Biodistribution of 131I-labeled anti-CK8 monoclonal antibody in HNSCC in xenotransplanted SCID mice.

BACKGROUND: A new promising approach to improve the outcome of head and neck squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate filament forming protein, is shown to be de novo expressed in dysplastic lesions as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8 seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to investigate the biodistribution of a radio-labeled Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined immunodeficiency disease) mouse model. MATERIALS AND METHODS: The mAb against CK8 was labeled with (131)I and biodistribution was tested in established HNSCC xenografts in SCID mice. The biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. RESULTS: Initially, after systemic administration of (131)I-anti CK8 monoclonal antibody high activity was seen in all the organs. Over time the general activity decreased, whereas activity accumulated in the tumor. This activity decayed compared to the other tissues with a two- to threefold prolonged radioactive half-life. CONCLUSION: Specific antibody-antigen-binding is probably responsible for the prolonged radioactive half-life in the tumor and the resulting cumulative activity due to enrichment of the (131)I-anti CK8 mAb, so that Cytokeratin 8 seems to be a suitable anchor molecule for radioimmunotherapy in HNSCC.

Application methods of local anaesthetic infiltrations for postoperative pain relief in tonsillectomy: a prospective, randomised, double-blind, clinical trial.

Perioperative local anaesthetics are often used to reduce the postoperative pain in tonsillectomy. There exist three different ways of applying local anaesthetics: (1) pre-incisional peritonsillar; (2) post-tonsillectomy wound infiltration; (3) post-tonsillectomy packing with soaked gauze. The objective of the study is the evaluation of differences of pain reduction comparing the three different techniques of application. The study design mainly includes intra-individual, prospective and double-blinded. One hundred and eighty patients (3-45 years) with recurrent tonsillitis were included. The charts of 156 were eligible for analysis. Bupivacaine was applied on both sides randomized in different ways. Pain on each side was registered for 6 days on the ward by a blinded nurse. When directly compared with the other two application methods, the post-tonsillectomy injection of bupivacaine provides significantly better results during the monitored time period. Postoperative bleeding was observed in 11 (7.3%) cases without any correlation to an application procedure. No other adverse effects were observed. In conclusion, post-tonsillectomy infiltration of the wounds with bupivacaine is superior to pre-incisional infiltration technique as well as post-tonsillectomy packing of the wounds with 0.5% bupivacaine-soaked gauze swab.

Fibrinogen/LDL apheresis as successful second-line treatment of sudden hearing loss: a retrospective study on 217 patients.

BACKGROUND: Sudden sensorineural hearing loss (SSHL) may be caused by a reduction of cochlear perfusion. Cholesterol and fibrinogen negatively influence rheological properties of blood thus leading to alteration of microcirculation. Fibrinogen/LDL apheresis improves cochlear blood flow by acutely decreasing plasma cholesterol and fibrinogen. METHODS: Remission rates of 217 patients with SSHL were analysed retrospectively after single apheresis. All patients had been treated otherwise before without any improvement of hearing. We investigated data in regard to frequency of hearing loss and time between onset of symptoms and apheresis. RESULTS: 15% of all patients had complete remissions, whereas partial remissions were seen in 46%. No change of hearing threshold was seen in 33%, 2% worsened. Remission rates decreased from 70% for a time of 2 weeks between onset of SSHL and apheresis to 63% and 21% for 6 weeks and 3 months. CONCLUSION: The present study shows that apheresis was followed by complete or partial remissions in 61% of patients even as second line therapy. The window for good therapeutic success is approximately 6 weeks.

Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody.

BACKGROUND: The mortality from squamous cell carcinoma of the head and neck (SCCHN) remains high and almost unchanged throughout the last decades. Therefore, new therapeutic strategies are urgently needed. One promising approach is the application of radio-labeled antibodies directed against tumor-associated antigens. EpCAM is a transmembrane protein, which is overexpressed on almost all SCCHN, making it a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to establish an animal model to investigate the biodistribution and the therapeutic effect of a radio-labeled EpCAM-specific monoclonal antibody (mAb). MATERIALS AND METHODS: The mAb C215 was labeled with 131I and tested for its antitumor effect against established SCCHN xenografts in SCID mice. Initially, the biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. For therapeutic approaches 5, 15 or 25 MBq 131I-labeled mAb was injected as a single bolus into tumor-bearing mice. Control animals received either sodium chloride or the unlabeled mAb. The tumor growth and body weight of the animals were measured at various times after administration of the antibody. RESULTS: Initially, high activity was seen in all organs after systemic administration of 13I-C215. Over time general activity decreased whereas an accumulation of activity was seen in the tumor. Tumor growth was delayed in the groups receiving either 15 MBq or 25 MBq 131I-C215 relative to control groups and the 5 MBq group. However, animals in the high-dose groups suffered from treatment-related toxicity, which led to body weight loss of more than 20%. CONCLUSION: Our data demonstrate that the EpCAM-specific radio-labeled mAb C215 is a promising tool to target SCCHN leading to significant tumor control. Further studies are necessary to increase efficacy and reduce toxicity of this new therapeutic approach.

Limited suitability of EpCAM for molecular staging of tumor borders in head and neck cancer.

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is expressed in most normal epithelia, but is absent from squamous stratified epithelia. However, a de novo expression can be observed in squamous epithelia during carcinogenesis. MATERIALS AND METHODS: In order to evaluate EpCAM as a molecular marker to indicate borders of high risk for the development of local recurrences, its expression was examined in the marginal zone of malignancies. Specimens of squamous cell carcinoma of the head and neck (SCCHN), of the histologically tumor-free defined resection margin and of healthy epithelia of 20 patients were examined by RT-PCR in order to identify the expression of EpCAM in these three different areas. Additionally, immunohistochemistry was perfonned on biopsies from 10 patients in order to confirm these findings and to investigate a potential correlation between EpCAM expression and the degree of dysplasia. RESULTS: By RT-PCR, high expression of EpCAM was found in the tumor. An inverse correlation was observed between EpCAM expression and the distance from the tumor, with no expression being detectable in healthy oral mucosa. In 70% of the cases, EpCAM was expressed in the marginal zone, which had been defined as tumor-free by routine histopathological assessment. Additional immunohistology revealed no correlation between EpCAM expression and the grade of dysplasia. CONCLUSION: Our data provide evidence that EpCAM is restricted as a marker for redefining the real tumor margin by RT-PCR. To complement routine histology, immunohistochemical staining with EpCAM is limited due to its expression in hyperplastic tissue without dysplastic changes. Both observations limit the reliable use of EpCAM for the molecular definition of the critical tumor border and resection margins.