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PubMed1993

Radioimmunodetection of rat and rabbit cartilage using a monoclonal antibody specific to link proteins.

Biodistribution analysis using [125I]Fab-6F3 specific to link proteins from human articular cartilage performed in rats by autoradiography showed a high concentration of radioactivity in all cartilaginous tissues. Preliminary immunoscintigraphic assays were performed in rabbits. Front and side view images of whole animals exhibited high uptake in cartilage tissue of the knee articulation, in the invertebral disk and the humeral head. This fixation was still detected 24 h post-injection, although high washout of radioactivity was observed.

Animals↗
PubMed1995

Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice.

Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered 125I- and 111In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using 111In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL.

Adult↗
PubMed2004

Radioimmunodetection and radioimmunotherapy of head and neck cancer.

Radiolabeled monoclonal antibodies (MAbs) can add a dimension to diagnostic imaging and staging of metastatic head and neck cancer, as well as in eradication of this disease. The vast majority of malignancies arising in the oral cavity, pharynx and larynx are squamous cell carcinomas. This common cellular origin makes it attractive to search for appropriate tumor-associated antigens, which are preferentially expressed in these neoplasms. Radiolabeled MAbs directed against these antigens can be used for tumor detection and selective therapy, known as radioimmunoscintigraphy and radioimmunotherapy, respectively. The combination of MAbs with positron emission tomography (PET) is an attractive novel option to improve tumor detection and to facilitate MAb quantification in a therapeutic setting. Basic aspects of tumor targeting with MAbs, as well as a review of the clinical trials reported in the literature, including own results, are presented.

Antibodies, Monoclonal↗
PubMed1992

Radioimmunodetection of human bladder tumor xenografts in nude mice with radiolabeled monoclonal antibodies.

The tumor targeting potential of two monoclonal antibodies (mAbs) reacting with growth-regulated surface glycoproteins of human bladder cancer was investigated. The mAb T16 reacts more intensely with stationary cells while the mAb T43 is preferentially reactive with exponentially growing cells. The test target was T24 human bladder cancer cells grown subcutaneously in 30 nude mice. Controls for tumor specificity were human lung cancer cells grown on the contralateral side. Purified mAb's T16 and T43, and Om5, a non-reactive control, were radiolabeled with 131-Iodine and injected intravenously in doses ranging from 50 to 300 microCi in tumor-bearing animals. Consistent images of the bladder cancer xenografts were obtained at 48 and 72 hours with tumors as small as 0.1 gm. High resolution tumor images were obtained only with the reactive antibodies and according to their in vitro specificity. These results demonstrate that the two mAbs T16 and T43 can specifically and sensitively localize human bladder cancer cells in vivo.

Animals↗
PubMed1994

Peroperative radioimmunodetection of ovarian carcinoma using a hand-held gamma detection probe.

Radioimmunoscintigraphy (RIS) can be used in the preoperative localisation of ovarian carcinoma to demonstrate uptake of radiolabelled monoclonal antibodies into neoplastic tissue. The tissue uptake of radiotracer was evaluated at laparotomy in 16 patients with suspected ovarian cancer who had preoperative RIS using technetium-99m-labelled monoclonal antibodies SM3 and H17E2. A gamma detection probe (gamma DP) was used to measure uptake in possible tumour deposits at operation and also the uptake in tissues resected for histology. The percentage uptake of the initial injected dose of radiotracer was also measured in resected tissues. Activity was found to be significantly higher in malignant than in non-neoplastic tissue by all three methods of evaluation. The gamma DP used peroperatively yielded a 82% sensitivity with a 72% specificity for an uptake ratio of 1.5:1. When tissue was examined immediately after resection, for a 100% specificity the sensitivity was 64%. In vitro measurements of monoclonal antibody uptake by tissue similarly gave a 65% sensitivity with a 100% specificity. Peroperative and immediate post-operative measurements of tissue radioactivity can be performed quickly and conveniently, and in some cases may be of benefit in the localisation of tumour at laparotomy and in providing extra information when tissue is examined by frozen section.

Adult↗
PubMed2005

Radioimmunodetection and therapy of breast cancer.

