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A Hertel

Publications and source records attributed to A Hertel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Activating anti-idiotypic human anti-mouse antibodies for immunotherapy of ovarian carcinoma.

Human anti-mouse antibodies (HAMA) are observed frequently after immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA-125. As the authors have shown previously, HAMA can cause false-positive CA-125 values in routine CA-125 immunoradiometric assay (IRMA) tumor-marker assays (in one case, up to 900 days after immunoscintigraphy). In 32 patients, the authors found a HAMA frequency of 34% (11/32: 3/7 after the first administration, 6/13 after the second, and 2/2 after the third). Ten patients developed extremely high CA-125 levels after undergoing the CIS IRMA assay (up to 80,000 U/ml) in parallel to a significant HAMA increase. The use of different assays, or HAMA removal before in vitro testing, can solve this problem. After a new CA-125 assay containing antibodies that recognize different epitopes on the CA-125 antigen (Biomira Tru-Quant OV) was applied, only mildly increased assay results or normal levels were measured. Most of HAMA-positive patients demonstrated a predominantly anti-idiotypic response, determined with two different HAMA assays. Seven patients with anti-idiotypic HAMA responses after OC-125 immunoscintigraphy remained free of tumor or had stable disease (2-42 or more months), contrary to their poor prognoses that had been made based on the underlying stages of their tumors. All of these patients are currently doing well (Karnofsky Index > 70%) and show no significant tumor progression. In light of their extremely poor prognoses (5-year survival rates of 3-5% in recurrent International Federation of Gynecology and Obstetrics III/IV stages), without further chemotherapy, these courses are extremely unusual. Preliminary in vitro experiments lead to the postulation that anti-idiotypic HAMA may trigger an antitumor effect either by suppressing the growth of CA-125-expressing cancer cells directly, or by activating the patient's immune response via induction of Ab3. Similar results are observed after immunoscintigraphy with a technetium-99m-labeled anti-CA-125 monoclonal antibody (B43.13), which the authors now also use for immunotherapy of ovarian cancer patients by repeated injections, hoping that induction of anti-idiotypic HAMA will be beneficial for prolonged survival of patients with ovarian carcinoma.

Animals↗
PubMed1994

Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody fragment in the radioimmunodetection of B-cell lymphomas.

BACKGROUND: Various monoclonal antibodies (MoAb) labeled with Iodine-131 or Indium-111 (In-111) have been investigated for radioimmunodetection of Hodgkin's and non-Hodgkin's lymphomas. Successful radioimmunotherapy also has been reported. The purpose of this pilot study was to stage non-Hodgkin's B-cell lymphomas (NHL) using whole body scintigraphy with technetium-99m (Tc-99m)-labeled murine monoclonal antibody LL2 (EPB-2) Fab' (Immunomedics, Morris Plains, NJ). Others have shown this MoAb to have specific binding to B-cell lymphomas by flow cytometry and immunofluorescence. Initial clinical studies by others have demonstrated targeting of NHL with the Tc-99m-labeled LL2-Fab'. METHODS: One milligram of the antibody was injected intravenously after being radiolabeled with 30 mCi Tc-99m. Fifteen patients with high (n = 6), low (n = 2), and intermediate (n = 7) grade NHL were studied. No adverse effects were noted. Planar whole body imaging and single-photon emission computed tomography were performed at 2-6 h and 20-24 h postinjection. Human anti-mouse antibody levels were determined before injection and at 2 and 6 weeks. RESULTS: In 4 of 15 patients (27%), the disease stage was altered in response to the scintigraphic findings. The physiologic biodistribution of the antibody demonstrated splenic uptake caused by antibody targeting of the white pulp and of normal B-cells, and renal uptake caused by urinary excretion. Lymph node and bone marrow involvement of known tumor sites were clearly seen. A number of previously unknown tumor sites were revealed by LL2-radioimmunodetection despite normal morphologic imaging results. Long-term follow-up of these patients is required to verify these findings. No human anti-mouse antibody elevations or adverse reactions were found in the patients studied. CONCLUSION: These preliminary data suggest that Tc-99m-labeled LL2 Fab' yields useful clinical results, especially for the staging of patients with NHL before initial therapy or for the detection of early disease recurrence.

Animals↗
PubMed1994

Reversal of chemoresistance in malignant gliomas by calcium antagonists: correlation with the expression of multidrug-resistant p-glycoprotein.

