Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Radioimmunodetection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1989

Radioimmunoscintigraphy of prostate cancer.

The development of hybridoma technology has increased research efforts and clinical applications in the area of radioimmunodetection. Despite the many investigative antibodies directed against prostatic tissue or prostate cancer cell lines, only two have been tested in clinical trials. A 111In-labeled antibody directed against prostate-specific antigen, the best available serum tumor marker for prostate cancer, has shown poor sensitivity in limited clinical radioimmunoimaging trials. Monoclonal antibodies against prostatic acid phosphatase have shown better imaging results, particularly at higher antibody doses (greater than or equal to 40 mg). The limitations of this antibody include the poor results in detecting soft tissue lesions, including the primary lesion; the development of human antimouse antibodies in 50% of the patients at doses greater than or equal to 40 mg; the expense of the antibody; and the fact that better results are currently attainable by other less expensive imaging modalities. If and when a more suitable antibody or fragment is developed, the prospect of improved staging and new treatments using immunologic conjugates carrying therapeutic agents may become realities. Until such time, prostatic cancer will be staged with other currently available imaging modalities and conventional therapies with their limitations will remain state of the art.

Acid Phosphatase↗
PubMed1989

Future role of radiolabeled monoclonal antibodies in oncological diagnosis and therapy.

This review discusses the current limitations and future prospects of radiolabeled antibodies in cancer imaging (radioimmunodetection, or RAID) and therapy (radioimmunotherapy, or RAIT). Aspects such as the antibody vehicle, antigen target, radiolabel, tumor, host, and RAID and RAIT procedures are considered. In the short timespan for the development of RAID, tumors as small as 0.5 cm, which are sometimes missed by other radiological methods, can now be imaged with antibody fragments labeled with suitable radionuclides (eg, 111In, 123I, and 99mTc), particularly when single photon emmission computed tomography (SPECT) scanning methods are employed. 99mTc is clearly the preferred label, and the recent development of simple and rapid methods to attach this isotope to antibodies should be a welcome advance for the more widespread use of RAID. In RAIT, radiosensitive neoplasms, such as lymphomas, are already showing impressive responses to 131I-labeled antilymphoma murine monoclonal antibodies. Therefore, the successful conjugation of beta- and alpha-emitters to "humanized" monoclonal antibodies should provide a new generation of promising cancer therapeutics.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Radioimmunolocalization of head and neck tumors with a new monoclonal antibody against the EGF receptor. Preliminary results].

OBJECTIVE: To show the results of Radioimmunodetection (RID) using Cuban monoclonal antibody (MoA) anti-egf-ior-egf-r3 labeled with 99mTc for the detection of primary tumors and/or metastases of head and neck epithelial malignant tumors. MATERIAL AND METHODS: Thirteen patients aged from 16-62 years (mean: 54.8 years) with primary tumors and metastases in the regional cervical lymph nodes were retrospectively evaluated. The labelling dose was 1480-2220 MBq (40-60 mCi). Planar images were performed after 10 minutes and together with SPECT images after 18-24 hours following MoA administration. The matrix was 128 x 128. SPECT images were reconstructed using the Butterworth 4/16 filter. A positive result was defined when the lesions were visualized. RESULTS: RID localized 11 of the known primary tumors in the 13 patients studied. In the two other patients, in whom the primary tumor site was unknown, cervical lymph node metastases were found. The results of 3 of the RID were false negative but in the other 10, RID was able to localize the primary tumor and cervical lymph node metastases. Sensitivity was 77 % and the predictive positive value was 100 %. CONCLUSIONS: The results of this study show that the Cuban MoA ior-egf-r3 can be employed for RID of primary head and neck tumors and their metastases. The radiation dose is adequate for RID.

Adolescent↗
PubMedDate not supplied

Experimental pretargeting studies of cancer with a humanized anti-CEA x murine anti-[In-DTPA] bispecific antibody construct and a (99m)Tc-/(188)Re-labeled peptide.