Breast cancer is the second most-common cause of cancer death in women in the United States. Although more than 60% of patients can now be cured by initial treatment, the rest, although perhaps receiving palliation with currently available therapy, will die of their disease. Early detection of micrometastasis and improved treatment strategies are needed. Monoclonal antibody (mAb)-based imaging and tumor targeted therapy holds the potential to impact these problems. The most significant results of systemically administered antibody-based radiopharmaceuticals for detection and targeted therapy (radioimmunotherapy [RIT]) of breast cancer give strong evidence that this potential can be realized. Interest in immunoimaging recently has focused on small mAb modules used with 18F, 64Cu, or 124I to detect minimal disease in breast cancer by positron emission tomography or single-photon emission computed tomography. Reported therapy trials in advanced breast cancer have yielded objective responses and minimal toxicity. These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting. RIT evaluated in clinical breast cancer trials has delivered as much as 4000 cGy to metastatic breast cancer per therapy dose with marrow stem cell support. Preclinical studies have demonstrated further promising strategies for breast cancer. RIT studies must address the key issue: enhancing the therapeutic index (tumor effect verses most sensitive normal tissue (bone marrow) effect). Approaches now include newly engineered mAb, scFv modular constructs, blood clearance on demand, enhanced pretargeting, applications of both alpha and beta emitting radionuclides, and combination therapy using molecular triggers for therapeutic synergy. These strategies for detection and treatment of metastatic breast cancer should lead to notable clinical impact on management and cure of breast cancer.

Antibodies, Monoclonal↗
PubMed1997

Radioimmunodetection of neuroblastoma cells with I-131-radiolabelled antibodies.

The murine anti-neuroblastoma monoclonal antibodies 15/7 and 19/1/4 should be tested for specific radiolocalization of neuroblastoma by immunoscintigraphic imaging of this tumour growing in mice. Radioiodination of both antibodies was done by chloramine-T method resulted in an immunoreactivity of 75%. The calculated specific activity varied from 51.1 to 126.2 kBq/microgram IgG. In each case, about 500 kBq of labeled antibodies were intraperitoneally injected into human neuroblastoma (SK-N-MC, SK-PN-DW and IMR 5) xenografted severe complete immunodeficient (SCID) mice. Whole-body scintigraphy was performed daily by a scintiscanner to localize the tumour site. After last scanning principal organs were removed and their I-131-uptake was determined by measuring the impulse rate. The best scintigrams were done with I-131-19/1/4 at the second day after antibody injection. Radioconjugates were accumulated at highest in the tumour at the third day after application of 15/7 and 19/1/4 with a tumour uptake of 0.4 and 2.2 per cent of injected dose per gram (%ID/g), respectively. The 15/7-moAbs was accumulated approximately 9-fold higher in the SK-N-MC and SK-PN-DW grafts than in principal organs, whereas the tumour/non-tumour-ratio of the 19/1/4 moAb was 3:1. The results indicate the efficacy of these two neuroblastoma antibodies in radiolabelling and their usefulness for tumour imaging of neuroblastoma engrafted SCID-mice.

Animals↗
PubMed1994

Radioimmunodetection of colorectal carcinoma with 111In-labelled monoclonal antibody IVP ZCE 025 (a tissue culture-produced anti-CEA MAb).

The aims of this prospective, nonrandomized phase I/II study were to evaluate (1) the safety and (2) the detection rate of tissue culture-derived, 111In-labelled anti-CEA monoclonal antibody IVP ZCE 025 in patients with primary, metastatic and occult colorectal carcinomas. 111In-IVP ZCE 025 imaging correctly identified 31 of 37 primary colorectal carcinomas, 10 of 19 hot liver metastases, 11 of 16 distant metastases and seven of seven local tumour recurrences. Previously unsuspected tumours were detected by IVP ZCE 025 imaging in 11 of 34 patients. The scans were also true negative in four patients. The overall performance characteristics of IVP ZCE 025 at monoclonal antibody doses of 1.0-5.0 mg were comparable to those obtained with 40.0 mg ascites-produced ZCE 025. No clinical or biochemical adverse reactions were encountered in the 61 patients entered into this study.

Adult↗
PubMed2005

Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy.

This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.

Antibodies, Neoplasm↗
PubMed1993

Radioimmunodetection of ovarian cancer.

Radioimmunoscintigraphy (RIS) is a potentially valuable method for the detection of primary, secondary and recurrent malignant tumours. Antigens that have been used for monitoring as well as for RIS of ovarian carcinomas include CA 125, PLAP, HMFG, and CA 19-9. Between 70 and 100% of the tumours have been detected at RIS when these antigens have been used. Conventional methods, e.g., computerized tomography (CT) and ultrasonography (US), demonstrate similar or lower detection rate than RIS for tumour diagnosis. RIS gives additional information to conventional radiological methods (CT and US) for the detection of occult ovarian carcinomas. A review of earlier investigations is given and our own recent results using PLAP as a target antigen are presented. The future potential of the technology is discussed.

Adult↗
PubMed1993

Radioimmunodetection of head and neck cancer. A review.

