Cure of Disseminated Human Lymphoma with [Ac]Ac-Ofatumumab in a Preclinical Model.

Immunotherapies that target the CD20 protein expressed on most non-Hodgkin lymphoma cells have improved clinical outcomes, but relapse is common. We prepared Ac-labeled anti-CD20 ofatumumab and evaluated its in vitro characteristics and therapeutic efficacy in a murine model of disseminated human lymphoma. Ac was chelated by DOTA-ofatumumab, and radiochemical yield, purity, immunoreactivity, stability, and chelate number were determined.

Cure of Disseminated Human Lymphoma with [Lu]Lu-Ofatumumab in a Preclinical Model.

Although immunotherapies that target CD20 on most non-Hodgkin lymphoma (NHL) cells have improved patient outcomes, current therapies are inadequate because many cases are, or become, refractory or undergo relapse. Here, we labelled the third-generation human anti-CD20 antibody ofatumumab with Lu, determined the in vitro characteristics of [Lu]Lu-ofatumumab, estimated human dosimetry, and assayed tumor targeting and therapeutic efficacy in a murine model of disseminated NHL. CHX-A″-diethylenetriaminepentaacetic acid-[Lu]Lu-ofatumumab was prepared.

Radiochemical Quality Control Methods for Radium-223 and Thorium-227 Radiotherapies.

The majority of radiopharmaceuticals for use in disease detection and targeted treatment undergo a single radioactive transition (decay) to reach a stable ground state. Complex emitters, which produce a series of daughter radionuclides, are emerging as novel radiopharmaceuticals. The need for validation of chemical and radiopurity with such agents using common quality control instrumentation is an area of active investigation.

Improved Radium-223 Therapy with Combination Epithelial Sodium Channel Blockade.

Radium-223 dichloride ([Ra]RaCl2) is the first approved alpha particle-emitting therapy and is indicated for treatment of bone metastatic castrate resistant prostate cancer. Approximately half of the dose is absorbed into the gastrointestinal (GI) tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here, we investigate the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects.