Targeting hard-to-kill fungal infections

Killing the disease without killing the patient is an old dilemma for doctors fighting cancer and some of the tougher microorganisms such as fungal infections in individuals with suppressed immune systems. Drugs have little effect when a patient’s own immune system isn’t available to help, and these fungi can resist external radiation that would kill even a perfectly healthy human. But they can be easily killed by a very small dose of radiation inside their cells.

Monoclonal antibodies can be designed to deliver radiation to specific cell types while sparing surrounding tissue. These designer antibodies, armed with radioactive isotopes, have been found to be highly effective against some types of cancer, but the combination may also be useful in other types of serious disease. This technique is known as radioimmunotherapy (RIT).

A study appearing in the February issue of The Journal of Nuclear Medicine demonstrates that radioimmunotherapy (RIT) provides a new, highly effective way to kill Cryptococcus neoformans and Histoplasma capsulatum, the fungi responsible for fungal meningitis and pneumonia, using much smaller levels of radiation than required to kill the fungi by external radiation. The study used organism-specific monoclonal antibodies coupled with radioactive isotopes of bismuth or rhenium.

“Our results demonstrate that particulate radiation delivered by organism-specific radiolabeled antibodies is orders of magnitude more efficient in killing human pathogenic fungi than external gamma radiation,” stated lead investigator Ekaterina Dadachova of the Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx. “The results provide strong experimental support for the concept of using RIT as a method to target not only fungal infections but also other microorganisms – especially multi-drug resistant ones.”

Susceptibility of the Human Pathogenic Fungi Cryptococcus neoformans and Histoplasma capsulatum to ã-Radiation versus Radioimmunotherapy with á- and â-Emitting Radioisotopes was written by Ekaterina Dadachova, PhD, Ruth A. Bryan, PhD and Annie Frenkel, BA, from the Department of Nuclear Medicine; Joshua D. Nosanchuk, MD from the Department of Medicine; Arturo Casadevall, MD, PhD, from the Departments of Medicine and Microbiology and Immunology; all from the Albert Einstein College of Medicine, Bronx, NY and Roger W. Howell, PhD, from the Department of Radiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ.

Copies of the article and an image related to the study are available to media upon request to Gavin McDonald. Current and past issues of The Journal of Nuclear Medicine can be found online at jnm.snmjournals.org. Print copies can be obtained at $15 per copy by contacting the SNM Service Center, Society of Nuclear Medicine, 1850 Samuel Morse Drive, Reston, VA 20190-5315; phone: (703) 326-1186; fax: (703) 708-9015; email: servicecenter@snm.org. A yearly subscription to the journal is $210 for individuals and $318 for institutions. A subscription is a Society of Nuclear Medicine member benefit.

The Society of Nuclear Medicine is an international scientific and professional organization of more than 14,000 members dedicated to promoting the science, technology, and practical applications of nuclear medicine. The SNM is based in Reston, VA.