The aim of this study was to localize (99m)Tc and (188)Re radionuclides to tumors, using a bispecific antibody (bsMAb) in a two-step approach where the radionuclides are attached to novel peptides incorporating moieties recognized by one arm of the bsMAb. A chemically cross-linked human/murine bsMAb, hMN-14 x 734 (Fab' x Fab'), anti-carcinoembryonic antigen [CEA] x anti-indium-DTPA was prepared as a prelude to constructing a fully humanized bsMAb for future clinical application. N,N'-o-Phenylenedimaleimide was used to cross-link the Fab' fragments of the two antibodies at their hinge regions. This construct was shown to be >92% pure and fully reactive with CEA and a divalent (indium)DTPA-peptide. For pretargeting purposes, a peptide, IMP-192 [Ac-Lys(In-DTPA)-Tyr-Lys(In-DTPA)-Lys(TscG-Cys-)-NH(2) ¿TscG = 3-thiosemicarbazonylglyoxyl¿], with two indium-DTPAs and a chelate for selectively binding (99m)Tc or (188)Re, was synthesized. IMP-192 was formulated in a "single dose" kit and later radiolabeled with (99m)Tc (94-99%) at up to 1836 Ci/mmol and with (188)Re (97%) at 459-945 Ci/mmol of peptide. [(99m)Tc]IMP-192 was shown to be stable by extensive in vitro and in vivo testing and had no specific uptake in the tumor with minimal renal uptake. The biodistribution of the hMN-14 x murine 734 bsMAb was compared alone and in a pretargeting setting to a fully murine anti-CEA (F6) x 734 bsMAb that was reported previously [Gautherot, E., Bouhou, J., LeDoussal, J.-M., Manetti, C., Martin, M., Rouvier, E., and Barbet, J. (1997) Therapy for colon carcinoma xenografts with bispecific antibody-targeted, iodine-131-labeled bivalent hapten. Cancer 80 (Suppl.), 2618-2623]. Both bsMAbs maintained their integrity and dual binding specificity in vivo, but the hMN-14 x m734 was cleared more rapidly from the blood. This coincided with an increased uptake of the hMN-14 x m734 bsMAb in the liver and spleen, suggesting an active reticuloendothelial cell recognition mechanism of this mixed species construct in naive mice. Animals bearing GW-39 human colonic cancer xenografts were injected with bsMAb (15 microg) and after allowing 24 or 72 h for the bsMAb constructs to clear from the blood (hMN-14 and murine F6 x 734, respectively), [(188)Re]IMP-192 (7 microCi) or [(99m)Tc]IMP-192 (10 microCi) was injected at a bsMAb:peptide ratio of 10:1. Tumor uptake of [(99m)Tc] or [(188)Re]IMP-192 was 12.6 +/- 5.2 and 16.9 +/- 5.5% ID/g at 3 h postinjection, respectively. Tumor/nontumor ratios were between 5.6 and 23 to 1 for every major organ, indicating that early imaging with (99m)Tc will be possible. Radiation absorbed doses showed a 4.8-, 7.2-, and a 12.6 to 1.0 tumor to blood, kidney, and liver ratios when (188)Re was used. Although this new bsMAb pretargeting approach requires further optimization, it already shows very promising targeting results for both radioimmunodetection and radioimmunotherapy of colorectal cancer.

Animals↗
PubMed1982

Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies.

Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123I and 125I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at various times from immediately to 65 days after injection. Visual displays of the images were processed by standard computer techniques. The model used a human colon-cancer cell line, HT29, and the monoclonal antibody, AUA1, which is specific to an epithelial proliferating antigen. Tumour detection was achieved in all the mice. The smallest tumour detectable appeared to be about 1 mm in diameter. The degree of antibody uptake in a tumour depended on its size and the blood supply of its surrounding tissues We believe that the technology and skills are now available for accurate radioimmunodetection of cancer in man.

Animals↗
PubMed1987

Selective localisation of two radiolabelled anti-sarcoma monoclonal antibodies in human osteosarcoma xenografts.

