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PubMed1993

Radioimmunoscintigraphy with technetium-99m-labelled monoclonal antibody, SM3, in gynaecological cancer.

Radioimmunoscintigraphy (RIS) with technetium-99m labelled SM3, a monoclonal antibody reacting with a polymorphic epithelial mucin glycoprotein core antigen, is evaluated. No adverse effects or thyroid uptake were observed. Studies in 45 patients (one twice) had a sensitivity for gynaecological malignancy of 100% (35/35) and a specificity of 73% (8/11), giving an overall accuracy of 93% (43/46). These results have led to the routine adoption of 99mTc RIS in the management of patients suspected of or having primary or recurrent gynaecological cancer.

Adult↗
PubMed1993

Improved detection of a staphylococcal infection by monomeric and protein A-purified polyclonal human immunoglobulin.

The present study was undertaken to compare the technetium-99m labelled non-specific polyclonal human immunoglobulin (Ig) with 99mTc-labelled monomeric human immunoglobulin (m-Ig), 99mTc-labelled, protein A-purified, human immunoglobulin (A-Ig) and 99mTc-labelled monomeric, protein A-purified, human immunoglobulin (mA-Ig) as tracer agents for the detection of a thigh infection with Staphylococcus aureus. In vitro the binding of the various tracer agents to bacteria at various intervals was determined. For the in vivo evaluation, mice were infected and received one of the various labelled proteins. Scintigrams were made 0.25, 1, 4 and 24 h later. All 99mTc-labelled Igs bound to bacteria in vitro: the percentages of binding for the m-Ig (from 1 h onwards) and A-Ig and mA-Ig (from 3 h onwards) were significantly higher than that for Ig. The in vivo target-to-non-target (T/NT) ratios were significantly higher from 4 h onwards for all purified Igs than for Ig. Protein A-purified Igs yielded higher T/NT ratios than m-Ig. Furthermore, the amount of activity in the liver was significantly lower 24 h after administration of m-Ig, A-Ig and mA-Ig than after administration of Ig. It is concluded that in this experimental infection 99mTc-labelled monomeric Ig localizes a staphylococcal thigh infection better and faster than 99mTc-labelled unpurified Ig. However, the accumulation obtained with protein A-purified Ig or protein A-purified monomeric Ig was the highest of all tracer agents tested.

Animals↗
PubMed1993

Localization of hepatic metastases by radiolabelled anti-carcinoembryonic antigen antibody and meta-iodobenzylguanidine in a patient with medullary thyroid carcinoma.

Sonography, computed tomography and magnetic resonance imaging examinations did not detect recurrence or metastases of medullary thyroid carcinoma (MTC) in a patient with a rapidly rising serum calcitonin concentration after total thyroidectomy. Scintigraphy with technetium-99m labelled anti-carcinoembryonic antigen antibody, 99mTc-colloid and iodine-131 metaiodobenzylguanidine indicated liver metastases. The three scintigrams were to some extent discrepant but from the combined information the diagnosis of hepatic metastases could be established; it was subsequently verified by sonography and aspiration biopsy. This case demonstrates the usefulness of applying nuclear medicine imaging methods for the localization of hepatic MTC metastases.

3-Iodobenzylguanidine↗
PubMed1994

Imaging rheumatoid arthritis joints with technetium-99m labelled specific anti-CD4- and non-specific monoclonal antibodies.

A direct comparison of the joint-imaging properties of inflammation-specific- and non-specific monoclonal antibodies (Mabs) was possible in a patient suffering from long-standing, severe rheumatoid arthritis (RA). This patient received an anti-CD4- and an anticarcinoembryonic antigen (anti-CEA) Mab, both labelled with technetium-99m, 9 days apart from each other. The anti-CD4 Mab was superior to the isotype-matched anti-CEA Mab in imaging inflamed joints. In the knee joint, the target-to-background ratio of the synovial membrane (SM) activity in comparison to that of adjacent large vessels was 1.22 (SM/muscle 1.55) for the anti-CD4 Mab and 0.53 (SM/muscle 0.92) for the anti-CEA Mab, in both cases 4 h after injection of the immunoglobulin. Since the CD4 antigen is present on the surface of T-helper lymphocytes and macrophages infiltrating the inflamed synovial membrane, imaging with the anti-CD4 Mab may allow more specific detection of inflammatory infiltrates in RA.

Aged↗
PubMed1994

Current perspectives in the use of monoclonal antibodies for detection and treatment of head and neck tumors.

Squamous cell carcinomas (SCC) represent the vast majority of all malignant tumors of the head and neck. The development of distant metastases is now more often observed among these tumors than in the past. The department of Otolaryngology-Head and Neck Surgery, Free University Hospital has focussed upon the use of monoclonal antibodies (mAb) for treating SCC metastases. MAb E 48 was selected after it was shown to react strongly to SCC and minimally to normal tissues. In animal models clear tumor visualization and impressive tumor regression occurred when the antibody was linked to a suitable isotope. A diagnostic phase I/II study for the detection of lymph node metastases has entered 51 patients with head and neck cancer. Biodistribution data, acquired from surgical specimens, has shown an average tumor uptake of 30m%/g tumor tissue of the injected dose of mAb E 48. Extrapolation of data from therapeutic animal studies to these findings suggests that radioimmunotherapy can be effective in head and neck cancer patients, notably as adjuvant therapy in patients with a high chance of developing distant metastases.

