Three-dimensional histologic validation of high-resolution SPECT of antibody distributions within xenografts.

Unlabelled: Longitudinal imaging of intratumoral distributions of antibodies in vivo in mouse cancer models is of great importance for developing cancer therapies. In this study, multipinhole SPECT with sub-half-millimeter resolution was tested for exploring intratumoral distributions of radiolabeled antibodies directed toward the epidermal growth factor receptor (EGFr) and compared with full 3-dimensional target expression assessed by immunohistochemistry.

Methods: (111)In-labeled zalutumumab, a human monoclonal human EGFr-targeting antibody, was administered at a nonsaturating dose to 3 mice with xenografted A431 tumors exhibiting high EGFr expression.

Hepatic resection for metastatic melanoma in The Netherlands: survival and prognostic factors.

Patients with hepatic metastases of melanoma have a very poor prognosis, with a median overall survival of less than 6 months. There are several small heterogeneous studies that have shown an association with prolonged survival in those patients treated with hepatic resection, but the role of surgery remains unclear. We evaluated the safety and efficacy of hepatic resection in a population-based study in the Netherlands for patients with metastatic melanoma and assessed the factors that could affect disease-free and overall survival.

A novel method to quantify IRDye800CW fluorescent antibody probes ex vivo in tissue distribution studies.

Background: We describe a new method for biodistribution studies with IRDye800CW fluorescent antibody probes. This method allows the quantification of the IRDye800CW fluorescent tracer in percentage of injected dose per gram of tissue (% ID/g), and it is herein compared to the generally used reference method that makes use of radioactivity.

Methods: Cetuximab was conjugated to both the near-infrared fluorophore IRDye800CW and/or the positron emitter 89-zirconium, which was injected in nude mice bearing A431 human tumor xenografts.

Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis.

Human cytomegalovirus (HCMV) is a widely spread herpesvirus, suggested to play a role in tumor progression. US28, a chemokine receptor encoded by HCMV, binds a broad spectrum of chemokines and constitutively activates various pathways linked to proliferation. Our studies reveal that expression of US28 induces a proangiogenic and transformed phenotype by up-regulating the expression of vascular endothelial growth factor and enhancing cell growth and cell cycle progression.

Construction and characterization of the chimeric monoclonal antibody E48 for therapy of head and neck cancer.

Data from an ongoing clinical radioimmunoscintigraphy trial indicate that 99mTc-labeled monoclonal antibody (mAb) E48 is highly capable of selectively targeting squamous cell carcinoma of the head and neck (HNSCC). The percentage of the injected dose per gram of tumor tissue was found to be high, rendering mAb E48 a promising candidate mAb for therapeutic purposes. We now describe the construction of a chimeric (mouse/human) mAb E48 by recombinant DNA technology.