Two mouse monoclonal antibodies (MoAbs), TP-1 and TP-3, previously shown in immunohistochemical studies to react with osteosarcomas, were labelled with 125I or 131I and evaluated for their ability to localise to human osteogenic sarcoma xenografts after intravenous injection. The radiolabelled TP-1 and TP-3 MoAbs had immunoreactive fractions of 70% and 67%, respectively, and bound to target cells with binding constants of 8.5 X 10(8) M-1 and 4.0 X 10(9) M-1, respectively. After injection of labelled TP-3 IgG, approximately 16% of the dose X g-1 tissue was found in the tumour after 24 hours. Maximum tumour/blood radioactivity ratios of 6-7 were achieved 3-4 days after antibody injection, while the ratios for the normal tissues were less than 1. The tumours could be clearly visualised by whole-body gamma scintigraphy without the need for subtraction techniques. The TP-1 IgG accumulated to a large extent also in the spleen. Hence, with this antibody the tumour was less well delineated from the adjacent normal tissues. However, the F(ab')2 fragments, derived from the TP-1 IgG, gave tumour/blood ratios up to approximately 40 after 3-4 days and yielded sharp gamma scintigrams of the tumour. Specificity of the antibody localisation was indicated by the lack of accumulation in a contralateral melanoma xenograft and the failure of 2 isotype-matched irrelevant MoAbs to localise to the sarcomas. With the F(ab')2 fragments satisfactory images could be obtained already after 16 hours. The results suggest that this preparation may be useful in clinical radioimmunodetection of osteogenic sarcomas.

Animals↗
PubMed1988

Characterization of the binding epitope of a monoclonal antibody to sulphatide.

An IgG1 monoclonal antibody, Sulph I, reacting with sulphatide (3'-sulphogalactosylceramide), was produced by immunizing Balb/c mice with that glycolipid coated on Salmonella minnesota bacterial membrane. Radioimmunodetection of the binding of the monoclonal antibody to structurally related glycolipids adsorbed to microtitre plates or chromatographed on thin-layer plates was used to determine its binding epitope. The antibody showed similar binding avidity to three sulphated glycolipids: sulphatide, sulpholactosylceramide and seminolipid. Lysosulphatide did bind the antibody, but, compared with sulphatide, 30 times more antigen was needed for half-maximal binding. Bis(sulphogangliotriosyl)ceramide and bis-sulphogangliotetraosylceramide did not bind the antibody. These results suggest that terminal galactose-3-O-sulphate and part of the hydrophobic region of the glycolipid are recognized by the Sulph I antibody.

Antibodies, Monoclonal↗
PubMed1990

[A trial with immunotherapy of ovarian cancer by idiotype vaccination. Activation of the idiotype network in patients with advanced ovarian cancers by treatment with monoclonal antibody OC125].

Up to date, the positive effect of immunotherapy, using tumour-associated antigens or tumour cells of ovarian carcinomas, is still vague. Another and effective approach to overcome an experimentally induced tolerance, is the presentation of an definitive antigen in a different surrounding by the induction of the idiotypic network. Antibodies against a tumour-associated antigen are used to induce following antibodies, which are directed against the variable antigen-binding group, the so-called idiotype of the antibody-vaccine. Then, the induced antibodies carry a mirror image of the tumour-associated antigen and are therefore able to modulate the host's immune response against the tumour. For the induction of this system, we used the monoclonal antibody OC125 as a F(ab)2-fragment, which is directed against the tumour-associated antigen CA125 of epithelial ovarian carcinomas. 12 patients with advanced ovarian carcinomas received antibody fragments of the OC125 in the course of radioimmunodetections since 1985. Until April 1990 only these 5 patients, who developed the anti-idiotypic antibodies after the vaccination, are still alive. Our first results with the induction of the idiotypic network system for patients with advanced ovarian carcinomas indicate, that in spite of the same surgical and chemotherapeutical treatment, patients show a delayed clinical course after the induction of the idiotypic system. The transfer of the definitive tumour-associated antigen in an idiotypic antigen, seems to modulate the immunoresponse of the patients and in this way also the clinical course of a malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1990

Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2.

Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. We engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors. To this end, the constant region of the human gamma 1 chain was mutated by deleting the second domain (CH2). Here we show that the CH2-deleted antibody (ch14.18-delta CH2) was cleared from the blood of athymic (nu/nu) mice bearing human melanoma tumors with the same kinetics as human IgG F(ab')2. At a beta t1/2 of 12 hr, 0.9% of the injected dose of 125I-labeled ch14.18-delta CH2 was found per milliliter of blood 24 hr after i.v. injection. In biodistribution experiments, 125I-labeled ch14.18-delta CH2 targeted specifically to melanoma xenografts, achieving optimal tumor-to-tissue ratios 12-16 hr after i.v. injection. ch14.18-delta CH2 was localized to the melanoma tumors more rapidly and with better localization ratios than the intact chimeric antibody ch14.18. Sixteen hours after i.v. injection, the tumor-to-blood and tumor-to-liver ratios of ch14.18-delta CH2 were 5 and 12, respectively, while optimal localization ratios obtained for ch14.18 were 1 and 5, respectively, but 96 hr after injection. A reagent such as ch14.18-delta CH2 should be useful for radioimmunodetection of human tumors because of reduced immunogenicity, increased targeting specificity, and rapid clearance from circulation.

Animals↗
PubMed2001

Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments.

Antibodies have long been considered to be potential anticancer agents because of their specificity for cell-membrane antigens. Applications of hybridoma and recombinant DNA technology have led to the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies for clinical use. Whole antibodies may produce anticancer effects in conjunction with the immune system by interaction with complement proteins and/or effector cells via the Fc portion of the antibody molecule. Antibodies may also neutralize circulating ligands or block cell membrane receptors and thus interrupt ligand/receptor interactions and signal transduction that are associated with proliferative or anti-apoptotic effects. The anti-idiotype network cascade provides a rationale for antibodies as vaccine therapy. Antibodies may also serve as the guiding or targeting system for other cytotoxic pharmaceutical products such as (i) radiolabeled antibodies for radioimmunodetection and radioimmunotherapy; (ii) immunotoxins; (iii) chemotherapy/antibody conjugates; (iv) cytokine/antibody conjugates; and (v) immune cell/antibody conjugates. After years of anticipation, as of late 1999 there were four monoclonal antibodies that had been approved by the U.S. Food and Drug Administration based on activity against human malignancy, all of which are in widespread clinical use. Several other products are in various stages of clinical trial testing. Monoclonal antibodies have joined interferon-alpha, interleukin-2 (IL-2), and various hematopoietic growth factors as well-established components of biological therapy, the fourth modality of cancer treatment.

Antibodies, Monoclonal↗
PubMed2001

Improved production by domain inversion of single-chain Fv antibody fragment against high molecular weight proteoglycan for the radioimmunotargeting of melanoma.

Melanoma is among the few cancers with rising incidence. Currently there is no effective treatment for metastatic disease, but improved detection of melanoma has the potential to benefit the management of patients with early disease. Radioimmunodection by imaging with single-chain Fv (scFv) antibody fragments is one such emerging diagnostic method. However, the amount of scFv that can be produced at a scale suitable for use in patients is limiting. We have previously shown that the bacterial expression of a scFv derived from a monoclonal antibody (MAb) specific for melanoma-associated proteoglycan can be increased by light chain shuffling. In this report we show that a further increase in expression yield can be obtained by reversing the usual V(H)-V(L) orientation of scFvs to V(L)-V(H). Such seemingly minor changes have previously been reported to have unexpected effects on the in vitro and in vivo binding properties of recombinant antibodies. Our results show that reversal of the V domain orientation of the scFv improves expression by 150% without an adverse effect on melanoma binding in vitro and tumor targeting in vivo. Therefore, our results show that alteration of V domain orientation can improve the production yield of clinically useful antibody fragments. When used in combination with other antibody engineering approaches for increased antibody production changing the domain orientation is a simple strategy to achieve significant improvements in the production of scFvs for tumor radioimmunodetection for patient studies.

