New treatment option breaks Leukemia's resistance to chemotherapy, radiation therapy

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New treatment option breaks Leukemia's resistance to chemotherapy,
radiation therapy

Published: Jun 04, 2006

German researchers provide details of targeted alpha particle therapy at
SNM's 53rd Annual Meeting June 3–7 in San Diego
SAN DIEGO, Calif.--German researchers set out to outwit cancer tumor cells
that have become resistant to chemotherapy or radiation therapy and ended
up expanding therapeutic applications of radionuclides in fighting
leukemia. This research was released at SNM's 53rd Annual Meeting June 3–7
in San Diego.

"We have found that labelling the antibody CD45 with the alpha-emitter
Bi-213 breaks resistance to radiation therapy and chemotherapy in leukemia
cells by overcoming DNA-repair, which plays an important role in
resistance," said Claudia Friesen, group leader of the laboratory of
molecular biology in the nuclear medicine department at the University Ulm
in Germany. "We provided the molecular requirements for overcoming this
resistance and for alpha particles–induced cell killing," added the
co-author of "Overcoming Chemoresistance and Radioresistance in Leukemia
Cells Using Bi-213 Labeled Anti-CD45 Monoclonal Antibody." She noted,
"Targeted alpha particle radioimmunotherapy increases the dose to leukemia
cells by two orders of magnitude and causes cell kill of single-targeted
leukemia cells--all while sparing non-target tissues from detrimental
radiation effects." With the group's approach, "therapeutic efficiency is
increased and non-specific toxicity to normal organs and tissues is
considerably decreased," she explained.

Anyone can get leukemia, a cancer of blood-forming cells; it affects
women, men and children of all ages. This cancer starts in the bone marrow
but usually spreads quickly into the blood. Over time, it may spread to
lymph nodes, the spleen, liver, the covering of the brain and spinal cord,
spinal fluid and other organs. Nearly 35,000 individuals will be diagnosed
with leukemia this year in the United States, and nearly 23,000
individuals die annually from the disease.

"New options are needed to improve therapeutic success in the treatment of
cancer, especially since tumors' resistance to chemotherapy or radiation
therapy is one of the primary causes of failure in treating the disease,"
said Friesen. "Attempts to improve the results of chemotherapy and
radiotherapy by increasing the total radiation absorbed dose, by
increasing the concentration of chemotherapeutic drugs or by changing
chemotherapeutic drugs have been only partially successful," she noted.

"The targeted alpha particle therapy is much more potent than targeted
beta particle therapy or external radiation therapy," said Friesen. Low
doses of alpha particles cause a prompt and complete cell kill in
sensitive and resistant tumor cells, researchers discovered. "Our work
considerably expands therapeutic options for therapeutically applied
radionuclides," she explained. "This technique will have a wide
application in many solid tumors, using suitable peptides as carriers of
alpha-emitting radionuclides," she continued.

"Understanding the molecular mechanisms of sensitivity and/or resistance
of tumor cells to radiation and chemotherapeutic drugs is crucial and
fundamental for the development of novel treatment options in leukemia and
solid tumor therapy. It provides the foundation for the discovery of novel
anticancer compounds and the development of methods to sensitize
previously resistant tumor cells to anti-cancer therapy," said Friesen.

Researchers will now "focus on identification of 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," said Friesen, who noted that the first clinical trial will
begin soon.

Source: Society of Nuclear Medicine's 53rd Annual Meeting

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