Radiolabeled antibodies can add a dimension in the diagnostic imaging and staging of metastatic head and neck malignancies. In the oral cavity, oropharynx and larynx the vast majority of malignancies are squamous cell carcinomas. This common cellular origin makes it feasible to search these neoplasms for appropriate tumor-associated antigens which can be used for radioimmunoscintigraphy. The pretherapeutic staging of head and neck malignancies, including salivary gland tumors, is based on clinical findings and conventional radiology (computerized tomography, magnetic resonance imaging, ultrasonography). The routine use of monoclonal antibodies for imaging head and neck malignancies was made possible by the production of several monoclonal antibodies to tumor-associated membrane antigens. A review of the clinical trials reported in the literature, and our own results with 111In-labeled anti-carcinoembryonic antigen (CEA) antibody in 42 patients are presented.

Animals↗
PubMed1993

Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics.

We performed radioimmunoscintigraphy (RIS) and/or pharmacokinetic (PCK) studies in 12 patients with primary or metastatic colorectal carcinoma, utilizing an intravenous administration of 1-4 mCi (1 mg) of 131I-B72.3 monoclonal antibody. Metastatic lesions were correctly identified in 4/8 patients by RIS. Two patients with small lesions (> 2 cm diameter) had a false-negative RIS scan. Two patients had a true-negative RIS scan. Optimal images were obtained at 1 week postinjection. PCK studies showed that the plasma clearance of 131I-B72.3 was biexponential with an alpha-phase half-life ranging from 0.5 to 7.1 hr and a beta-phase half-life ranging from 47.5 to 85.3 hr. Systemic and renal clearance data indicated that 131I-B72.3 was cleared very slowly and almost entirely by deiodination. This pilot study was conducted to gain an understanding of the pharmacokinetics of this radiolabeled antibody. On the basis of these data, we are now studying second-generation antibodies as part of our long-range objectives to incorporate them in early detection and treatment protocols.

Adult↗
PubMed1999

Retargeting interleukin 13 for radioimmunodetection and radioimmunotherapy of human high-grade gliomas.

A vast majority of patients with glioblastoma multiforme (GBM), a high-grade glioma, overexpress abundant amounts of a receptor for interleukin (IL)-13 in situ. This receptor is more restrictive because it is IL-4-independent and therefore differs from the IL-13/4 signaling receptor of normal tissue that is shared with IL-4. We previously identified one of the sites on the human IL (hIL)-13 molecule that is important for its interaction with the IL-13/4 receptor, a residue of glutamic acid at position 13. In this study, we mutated the cytokine and produced hIL-13.E13Y, in which the glutamic acid was substituted by tyrosine. This additional tyrosine residue was therefore strategically located within the region of IL-13 interaction with the signaling physiological receptor. hIL-13.E13Y did not transduce signals through the IL-13/4 receptor, whereas its interaction with the more restrictive, GBM-associated receptor remained intact. The mutated hIL-13 could be readily radiolabeled. Radiolabeled hIL-13.E13Y produced specific autoradiographic images of human GBM specimens. We demonstrate an effective way to redirect hIL-13 to its more restrictive receptor found in high-grade gliomas by mutagenizing the cytokine, and, concomitantly, we equipped hIL-13 with an additional tyrosine residue for higher specific activity radiolabeling.

Amino Acid Sequence↗
PubMedDate not supplied

Radioimmunodetection of colorectal carcinoma.

BACKGROUND/AIMS: The aim of the study is detection of the recurrences and metastases of colorectal carcinomas using 111In-labeled antibodies B72.3. METHODOLOGY: Fourteen patients underwent planar immunoscintigraphy and/or tomoscintigraphy. RESULTS: With tomography in comparison to planar scintigraphy, we can access better distinction of tumor and estimation of its size. Other imaging methods (computed tomography, ultrasonography) have an advantage in detection of liver metastases, while immunoscintigraphy is more specific for the assessment of malignant abdominal tumors and extrahepatic metastases. CONCLUSIONS: The first results point out that Oncoscint CR-103 can be useful in diagnosis of recurrences and metastases of colorectal carcinoma, viability assessment after radiotherapy and in the choice of the adequate surgical treatment in dependence of the spread of the disease.

Adenocarcinoma↗
PubMed1992

Radioimmunodetection of occult carcinoembryonic antigen-producing cancer.

This study evaluates the ability of 111In-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody (Mab) ZCE-025 to detect sites of occult cancer in patients with elevated serum CEA who have negative or equivocal CT scans. One hundred forty patients suspected of having occult cancer were evaluated. Except for elevated CEA levels, all had negative work-ups, including negative or inconclusive CT scans. Eighty-two patients (59%) had positive scans and 58 (41%) had negative scans. Seventy-five of the 82 patients with positive scans had confirmation of at least one Mab-positive lesion (91% positive predictive value). Thirty-eight of the 58 patients with negative scans had negative follow-up (66% negative predictive value). The Mab scan correctly identified at least one site of tumor in 75 of the 95 patients with recurrent or metastatic disease (79% sensitivity) and correctly predicted the absence of disease in 38 of 45 patients (84% specificity).

Aged↗