Antibodies, Neoplasm↗
PubMed1984

Selection of monoclonal antibody to hCG which localizes in human choriocarcinoma growing in the Syrian hamster cheek pouch.

Six different monoclonal antibodies (MAbs) to human chorionic gonadotropin (hCG) were evaluated for radioimmunodetection in Golden Syrian Hamsters bearing a human choriocarcinoma in the cheek pouch (188-516 mIU of hCG/g). The affinity of three antibodies when determined were high and five of the antibodies were of IgG1 subclass. After i.v. injection of Staphylococcus Protein A (SPA) affinity purified radioiodinated antibodies, tissue distribution studies demonstrated that antibody 061 had higher target-to-nontarget ratios than the other five antibodies. The mean tumor:muscle ratio of 131I-MAb 061 was 27.5 in four animals, where the mean tumor:muscle ratio of four animals injected with 131I-labeled control monoclonal IgG1 Kappa from MOPC-21 murine myeloma (MOPC-21) was only 2.2. Sharp images of the cheek pouch tumor were obtained at five days following a tracer dose of 131I-061 MAb, but not with the same dose of a 131I-MOPC-21.

Animals↗
PubMed1988

A murine monoclonal antibody raised against human non-small cell carcinoma of the lung.

Murine monoclonal antibodies (MAbs) reactive with human non-small cell carcinoma of the lung (NSCCL) were produced following immunization with a membrane preparation of Calu-3, a human adenocarcinoma of the lung cell line grown in nude mice. Positive hybrids unreactive with normal liver membranes and human peripheral white blood cells were selected for further testing. One MAb (RS5-4H6) recognized an antigen expressed in a variety of lung and other carcinoma cell lines as detected by flow cytometry. Immunohistology showed a selectivity for normal and neoplastic lung epithelium, as well as other cancers. The antigen was detected by immunohistology in 87% of tumor specimens derived from the lung, breast, colon, kidney, and ovary. Most other normal human tissues were not stained but occasional cells of the stomach, salivary and other glands, as well as kidney tubules were reactive. This MAb is an IgG1. Western blot analysis indicated that the antibody reacts selectively with an antigen greater than 300 kD. The antigen is resistant to neuraminidase treatment and periodate oxidation, but sensitive to pronase treatment, suggesting that the epitope is peptide in nature. This antibody may be potentially useful as a targeting agent for radioimmunodetection and immunoconjugate therapy.

Adenocarcinoma↗
PubMed1991

A new murine monoclonal antibody against human hepatoma.

A murine monoclonal antibody (MAb 336) reactive with human hepatocellular carcinoma has been raised after immunizing BALB/c mice with whole HepG2 cells. MAb 336 (IgG1) was reactive with HepG2 (whole cells and membrane fractions), but not normal liver or peripheral blood cells. Immunohistological studies indicated that 12/16 hepatocellular carcinoma and 6/11 cirrhotic livers expressed MAb 336-associated antigen, and most normal human tissues and tissues derived from other cancers were unstained. Direct and competitive binding assays ruled out the possibility that this MAb reacts with alpha-fetoprotein, carcinoembryonic antigen, or ferritin. Western blot analysis indicated that MAb 336 reacts with an antigen of approximately 30,000 daltons. This MAb may be potentially useful for studying antigenic expression in hepatocellular carcinoma and as a targeting agent for radioimmunodetection and immunoconjugate therapy.

Animals↗
PubMed1987

Tumor-associated antigen expression of primary and metastatic colon carcinomas detected by monoclonal antibody 17-1A.

Murine monoclonal antibody (MAb) 17-1A has been used in radioimmunodetection and immunotherapy trials of intestinal adenocarcinoma in humans. Tumor heterogeneity of antigen expression has been recognized as a potential limiting factor in such studies. The authors report a study designed to evaluate the degree of heterogeneity of 17-1A antigen expression among primary and metastatic human colon carcinomas. All 141 specimens, including 74 primary or metastatic colonic adenocarcinomas, were evaluated with the use of an avidin-biotin complex immunoperoxidase technic on briefly fixed frozen tissue sections. All of these showed at least focal staining with MAb 17-1A. However, well- or moderately differentiated tumors generally showed diffuse cytoplasmic immunostaining, whereas poorly differentiated tumors showed minimal immunostaining with no detectable antigen in most areas. In 16 cases that had both primary and metastatic adenocarcinomas or multiple metastatic tumors, 17-1A antigen expression was similar among the tumor sites except for one case. This case showed variation in tumor differentiation and corresponding variation in 17-1A antigen expression. Of 36 additional malignant tumors that were not of colonic epithelial origin, adenocarcinomas of the stomach, duodenum, endometrium, ovary, and breast showed 17-1A antigen expression.

Adenocarcinoma↗
PubMed1988

A tumor-associated antigen in carcinoma of the pancreas defined by monoclonal antibody B72.3.

A retrospective analysis of 25 primary adenocarcinomas of the pancreas, 16 metastatic pancreatic tumors, 8 cases of chronic pancreatitis, and 3 adult normal pancreas was performed to ascertain the reactivity of monoclonal antibody (MAb) B72.3 to malignant and nonneoplastic pancreatic lesions. Formalin-fixed, paraffin-embedded sections of pancreas were evaluated by immunohistochemical techniques (avidin-biotin-peroxidase complex [ABC] method). Twenty-one of 25 malignant primary tumors were reactive, and all 16 metastatic sites expressed the B72.3 antigen. In contrast, all cases of pancreatitis and normal pancreas were either weakly reactive or nonreactive. Ten malignant and two benign pancreatic fine-needle aspirates provided results similar to those seen with fixed tissues. Because MAb B72.3 has selective reactivity for primary and metastatic pancreatic cancer, it may be of value as a diagnostic adjunct in cytologic examination or for radioimmunodetection of regional and/or distant metastases of adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1993

New imaging techniques in gastrointestinal cancer.

Impressive advances in both anatomic and functional imaging of gastrointestinal tumors have been made in recent years, with several interesting studies appearing this past year. Increasingly, different imaging modalities have been used in combination and have shown complementation and improved accuracy. Improvements in detecting and defining local versus extended sites of cancer in various gastrointestinal organs have been made by conventional methods and by newer functional tests, including positron-emission tomography, receptor scintigraphy, and radioimmunodetection. With the US Food and Drug Administration approval of the first antibody-based cancer imaging agent, a new class of biologic imaging agents is coming of age in oncology and will likely experience the most use in management of colorectal cancer, permitting improved staging and disclosure of occult disease. In addition to gamma camera imaging, these radioactive biologic targeting agents hold promise for positron-emission tomography scanning and for cancer radioimmunotherapy.

Diagnostic Imaging↗
PubMed1990

Analysis of binding of a technetium-99m-labeled monoclonal antibody to lentivirus-infected cells.

Caprine arthritis-encephalitis (CAE) is a model for the study of lentiviral infections. The authors' hypothesis is that radioimmunodetection has the potential to detect lentiviral proteins at the surface of infected cells. A monoclonal antibody (CAEV92A1) specific for a CAE virus (CAEV)-associated glycoprotein and a control antibody were radiolabeled with technetium-99m (99mTc) using the pretinning method. Cell binding assays were used to evaluate immunoreactivity and binding properties of 99mTc-labeled antibodies to CAEV-infected cells. 99mTc-CAEV92A1 bound preferentially to paraformaldehyde-fixed and live CAEV-infected cells. 99mTc-CAEV92A1 did not appear to be shed rapidly from its binding site.

Animals↗