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A C Perkins

Publications and source records attributed to A C Perkins.

At least 145 records · Page 8Linked to original sources

Differences in tumour and normal tissue concentrations of iodine- and indium-labelled monoclonal antibody. I. The effect on image contrast in clinical studies.

The poor imaging characteristics of 131I have resulted in the use of alternative radionuclides for radiolabelling monoclonal antibodies. Clinical imaging studies have shown that, in addition to the more suitable energy of emission of 111In over 131I for gamma camera detection, the 111In-labelled antibody appears to clear from the bloodstream at a faster rate than that of 131I-labelled antibody, resulting in greater tumour-to-background image contrast. However, measurements of the activity in blood samples from patients demonstrate that both 131I- and 111In-labelled antibodies clear from the circulation at similar rates. This discrepancy is probably due to the different biological fates of the two radionuclides and warrants further scientific study.

Antibodies, Monoclonal↗

Differences in tumour and normal tissue concentrations of iodine- and indium-labelled monoclonal antibody. II. Biodistribution studies in mice with human tumour xenografts.

The blood, tumour and whole-body levels and survivals of 131I- and 111In-labelled monoclonal antibody (791T/36) have been compared in mice with human tumour xenografts. The blood levels and survivals of 131I- and 111In-labelled antibody were similar when expressed as proportions of the injected doses. However, the whole-body survival of 111In following administration of 111In-labelled antibody was over twice as long as that of 131I after administration of 131I-labelled antibody, principally because free 131I was rapidly excreted but free 111In was retained, primarily in liver, spleen and kidneys. Consequently, when expressed in relation to the whole body, blood levels of 111In became progressively lower than those of 131I following administration of labelled antibodies. In mice with human tumour xenografts the proportion of the injected dose of 111In from 111In-labelled antibody deposited in tumour tissue was 4-5 times higher than that of 131I from 131I-labelled antibody. When compared with the whole-body levels of radiolabel the difference was less marked, although 111In accumulation in tumour was more rapid. The higher levels and longer retention of 111In in tumour produced tumour-to-blood ratios that were 7-8 times those achieved with 131I-labelled antibody.

Animals↗

Validity of the geometric mean correction in the quantification of whole bowel transit.

The accurate interpretation of gastrointestinal transit studies often requires quantification of the data. Particles radiolabelled with indium-111 have been monitored using a gamma camera, during transit through the stomach and the small and large intestines of normal subjects. The count rates measured from either anterior or posterior images alone showed considerable variations, and depended on the site of the tracer within the gut. The geometric mean values of corresponding anterior and posterior count rates remained almost constant throughout each study.

Adult↗

Imaging of primary and metastatic colorectal cancer using an 111In-labelled antitumour monoclonal antibody (791T/36).

The monoclonal antitumour antibody 791T/36, previously shown to localize in colorectal cancer when radiolabelled with 131I, has been successfully labelled with 111In. A preliminary evaluation of its imaging potential has been made in fourteen patients with primary and secondary colorectal cancer. Positive localization was achieved in tumour sites of all but one of the patients. The sites of uptake of the 111In-labelled antibody were more clearly defined than when using the same antibody labelled with 131I. The mean tumour to normal tissue uptake ratio per gram of tissue from four resected specimens was 2.8:1. Labelling of the antibody did not affect the tumour uptake of the antibody but facilitated interpretation directly from images without the need for background subtraction.

Aged↗

Clinical implications for immunoscintigraphy in patients with ovarian malignancy: a preliminary study using monoclonal antibody 791T/36.

Twelve patients with suspected primary and recurrent carcinoma of the ovary have undergone immunoscintigraphy with an antitumour monoclonal antibody in order to assess the impact of the technique on patient management. Consistent tumour uptake of radiolabelled antibody was visualized in malignant tumours after subtraction of the blood background activity. Eight patients were imaged before surgery and in all of these the sites of uptake visualized on the images agreed with the surgical findings. In one patient with recurrent disease the imaging information was used as an aid for establishing the extent of external beam radiotherapy. A repeat study in this patient 6 months later revealed a reduction in the size of the tumour, which still concentrated labelled antibody and confirmed the viability of repeat investigations. Immunoscintigraphy was capable of providing diagnostic information which may offer an alternative to second-look surgery in these patients.

Adult↗

The characteristics of blood-borne radiolabels and the effect of anti-mouse IgG antibodies on localization of radiolabeled monoclonal antibody in cancer patients.

Quantitative and qualitative aspects of the blood survival of 131I and 111In-labeled monoclonal antibody 791T/36 have been examined in patients with colo-rectal carcinoma, ovarian carcinoma and osteogenic sarcoma who were receiving labeled antibody in diagnostic immunoscintigraphy trials. The blood clearance of intact antibody radiolabeled with either 131I or 111In was similar. A bi-phasic decline of both radiolabeled preparations was measured with initial half-lives 0.62 and 0.42 days for 131I and 111In labels and then with 1.85 and 1.40 day half-lives, respectively. The Fab fragment of the antibody was lost more rapidly (initial half-life 0.20 days and then 0.78 days). Blood-borne radioactivity was associated predominantly with plasma rather than cellular elements. Radioactivity was still attached to undegraded, uncomplexed, and immunologically active antibody as demonstrated by molecular filtration, immune precipitation, and antigen binding assays. However, anti-mouse-IgG antibody detected within 7 days of administration of radiolabeled antibody was present for at least 10 mo and has implications for the efficiency of repeated image studies.