Animals↗
PubMed1992

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin.

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3-5 days later by 100-150 micrograms of indium-111 streptavidin, at the specific activity of 280-370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1-8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1-30:1) and 45:1 (range 12:1-120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1-30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01-0.3) for recurrences and 0.05 for primary tumour (range 0.005-0.2). Over 24-48 h 14% i.d. (range 8-18% i.d.) was found in the urine, 14% i.d. (range 6-29% i.d.) in the blood and 63% i.d. (range 56-70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer.

Bacterial Proteins↗
PubMed1992

Alterations in an indium-111 Fab' under conditions of utilization.

This study was conducted to investigate alterations that occur in an indium/111 Fab' of a monoclonal antibody following its in vivo administration. Patients were infused with 111In-Fab' of the monoclonal antibody ZCE-025. Serum and urine specimens were collected from these patients. Starting materials, serum, urine and controls samples were studied by electrophoresis. Animal distribution studies were performed in normal Balb/c mice and, in some cases, nude mice bearing a carcinoembryonic antigen (CEA)/producing human colon tumour since the antibody targets CEA. The studies indicated that the molecule circulated almost totally intact for at least 4 h and to a considerable extent for 24 h, with some evidence for in vivo fragmentation by 24 h. Evidence was also obtained suggesting the formation of a high molecular weight species in some patients. Shortly after infusion, some of the 111In in the urine appeared as the intact Fab', but within hours the majority migrated electro-phoretically as low molecular weight species. We conclude that while the majority of the 111In-Fab' of this particular antibody remains intact and immunoreactive following its administration, the molecule is structurally changed to some degree shortly after its infusion into humans. Since each monoclonal antibody is unique, the degree and rapidity of degradation of its Fab' in vivo could vary markedly from the above and possibly adversely effect its utility as a radiopharmaceutical.

Animals↗
PubMed1992

Lymphoma imaging with a new technetium-99m labelled antibody, LL2.

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

The binding parameters of radiolabelled monoclonal F (ab')2 and Fab' fragments relative to immunoglobulin G in reactions with surface-bound antigens.

The binding parameters of iodine-125-labelled intact monoclonal immunoglobulin G (IgG), F(ab')2 and Fab' fragments were compared. The study was carried out with the two monoclonal antibodies (MoAbs) K13 and K16 specific for human Ig light chains kappa and lambda, respectively. When testing the 125I-MoAbs against monodisperse polymer particles coated with the specific antigens, the Ka for the F(ab')2 fragments were similar to that for IgG, while the Ka for the Fab' fragments were reduced to 10%-20% of that for IgG. The number N of effective target sites revealed with Fab' was higher than with F(ab')2 and IgG, presumably because less surface area is occupied by the small Fab' molecules. The immunoreactive fraction F ranged according to IgG greater than F(ab')2 greater than Fab'. The explanation of the moderate difference between the Ka of the monoclonal Fab' and the divalent IgG and F(ab')2 was that the divalent molecules were not divalently attached to the particles. When testing the same antibody preparations against human lymphoma cells producing Ig with light chains kappa or lambda, the binding results were less reliable than when particles were utilised, presumably due to antigen shedding. Different MoAbs vary in their loss of immunoreactivity due to enzymatic degradation and the radiolabelling procedure. The preparation of the radiolabelled fragments should therefore be optimized for each MoAb, and evaluation is necessary before injection. Artificial targets with a low leakage of antigen, like the monodisperse polymer particles here applied, are recommended for the in vitro evaluation of the immunoreactivity of labelled MoAb preparations.

Animals↗
PubMed1992

Tumour localization and pharmacokinetics of iodine-125 human monoclonal IgM antibody (COU-1) and its monomeric and half-monomeric fragments analysed in nude mice grafted with human tumour.

Human monoclonal IgM antibodies reactive with cancer-associated antigens may not have the optimal imaging capability due to their large size. Fragmentation of human IgM is less than straight-forward due to the loss of immunoreactivity. From the human monoclonal IgM antibody COU-1 we have prepared monomeric and half-monomeric fragments, which retain the ability to bind to colon cancer cells in vitro. The pharmacokinetics and tumour localization were evaluated in nude mice bearing human colon adenocarcinoma and human melanoma grafts. Faster clearance from the circulation was seen for the smaller half-monomeric fragment with a half-life (rapid phase/slow phase) of 2 h/16 h compared with the intact antibody, 4 h/25 h, and the monomeric fragment, 3 h/27 h. Intact COU-1 as well as the fragments accumulated in the colon tumour graft. Higher amounts of radioactivity were found in the colon tumour as compared to normal organs for intact COU-1 at days 4 and 6, for the monomeric fragment at day 4, and for the half-monomeric fragment at day 2 after injection. This investigation demonstrates the favourable biodistribution of the half monomeric COU-1 fragment. The fast clearance of this fragment resulted in a tumour-to-muscle ratio as high as 22 on day 2 after injection. Also, only this fragment gave a positive tumour-to-blood ratio. Normal IgM and its fragments were used as controls. Radioimmunoscintigraphy demonstrated the colon tumour discriminatory properties of each of the three iodine-labelled antibody preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Evaluation of monoclonal idiotypic-specific antibodies as clearing antibodies for enhancement of target localisation by tumour-specific monoclonal antibodies: diversity of effects in nude mice with human tumour xenografts.

Three tumour-specific monoclonal antibodies (MoAbs) showed localisation in human tumour xenografts in nude mice, although the tumour discrimination was limited by the survival of a greater proportion of the MoAb in the blood and body as a whole. An attempt was made to increase tumour discrimination by the subsequent administration of syngeneic idiotypic-specific MoAbs (anti-id) directed against the first antibodies, in the expectation of clearing excess of the first MoAb from the circulation. With one MoAb (NCRC-2), its anti-id (NCRC-60) did effectively clear it from the blood, and, at least within a few hours, the tumour-to-blood ratios were increased. After longer periods, however, the tumour levels of NCRC-2 were also reduced, and the tumour discrimination was no longer increased. With another MoAb (NCRC-23) the tumour levels were reduced to a greater extent than were the blood levels in mice treated with its anti-id (NCRC-59), so that rather than being increased the tumour discrimination was actually reduced to about a third of that in control mice. With a third MoAb (NCRC-48), there was no effect on the tumour or blood levels within a few hours of injection of its anti-id (NCRC-62), and so there was no short-term effect on tumour discrimination. Subsequently, however, the tumour levels were slightly reduced, while the blood levels increased in mice treated with anti-id compared with control mice, so that the tumour-to-blood ratios decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evaluation of a technique for the intraoperative detection of a radiolabelled monoclonal antibody against colorectal cancer.

Occult tumour deposits may be localised at operation with a radiation detecting probe following the administration of a radiolabelled monoclonal antibody (MoAb) recognising a tumour-associated antigen. We have recently evaluated the clinical usefulness of this technique in detecting primary colorectal tumours targetted with an indium-111 MoAb. In the present study the physical characteristics of the two detector systems used were investigated; a sodium iodide [NaI(Tl)] scintillation detector and a cadmium telluride (CdTe) semiconductor probe. Limitations of the technique in use have been examined by testing the statistical significance of tumour detection using an abdominal phantom based on the currently available clinical biodistribution data for tumour uptake of radiolabelled MoAbs. The effect of tumour volume, antibody uptake, collimation and counting conditions was examined. Results indicate that tumours of 10 ml volume may be detected with the NaI(Tl) probe at the lowest levels of radiolabelled antibody uptake currently reported in the literature but that at higher published levels, lesions as small as 1 ml may be identified with both detector systems. Detector sensitivity and limited antibody specificity restrict the usefulness of the technique, although moderate improvements in tumour uptake may allow the detection of tumour deposits not clinically apparent. The statistical significance criterion used for this study could be an accurate and reliable indicator for tumour detection in vivo.

Colorectal Neoplasms↗
PubMed1991

Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody.

Immunoscintigraphy with a technetium-99m murine monoclonal IgG1 antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE.

Adolescent↗
PubMed1992

Correlative imaging study in the diagnosis of ovarian cancer recurrences. The INSERM Research Network (Nantes, Rennes, Reims, Villejuif, Saclay), France.

A correlative imaging study was carried out in 61 female patients previously treated for ovarian carcinoma. Upon suspicion of recurrence, abdominopelvic immunoscintigraphy (IS) using F(ab')2 fragments of indium-111-labelled OC 125 monoclonal antibody was performed in all patients, Ultrasonography (US) and computed tomography (CT) were performed 53 and 37 times, respectively. The diagnostic accuracy of the different imaging techniques was studied per site (abdomen and pelvis) and per patient. The diagnostic accuracy of planar scintigraphy (PS) was slightly lower than that of emission computed tomography (ECT): 66% vs 73% for abdomen, 65% vs 72% for pelvis, and 78% vs 84% in analysis per patient. The accuracy of IS (PS and ECT combined) was markedly better than that of US and CT for abdomen (IS = 73%; US = 30%; CT = 47%), pelvis (IS = 73%; US = 37%; CT = 52%) and analysis per patient (IS = 85%; US = 43%; CT = 59%). The results of IS and morphological imaging techniques (MIT: US and/or CT) were correlatively analysed with the frequency of recurrence. When IS and MIT were both negative, the frequency of non-recurrence was 14/23 for abdomen, 7/12 for pelvis and 8/13 in analysis per patient. On the other hand, when both IS and MIT were positive, the frequency of recurrence was high (9/9 for abdomen, 17/21 for pelvis and 24/26 for analysis per patient). It was also found that a positive IS associated with a negative MIT was still highly suggestive of recurrence (17/21 for abdomen, 16/22 for pelvis and 17/19 for analysis per patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.

Animals↗