Monitoring our immune system
You might be surprised to learn that there are no clinical tools to track the human immune system today. This might change soon. UCLA researchers have developed a new PET scanning probe that will allow monitoring of our immune system. The scientists have used one of the most commonly used chemotherapy drugs, gemcitabine, and slightly altered its molecular structure to create a new molecule called FAC. This new imaging technique also will help monitor response to new cancer therapies, even if it was not the initial goal. As said the lead researcher, 'this is not a cure or a new treatment, but it will help us to more effectively model and measure the immune system.' But read more...
You can see on the left how "a new PET imaging probe illuminates immune cells as it attacks infection within a mouse. Green areas indicate the presence of active immune cells." (Credit for the picture: UCLA's Jonsson Comprehensive Cancer Center). The caption comes from a Technology Review article, "Tracking the Immune System" (Jennifer Chu, June 9, 2008).
This project has been led by Owen Witte, a professor at UCLA's Jonsson Comprehensive Cancer Center and a Howard Hughes Medical Institute (HHMI) lead investigator.
Here is a description of what did the research team. They've "created the small molecule, called FAC, by slightly altering the molecular structure of one of the most commonly used chemotherapy drugs, gemcitabine. They then added a radiolabel so the cells that take in the probe can be seen during PET scanning. The probe is based on a fundamental cell biochemical pathway called the DNA Salvage Pathway, which acts as a sort of recycling mechanism that helps with DNA replication and repair. All cells use this biochemical pathway to different degrees. But in lymphocytes and macrophages, the cells of the immune system that initiate immune response, the pathway is activated at very high levels. Because of that, the probe accumulates at high levels in those cells."
And what are the results obtained with this FAC molecule? "Because the probe is labeled with positron emitting particles, cells that take it in glow 'hot' under PET scanning, which operates as a molecular camera that enables visualization of biological processes in living organisms. The work, done in animal models, will be further evaluated in subsequent studies. Eventually, Witte said, researchers hope to be able to monitor the immune systems of patients with FAC and other PET probes. 'This measurement is not invasive -- it involves a simple injection of the probe,' Witte said. 'We could do repetitive scans in a single week to monitor immune response.'"
As said another member of the research team, Caius Radu, an assistant professor of molecular and medical pharmacology who also belongs to the Crump Institute for Molecular Imaging, "What we wanted to do was to develop new ways to look inside a living organism and gather as much information as we can about the immune system. [...] We wanted to know how cells move from one site in the body to another and find a way to trace them to tumors."
For more information, this research work has been published by Nature Medicine as an advance online publication on June 8, 2008. Here is the title: Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog.
And here is the abstract. "Monitoring immune function with molecular imaging could have a considerable impact on the diagnosis and treatment evaluation of immunological disorders and therapeutic immune responses. Positron emission tomography (PET) is a molecular imaging modality with applications in cancer and other diseases. PET studies of immune function have been limited by a lack of specialized probes. We identified [18F]FAC (1-(2'-deoxy-2'-[18F]fluoroarabinofuranosyl) cytosine) by differential screening as a new PET probe for the deoxyribonucleotide salvage pathway. [18F]FAC enabled visualization of lymphoid organs and was sensitive to localized immune activation in a mouse model of antitumor immunity. [18F]FAC microPET also detected early changes in lymphoid mass in systemic autoimmunity and allowed evaluation of immunosuppressive therapy. These data support the use of [18F]FAC PET for immune monitoring and suggest a wide range of clinical applications in immune disorders and in certain types of cancer."
I could have used only some parts of this abstract, but I think the full content is more appropriate.
Sources: UCLA's Jonsson Comprehensive Cancer Center News, June 8, 2008; and various websites
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