Animals↗

The localization of an anti-tumour monoclonal antibody (791T/36) in gastrointestinal tumours.

Fifty-six patients with gastrointestinal cancers and four patients with benign colorectal tumours have been injected with radiolabelled anti-tumour monoclonal antibody ( 791T /36) to assess the degree of localization of the antibody by external scintiscanning and measurements on resected specimens. Twenty-nine patients with primary colorectal cancer showed increased uptake of the radiolabelled antibody in the resected tumours, with a tumour to normal tissue (T:NT) ratio of 2.5:1. All but two of fifteen patients with recurrent or metastatic tumour showed positive images of the deposits on external scintiscanning. Twelve patients with noncolonic gastrointestinal malignancy were studied and in only two patients were tumours demonstrated by external scanning. There were no positive images in four patients with benign colonic disease nor could increased uptake of radiolabelled antibody be demonstrated in the resected specimens. Immunohistology and autoradiography have shown that the antibody can be demonstrated in the pseudoacini and stroma of colon cancer. There are indications that this may represent localization to a cell surface antigen which becomes detached in the processing of the histological sections. It seems that in the gastrointestinal tract the monoclonal antibody 791T /36 is consistently taken up by colorectal cancer. Only a few noncolonic cancers and no benign colonic tumours take up the antibody. This antibody uptake may prove of value in the detection of occult metastases and in the targeting of antitumour agents.

Aged↗

Physical approach for the reduction of dual radionuclide image subtraction artefacts in immunoscintigraphy.

Investigations have been undertaken into methods for reducing the artefacts resulting from the subtraction of images during immunoscintigraphy. The image subtraction techniques have been assessed using simple phantoms and the results applied to the image processing of clinical studies. Subtraction images were viewed for artefacts and the changes in target-to-nontarget ratios measured. Subtraction artefacts were reduced considerably using a combination of radionuclides with similar photopeak energies. In the case of 131I-labelled antibodies a blood pool subtraction with 113Inm was applied. When the images of radionuclides having very different photopeak energies were subtracted as in the case of 131I and 99Tcm, a preliminary background thresholding of the iodine image prior to 99Tcm subtraction reduced the artefacts due to the differential septal penetration and scatter components.

Antibodies, Monoclonal↗

Ultrasound in the localisation of bladder tumours for radiotherapy treatment planning.

Radiation treatment fields have been established in 40 patients with carcinoma of the urinary bladder using a technique based on B-scan measurements of tumour dimensions and position. Three-dimensional data were obtained using omnidirectional calipers and the in-built measuring system of the scanner gantry, and by measurement from the recorded images. All measurements of the tumour dimensions and co-ordinates of the tumour centre were related to a fixed patient reference point. The ultrasound measurements were superimposed on to the AP and lateral planning radiographs after multiplication by the appropriate magnification factor. Ultrasound tomograms provided accurate data for radiotherapy planning and offer a convenient method for monitoring the response to treatment on follow-up.

Humans↗

Immunoscintigraphy of tumours: possibilities and limitations.

Monoclonal antibodies to tumour-associated products offer the possibility to assess the role of immunoscintigraphy in diagnosis and management of malignant disease. Although images obtained from patients are often technically impressive the technique has yet to be proven to be of general diagnostic usefulness compared with other diagnostic methods. Further refinements, particularly in the use of antibody fragments, different radiolabels and more advanced imaging systems, particularly tomoscintigraphy, may improve the efficiency and resolution of the technique and ultimately lead to more widespread diagnostic application, although problems associated with administration of foreign immunoglobulins will have to be overcome.

Animals↗

The use of monoclonal antibody 791T/36 in the immunoscintigraphy of primary and metastatic carcinoma of the breast.

Radiolabelled monoclonal antibody 791T/36 raised against a human osteogenic sarcoma cell line was used to image primary and metastatic tumours in 13 patients with mammary carcinoma. Successful imaging was achieved in 3 of 5 women with primary tumours, in one woman with hepatic metastases, 3 with loco-regional metastases and one with pleural involvement. No localization was demonstrated at sites of known bone involvement in 5 patients.

Adult↗

Immunoscintigraphy of colorectal carcinoma with monoclonal antibody 791T/36.

A monoclonal antibody 791T/36 prepared against a human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinoma by external imaging of patients infused with 131I-labelled antibody. Positive images were obtained with 8/11 primary colon tumours, 5/12 rectal tumours and 14/15 secondary and recurrent tumours. Positive tumour localization of radiolabelled antibody was confirmed by imaging and radioactivity counts on resected specimens. None of five patients with benign colorectal disease showed positive images and only 2/12 other gastrointestinal cancers were detected.

Animals↗

Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody.

In 10 out of 11 patients with colorectal cancer radiolabelled antitumour monoclonal antibody (791T/36) was localised to the tumour. The mean tumour to non-tumour uptake ratio of antibody demonstrated by imaging with a gamma camera was 4.4/1 after subtraction of background radioactivity. The antibody did not localise in one patient who had received radiotherapy to his tumour two weeks previously. In 5 patients with primary neoplasms localisation of the antibody was confirmed by further imaging of the resected specimens and in-vitro radioactivity counting of the tumour and comparison with the activity in adjacent normal colon.

Adult↗