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Biomedical subjects

M V Pimm

Publications and source records attributed to M V Pimm.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

Quantitative evaluation of the localization of a monoclonal antibody (791T/36) in human osteogenic sarcoma xenografts.

Monoclonal antibody 791T /36 (IgG2b) directed against human osteogenic sarcoma-associated antigens has been used to examine quantitative aspects of in vivo tumour localization into osteogenic sarcoma xenografts. With small doses of antibody (less than 40 micrograms) the extent of localization consistently correlated with xenograft size, an average of 36% of the total body burden of radiolabelled antibody being present/g tumour after 2 or 3 days. Parallel studies with labelled control IgG2b showed a similar correlation, but only 7% of the total body radiolabel was localized/g tumour. With the 791T /36 antibody, the tumour: blood ratio did not increase with tumour size except with the largest xenografts (800-900 mg), where up to 30-40% of the total body radioactivity was localized within the xenografts and this was sufficient to produce a measurable decrease in its blood level. There was also a significant correlation between the dose of injected radiolabelled antibody and the amount localized in xenografts but only up to a dose of about 100 micrograms, beyond which the amount localized was not directly proportional to the injected dose. The maximum level of radiolabelled antibody localized in xenografts was 70 micrograms antibody/g tumour tissue. It was not possible to displace radiolabelled antibody already localized in xenografts by systemic administration of a large dose of unlabelled antibody. The rate of localization of antibody was such that maximum uptake, measured as the absolute amount of localized antibody, was seen 2-4 days after injection. After this time the absolute amount of antibody in the tumours declined, but not as rapidly as the blood and whole body levels, so that the tumour: blood ratio continued to increase with time.

Animals↗
PubMed1984

Liposomal encapsulation augments delayed hypersensitivity reactions to tuberculin proteins.

Encapsulation of purified tuberculoproteins in liposomes augmented their ability to elicit delayed hypersensitivity reactions in BCG-immune rats. The effect was most marked with a low-molecular-weight tuberculopeptide that was relatively poor at eliciting reactions when in free form. These findings indicate that, in addition to the antigenic nature of the material, the physical form of presentation of mycobacterial test antigens can influence their ability to elicit hypersensitivity reactions.

Animals↗
PubMed1984

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↗
PubMed1984

Tumour models for screening immunomodulators: suppression of tumour growth by delayed hypersensitivity reactions.

The suppression of tumour growth at the site of delayed type hypersensitivity (DTH) reactions has been examined with a range of three transplanted rat mammary carcinomas of spontaneous origin. Growth of subcutaneous challenge inocula was suppressed by addition of BCG organisms, but only in rats pre-sensitized to BCG. Purified protein derivative (PPD) was equally effective, but again only in BCG pre-immunized rats. The tumour suppressive response could be adoptively transferred to untreated rats with BCG-immune lymph node cells. Liposomally encapsulated PPD suppressed pulmonary tumour growth in BCG immune rats. These findings indicate the feasibility of therapeutic suppression of tumour growth by agents eliciting DTH reactions, if these can be selectively targeted to tumour sites.

Adjuvants, Immunologic↗
PubMed1984

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↗
PubMed1984

Monoclonal antitumour antibodies for tumour detection and therapy.

The potential of anti-tumour monoclonal antibodies for tumour detection and therapy are considered. Immunoscintigraphy of patients following injection of monoclonal antibodies labelled with gamma-emitting radionuclides has been successfully used to detect a range of human cancers including carcinomas of colon, breast and ovary and osteogenic sarcomas. This application of monoclonal antibodies is considered with respect to the design of imaging procedures and the clinical usefulness of the techniques. Another potentially useful application of anti-tumour monoclonal antibodies is for targeting therapeutic agents. This approach is considered particularly with respect to the use of antibodies for targeting cytotoxic drugs.

Animals↗