Report from SNM: Antibody-labeled radiotherapy overcomes leukemia treatment resistance

June 5, 2006

A monoclonal antibody-labeled radioimmunotherapy may help overcome a leukemia resistant to radio- and chemotherapy, according to a report presented at the Society of Nuclear Medicine meeting in San Diego.

A monoclonal antibody-labeled radioimmunotherapy may help overcome a leukemia resistant to radio- and chemotherapy, according to a report presented at the Society of Nuclear Medicine meeting in San Diego.

Molecular biologist Dr. Claudia Friesen of the University of Ulm presented results Sunday showing that alpha-emitter Bi-213-labeled anti-CD45 antibody breaks resistance to radiation therapy and chemotherapy in leukemia cells by overcoming DNA repair that plays an important role in that resistance.

Targeted alpha particle radioimmunotherapy increases the dose to leukemia cells by two orders of magnitude and causes apoptosis of single-targeted leukemia cells while sparing nontarget tissues from detrimental radiation effects, Friesen said. Therapeutic efficiency is increased, and nonspecific toxicity to normal organs and tissues is decreased.

Investigations at the University of Ulm suggest targeted alpha particle therapy is much more potent than targeted beta particle or external-beam radiation therapy. Low doses of alpha particles caused prompt and complete cell death through the induction of apoptosis in sensitive and resistant tumor cells.

"Our work considerably expands options for therapeutically applied radionuclides," Friesen said. "This technique will have a wide application in many solid tumors, using suitable peptides as carriers of alpha-emitting radionuclides."

Understanding the molecular mechanisms of sensitivity and the sources of resistance of tumor cells to radiation and chemotherapeutic drugs is considered crucial to developing novel treatment options in leukemia and solid tumor therapy. The Ulm group plans to focus on identifying novel molecular targets using gene expression technologies and high-throughput techniques for synthesis and selection of high-affinity peptides as carriers of radioisotopes both for diagnostic imaging and targeted internal radiotherapy.

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