Resistance to multiple drugs is often observed in malignant gliomas. The authors used a microtiter tetrazolium test to analyze primary in vitro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 micrograms/ml (1,4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU), 50 micrograms/ml cisplatin, 1 microgram/ml vincristine, or combinations of these chemotherapeutic agents. Primary chemoresistance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on paraffinized tumor sections. Eight of 15 specimens (53%) showed positive staining for the monoclonal antibody. Primary chemoresistance was overcome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0.01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p-glycoprotein, addition of calcium antagonists to the cell cultures did not influence primary chemoresistance. It is concluded from these data that addition of calcium antagonists to the adjuvant chemotherapy of malignant gliomas might overcome primary chemoresistance in tumors expressing the multidrug-resistant phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Immunoscintigraphy of carcinomas in the area of the head-neck with technetium-99m marked monoclonal antibody 174H.64. A new diagnostic procedure].

Twenty-one patients with squamous cell carcinomas of the head and neck were studied by immunoscintigraphy and immunoemission, computed tomography (ECT) using monoclonal antibody 174H.64 (Biomira Edminton) labelled with 99Tcm (Schwartz Method). Immunoscintigraphic results were compared with routine clinical assessments, including CT and ultrasonography, and were controlled by histopathological examination after surgery. All primary localizations (pT1 = 3, pT2 = 3, pT3 = 7, pT4 = 5; oropharynx 7, larynx 5, hypopharynx 3, oral cavity 3, lymph nodes 3) could be visualized, while 15 out of 18 neck lesions from tumor metastases could also be visualized (pN1 = 8, pN2 = 8, pN3 = 2). In one case with micrometastases in lymph nodes that could not be demonstrated by other methods, staging was upgraded by the immunoscintigraphic results. Three other micrometastases in lymph nodes could not be visualized. Distant metastases were suspected in 5 cases, three of which were confirmed either histologically or by radiography. Two of the cases with distant metastases were detected by the immunoscintigraphy. The present results indicate that immunoscintigraphy in combination with immuno-ECT can improve preoperative staging of head and neck carcinomas, especially with regard to metastatic neck disease, tumor recurrences and some cases of distant metastases.

Antibodies, Monoclonal↗
PubMed1993

A novel technetium-99m labeled monoclonal antibody (174H.64) for staging head and neck cancer by immuno-SPECT.

A novel murine monoclonal antibody (MAb 174H.64) was labeled with 99mTc by a direct method. MAb 174H.64 detects a cytokeratin-associated antigen which is expressed by over 90% of all squamous cell carcinomas. Panendoscopy, sonography and computerized tomography scan were performed in all cases as well as magnetic resonance imaging (in selected patients). Pre-operative immunoscintigraphy was performed in 21 patients with histologically proven primary carcinomas (18 with remaining primary tumors and 3 with lymph node recurrences). Scintigraphic images were obtained 4-6 h after injection of 1.1 GBq of the 99mTc-labeled antibody (2 mg). Late images were acquired 18 to 24 h after injection. Single-Photon-Emission-Computed Tomography (SPECT) of the head and thorax was performed in all patients. The primary tumors were immunoscintigraphically visualized in all 18 patients with remaining primary tumor. Fifteen of 18 loco-regional lymph node metastases were visualized by immunoscintigraphy (the smallest lesions had a diameter of < 1 cm), in one patient lymph node metastases were detected by immunoscan only. Two metastatically involved lymph nodes were identified by histology only (micrometastases). Distant metastases were present in 3 patients, of which two were identified by immunoscintigraphy. Immuno-SPECT according to this method was a sensitive and specific imaging modality for preoperative staging of patients with squamous cell carcinoma of the head and neck and detected lymph node metastases with higher accuracy than conventional clinical and imaging modalities.

Animals↗
PubMed1993

[Diagnosis of thrombosis with a murine anti-thrombocyte antibody (99mTc-BW 4): initial clinical results].

The high incidence of deep venous thrombosis requires for successful therapy a timely and accurate diagnosis. We report early clinical results with a 99mTc-labelled anti-platelet antibody (BW 4) for the diagnosis of thrombosis or for studying platelet kinetics. 10 patients were studied of whom 7 were imaged for the detection of thrombi. 3 deep venous thromboses were diagnosed. 3 patients were sent for diagnosing pathological platelet kinetics; 2 demonstrated a markedly changed platelet biodistribution (increased spleen uptake compared to thrombosis patients). The simple and safe handling of the labelling kit enables early studies (within 30 min). The short physical half-life of 99mTc allows a favourable target (thrombus) to non-target (blood-pool) ratio for diagnosis within 2-6 h after injection. Human anti-mouse antibodies were not found in the serum of 4 patients (blood drawn until 4 weeks after administration). There were no side effects.

Adolescent↗
PubMed1992

Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography.

HMPAO-single photon emission computerized tomography (SPECT) is a useful technique in studying cerebral blood flow (CBF). This method is suitable to evaluate the differences of CBF with reference to total sleep deprivation (TSD) within 24 h because of the short half-life of the radiopharmaceutical compound. In the present study, CBF before and after TSD was analysed in patients suffering from major depression. The morning before and after TSD, Tc-HMPAO-SPECT was performed in 20 patients. Hamilton Rating Scale for Depression scores and subjective ratings were obtained daily. Eleven patients responded to TSD; 9 were nonresponders. The main finding was a significant left temporal and mainly right parietal increase of CBF, which was observed in the responders only. CBF values and the severity of depression correlated inversely.

Adult↗
PubMed1990

Immunoscintigraphy using a technetium-99m labelled monoclonal anti-CEA antibody in the follow-up of colorectal cancer and other tumours producing CEA.

Using the intact monoclonal IgG1 anti-CEA antibody BW 431/26 (Behringwerke Marburg, FRG) labelled with 99mTc by a new labelling procedure (Schwarz method), 72 patients suspected of tumour recurrences (colorectal cancer, n = 59) and with rising serum carcinoembryonic antigen (CEA) levels were studied. Sixty-nine of 72 studies had a positive result by immunoscintigraphy of which 52 have since been proven histologically/clinically. In six patients only immunoscintigraphy revealed a tumour recurrence while all other diagnostic modalities were negative. Of 52 studies 46 were true positive (diagnostic sensitivity 88%). In this series there was one false positive result. About one-third of all patients injected with the antibody developed a human anti-mouse response (HAMA), but no severe side effects were seen even after four applications. For the follow-up of colorectal and other CEA positive adenocarcinomas this 99mTc-labelled monoclonal antibody seems to be very promising in patients with rising serum CEA, especially if conventional diagnostic imaging procedures remain negative.

Antibodies, Monoclonal↗
PubMed1990

[The clinical relevance of human anti-mouse-antibody (HAMA) in immunoscintigraphy].

Murine monoclonal antibodies (MAb) are applied on a growing scale in radioimmunoscintigraphy (IS) for diagnostic and therapeutic purposes. This increasing use of xenogeneic substances in rapidly growing numbers of patients raises questions of accuracy and reliability of the MAb and also the problem of potential human immunoreaction (human anti-mouse IgG antibodies--HAMA). The aim of this study was to evaluate the clinical relevance of HAMA following IS regarding allergic complications and in vivo effects on IS after repeated applications of MAbs. Out of over 800 immunoscintigraphic examinations performed during the last 5 years in our department 289 studies (in 190 patients) with up to 10 applications (13 different MAbs all together) were considered. Only 1 patient with a high HAMA titer developed a mild allergic reaction (local urticaria) after the 3rd application of an anti-CEA MAb. In 171 intensively documented serum courses following IS, 50 (29%) showed elevated HAMA [1st application: 25/108 (23%); 2nd application: 20/41 (49%): 3rd application: 5/11 (45%); 4th-10th application: no HAMA/11 (2 anti-CEA, 9 Antimyosin)]. Only with strongly increased HAMA values (five times the value before 1st application) there was an altered biodistribution of the MAbs in IS with partially inhibited (8/25 studies with repeated applications) tumor localization. Some patients still demonstrated positive tumor localization despite a HAMA reaction. The problem of HAMA in the diagnostic work-up using MAbs is not the allergic reaction but the potential effects on IS in repeated studies. HAMA should be measured prior to repeated immunoscintigraphic studies.

Animals↗
PubMed1990

Tumour imaging of bladder carcinomas and their metastases with 111indium-labelled monoclonal anti-CEA antibody BW 431/26.

Fifty-one patients with muscle-infiltrating bladder carcinoma (T2-T4, N0-3, M0-1) were studied with a new imaging technique using murine monoclonal antibody directed against the carcinoembryonic antigen (CEA). A total number of 67 investigations were performed. The intact 111indium-labelled antibody (BW 431/26, Behringwerke Marburg) detected 86% of primary tumours, 93% of local and 75% of distant metastases whether there was an elevated CEA level in serum or not. Immunohistologically (avidin-biotin-peroxidase method) positive frozen tissue sections from tumour biopsies stained with the same monoclonal anti-CEA antibody, thus confirming the presence of the CEA antigen in vitro. The method was of much higher sensitivity in detecting even very small metastases than X-ray computed tomography (86% versus less than 30%). The specificity was in the region of 90%. The response to chemotherapy (MVEC regimen) was shown by repeated studies demonstrating reduced uptake (partial remission) or no accumulation (complete remission) in the second immunoscan. We suggest immunoscintigraphy of bladder tumours and their metastases as an additional method in preoperative staging and postoperative care.

Antibodies, Monoclonal↗
PubMed1989

99Tcm-labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results.

Twenty patients with malignant carcinoembryonic antigen (CEA)-producing tumour recurrences (colorectal n = 14; breast, lung, medullary thyroid carcinoma n = 2, each) were studied by immunoscintigraphy using an intact monoclonal anti-CEA antibody (BW 431/26) labelled with 99Tcm by a new labelling technique (Schwarz Method). This novel approach allows an almost quantitative labelling of the antibody, which is first reduced using a thiol, lyophilized in purified form, and then reacted with a stannous salt component before 99Tcm-pertechnetate binding. The labelling efficiency (as controlled by TLC) was greater than 95%, the in vitro stability at least 6 h. The imaging results (planar and SPECT) yielded a sensitivity of 91%, a specificity of 87% and a diagnostic accuracy of 90%. These first promising clinical results trigger the hope that the successful labelling of monoclonal antibodies with 99Tcm is a decisive step towards the more practically orientated use of tumour immunoscintigraphy.

Adult↗
PubMed1989

[Successful immunoscintigraphic tumor detection with technetium 99m marked monoclonal anti-CEA antibodies].

Twenty patients aged 32-76 years (median 56 years) with various primary cancers or tumor recurrences (colorectal n = 14; lung, breast, medullary thyroid carcinoma n = 2, each) were studied with a technetium-99m labeled anti-CEA antibody. Intact monoclonal antibody BW 431/26 (Scintimum CEA-Tc-99m, Behringwerke AG, Marburg) was successfully labeled (Schwarz Method) by an instant 2-vial kit (labeling efficiency greater than 95% (TLC, HPLC), preserved immunoreactivity). The most frequent clinical indications were (1) the detection of tumor recurrences in patients with a steadily increasing serum CEA level (at a mean 2.3 years after complete removal of the primary tumor) but normal findings by conventional imaging modalities, (2) the search for extrahepatic tumor involvement in patients with known liver metastases scheduled for regional chemotherapy. Gamma camera scintigrams (planar and ECT) were performed 6-12 h and 18-26 h postinjection yielding a sensitivity of 95% (positive tumor contrast in 19/20 patients) with a specificity of 90% (positive predictive value 95%). Immunoscintigraphy successfully depicted tumor recurrences in 4/6 patients with elevated serum CEA values where all conventional imaging modalities had failed. The successful labeling of monoclonal antibodies with 99mTc represent an important step in clinical progress for the more practically orientated use of immunoscintigraphy and also opens new diagnostic fields.

Adult↗
PubMed1989

[Immunoscintigraphy with radionuclide-labeled monoclonal antibodies for tumor diagnosis and in benign diseases].

Immunoscintigraphy using radiolabeled (technetium-99m, indium-111, iodine-131) monoclonal antibodies is successfully (sensitivity over 80%, specificity over 90%) applied since some years in the clinic for the detection of CEA- and or CA 19-9-producing colorectal and CA 125-positive ovarian carcinoma recurrences and just recently for the diagnosis of benign diseases (myocardial infarction/transplant rejection/thrombosis/abscess localization.

Abscess↗
PubMed1987

[Echocardiography findings before and following beta-irradiation (106Ru/106Rh) of choroid melanoma].

Echographic follow-up examinations were performed in 72 patients in whom a choroidal melanoma was treated with (106Ru/106Rh) applicators. The observation period was between 6 and 15 months. Echographic measurement of tumor prominence and assessment of the degree of reflection proved to be important indicators for judging the success of beta radiation therapy. If the prominence diminishes and the degree of reflection increases after treatment, regression of the tumor may safely be assumed to have occurred. Apart from an increase in the prominence of the tumor, a constantly low or even falling level of reflection are signs of a less favorable prognosis.

Choroid↗