Labeling Monoclonal Antibody with α-emitting At at High Activity Levels via a Tin Precursor.

In a previous clinical study, the authors evaluated the potential of antitenascin C monoclonal antibody (mAb) 81C6 labeled with At via the prosthetic agent -succinimidyl 3-[At]astatobenzoate (SAB) for the treatment of primary brain tumors. Although encouraging results were obtained, labeling chemistry failed while attempting to escalate the dose to 370 MBq. The goal of the current study was to develop a revised procedure less susceptible to radiolysis-mediated effects on At labeling that would be suitable for use at higher activity levels of this α-emitter.

Radiopharmaceutical chemistry of targeted radiotherapeutics, part 4: Strategies for At labeling at high activities and radiation doses of At α-particles.

Introduction: Alpha particles are radiation of high energy and short range, properties that can lead to radiolysis-mediated complications in labeling chemistry at the high radioactivity levels required for clinical application. In previous papers in this series, we have shown that radiation dose has a profound effect on the astatine species that are present in the labeling reaction and their suitability for the synthesis of N-succinimidyl 3-[At]astatobenzoate. The purpose of this study was to evaluate the effects of adding N-chlorosuccinimide (NCS) to the methanol solution used for initial isolation of At after distillation, a process referred to as At stabilization, on At chemistry after exposure to high radiation doses.

Engineered modular recombinant transporters: application of new platform for targeted radiotherapeutic agents to alpha-particle emitting 211 At.

Purpose: To generate and evaluate a modular recombinant transporter (MRT) for targeting 211 At to cancer cells overexpressing the epidermal growth factor receptor (EGFR).

Methods And Materials: The MRT was produced with four functional modules: (1) human epidermal growth factor as the internalizable ligand, (2) the optimized nuclear localization sequence of simian vacuolating virus 40 (SV40) large T-antigen, (3) a translocation domain of diphtheria toxin as an endosomolytic module, and (4) the Escherichia coli hemoglobin-like protein (HMP) as a carrier module. MRT was labeled using N-succinimidyl 3-[211 At]astato-5-guanidinomethylbenzoate (SAGMB), its 125 I analogue SGMIB, or with 131 I using Iodogen.

Targeted alpha-particle radiotherapy with 211At-labeled monoclonal antibodies.

An attractive feature of targeted radionuclide therapy is the ability to select radionuclides and targeting vehicles with characteristics that are best suited for a particular clinical application. One combination that has been receiving increasing attention is the use of monoclonal antibodies (mAbs) specifically reactive to receptors and antigens that are expressed in tumor cells to selectively deliver the alpha-particle-emitting radiohalogen astatine-211 (211At) to malignant cell populations. Promising results have been obtained in preclinical models with multiple 211At-labeled mAbs; however, translation of the concept to the clinic has been slow.

Radiopharmaceutical chemistry of targeted radiotherapeutics, Part 3: alpha-particle-induced radiolytic effects on the chemical behavior of (211)At.

Unlabelled: Two characteristics of alpha-particles that enhance their potential for targeted radiotherapy are their high energy and approximately cellular range. Unfortunately, these properties also can have negative consequences, confounding the production of clinically relevant levels of radiopharmaceutical because of radiolytic effects. The purpose of this study was to evaluate the effect of radiation dose on the astatine species present before initiation of a labeling reaction and the potential role of these molecules in the efficiency of N-succinimidyl 3-(211)At-astatobenzoate (SAB) synthesis.