In radioimmunotherapy (RIT), hematologic toxicity is the dose-limiting toxicity due to the long circulatory half-life of the antibody. Although intraperitoneal (i.p.) RIT results in high uptake of i.p. growing tumors, the radiolabeled antibody enters the circulation, resulting in bone marrow toxicity. Carbohydrate modification of antibodies could induce accelerated clearance of the antibody via...

INTRODUCTION Low dose-rate radioimmunotherapy (RIT) using (125)I-labelled monoclonal antibodies ((125)I-mAbs) is associated with unexpected high cytotoxicity per Gy. METHODS We investigated whether this hypersensitivity was due to lack of detection of DNA damage by the targeted cells. DNA damage was measured with the alkaline comet assay, gamma-H2AX foci and the micronucleus test in p53(-/-) ...

Cervical cancer caused by the infection with the human papillomavirus (HPV) remains the fourth leading killer of women worldwide. Therefore, more efficacious treatments are needed. We are developing radioimmunotherapy (RIT) of HPV-positive cervical cancers by targeting E6 and E7 viral oncoproteins expressed by the cancer cells with the radiolabeled monoclonal antibodies (mAbs). To investigate t...

During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabeled monoclonal antibodies and receptor binding agents. Conventional radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to low...

Non-Hodgkin's lymphoma (NHL) comprises both indolent forms, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), and aggressive forms, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). FL and DLBCL are the most common subtypes of indolent and aggressive NHL, respectively. Although these lymphomas exhibit different clinical behaviors and outcomes, th...

PURPOSE Studies herein explore paclitaxel enhancement of the therapeutic efficacy of alpha-particle-targeted radiation therapy. EXPERIMENTAL DESIGN Athymic mice bearing 3 day i.p. LS-174T xenografts were treated with 300 or 600 microg paclitaxel at 24 h before, concurrently, or 24 h after [213Bi] or [212Pb]trastuzumab. RESULTS Paclitaxel (300 or 600 microg) followed 24 h later with [213Bi]t...

Pretargeted radioimmunotherapy (PRIT) using streptavidin (SA)-conjugated antibodies (Abs), followed by clearing agent and radiolabeled biotin is a promising method that can increase the effectiveness of RIT, while decreasing the toxicities associated with directly labeled Abs. Although CD20 has been the traditional target antigen for RIT of non-Hodgkin lymphoma (NHL), studies targeting HLA DR a...

The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (131I-rituximab). Objective response was determined using ...

The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity (Srivastava, 1988; Larson, 1994). The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the effic...

Follicular lymphoma (FL) is the second most common type of nonHodgkin lymphoma [1]. The development of rituximab represented a major breakthrough in the management of FL, with several landmark clinical trials consistently demonstrating superior survival outcomes with rituximab-containing chemoimmunotherapies compared to chemotherapy alone, both in the frontline [2-5] and relapsed/ refractory se...