"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.
Abstract: C. Friesen, B. Koop, G. Glatting and S.N. Reske, Nuclear Medicine, University Ulm, Germany; K..M. Debatin, Children's Hospital, University Ulm, Germany; K. Schwarz, Transfusion Medicine, University Ulm, Germany; and A. Morgenstern and C. Apostolidis, Institution for Transurane, Karlsruhe, Germany, "Overcoming Chemoresistance and Radioresistance in Leukemia Cells Using Bi-213 Labeled Anti-CD45 Monoclonal Antibody," SNM's 53rd Annual Meeting, June 3–7, 2006, Scientific Paper 125.
SNM is holding its 53rd Annual Meeting June 3–7 at the San Diego Convention Center. Research topics for the 2006 meeting include molecular imaging in clinical practice in the fight against cancer; the role of diagnostic imaging in the management of metastatic bone disease; metabolic imaging for heart disease; neuroendocrine and brain imaging; new agents for imaging infection and inflammation; and an examination of dementia, neurodegeneration, movement disorders and thyroid cancer.
SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed journal in the field; host the premier annual meeting for medical imaging; sponsor research grants, fellowships and awards; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced--and continue to explore--biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org.
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