding was found to disaggregated primary colorectal cancer cells, with a median of 66 per cent of the cells in the tumour gate binding the antibody. There was a median binding ratio of 8.6:1 compared with normal immunoglobulin. The pattern of immunohistological staining was typical of that for an antibody to CEA. All seven patients with primary colorectal cancer imaged pre-operatively using 111In-labelled C46 gave positive images. The median tumour:non-tumour antibody uptake ratio from resected specimens (n = 8) was 5.8:1. (1.7-7.6:1). Eight of 11 sites of secondary colorectal cancer gave positive images. The high affinity and good tumour localization of C46 have improved clinical imaging and increase the possibilities for targetting of antitumour agents.

Aged↗
PubMed1986

Comparative imaging and biodistribution studies with an anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments in mice with colon carcinoma xenografts.

An IgG1 mouse monoclonal antibody directed against CEA has been digested with papain to yield F(ab)2 and Fab fragments. Following radioiodination, intact antibody and fragments showed specific binding to cells of a CEA-producing tumour, although the immune reactivities of the fragments were lower than that of intact antibody. Gamma scintigraphy of nude mice bearing CEA-producing human tumour xenografts and injected with 131I-labelled fragments showed earlier and superior imaging of tumours than did 131I-intact antibody, and this was most marked with the Fab fragment. Sequential dissection analyses showed that this was due to earlier and higher tumour-to-blood ratios with fragments than with intact antibody, but in absolute terms the degree of localization of both fragment types was significantly lower than that of intact antibody.

Adenocarcinoma↗
PubMed1986

Antigenicity of newly established colorectal carcinoma cell lines.

Cells from two adenocarcinomas, an adenoma and a metastatic node were isolated in soft agar. Expression of antigens, CEA, Y haptenic blood group and 791T-p72, defined by a range of candidate antibodies for tumour targeting was assessed. All of the cells expressed low levels of CEA but high levels of the Y haptenic blood group antigen although there was enormous inter and intraclonal variation. Of particular interest was the membrane expression of 791T-p72 antigen on all of the dividing tumour cells as previous studies had shown that 791T/36 antibody reacted with tumour stromal elements rather than malignant cell surfaces. The DNA content was abnormal in all of the cells whether they were derived from diploid or aneuploid primary tumours. They all grew readily in athymic mice and at least one monoclonal antibody, 791T/36, localised efficiently within these xenografts. Clonogenic cells therefore expressed the three tumour-associated antigens, several at higher levels than observed in the primary tumour. Monoclonal antibody 'cocktails' should therefore allow antibody mediated drug cytotoxicity to be effective at eradicating rapidly dividing tumour cells.

Adenocarcinoma↗
PubMed1986

131I and 111In-labelled monoclonal antibody imaging of primary lung carcinoma.

Preliminary clinical studies have been carried out to determine whether the monoclonal antibody 791T/36 would localize in primary lung cancer to an extent sufficient for external detection by gamma scintigraphy. Radiolabelling of the antibody with 131I permitted visualization of three out of eight (38%) tumours using planar imaging with 99Tcm-labelled blood pool subtraction. Radiolabelling of the same antibody with 111In permitted visualization of tumour uptake in nine out of 13 (69%) tumours, without the need for image subtraction. Single photon emission computed tomography (SPECT) studies of seven patients demonstrated concentration of 111In-labelled antibody at the tumour site in each case, four of which were visualized on the planar images. The present study demonstrates localization of the 791T/36 antibody in primary lung carcinoma and confirms the superiority of 111In over 131I as a radiolabel for antibody imaging, especially when emission tomography is performed. These data indicate that further work will be required to determine whether this antibody will be a suitable carrier for cytotoxic agents in the therapy of lung cancer.

Aged↗
PubMed1985

Localization of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts.

A mouse monoclonal anti-CEA antibody (11.285.14) has been examined for tumour localization potential by assessing its distribution in immunodeprived mice with xenografts of human colon carcinoma cell lines HCT-8, HRT-18, HT-29, and LS174T and a xenograft (HRVB) established from a primary rectal carcinoma. With four carcinomas (HCT-8, HT-29, LS174T, and HRVB) preferential tumour localization of 125I anti-CEA was seen. Compared with 131I normal IgG1 localization indices of up to 4.4:1 were achieved. Up to 10% of the injected dose of 125I anti-CEA was present/g of tumour tissue and with the largest xenografts examined (3-4 g) up to 40% of the total body reactivity was localized in tumour tissue. The tumour localization of 131I labelled antibody was visualized by external gamma camera imaging. Overall antibody localization correlated with the CEA content of the xenografts and the fourth colon carcinoma xenograft (HRT-18) and an osteogenic sarcoma xenograft (791T), both with very low CEA levels, showed no localization of the monoclonal antibody.

Animals↗
PubMed1985

Localization of anti-osteogenic sarcoma monoclonal antibody 791T/36 in a primary human osteogenic sarcoma and its subsequent xenograft in immunodeprived mice.

A primary human osteogenic sarcoma was visualized in situ by external gamma-camera imaging following administration of 131I-labelled anti-osteogenic sarcoma monoclonal antibody 791T/36. A xenograft of the tumour established in immunodeprived mice also showed localization of 131I-791T/36 determined by both gamma-camera imaging and organ distribution studies. Radiolabelled normal immunoglobulin showed no tumour localization. Expression of the 791T/36-defined antigen on xenografted tissue was further confirmed by reaction of its in vitro-cultured cells with fluorescein-labelled 791T/36 antibody.

Animals↗
PubMed1985

The preparation and characterisation of 111In-labelled 791T/36 monoclonal antibody for tumour immunoscintigraphy.

The anti-human tumour monoclonal antibody 791T/36 was conjugated to the cyclic dianhydride of DTPA and radio-labelled with 111In. The labelling method proved to be both simple and reliable and would be suitable for routine clinical use. Subsequent characterisation of this radio-pharmaceutical in vitro and in tumour-bearing hosts gave a strong indication as to its suitability for clinical tumour localisation studies.

Animals↗