Athena
09-12-2008, 11:07 PM
Gene-assisted PET tracks tumour spread
Researchers at the University of California, Los Angeles (UCLA) have reported a way to track prostate-cancer cells as they ****stasize from the tumour to the surrounding lymph nodes. One particularly exciting aspect of this technique is that, in future, it could be adapted to not only locate the cancer cells, but to kill them too.
The prognosis and treatment options for prostate-cancer sufferers differ greatly, depending on whether disease is confined to the prostate capsule or has spread to the surrounding lymph nodes. Even spread on a microscopic level can make disease recurrence and progression more likely. However, the only accurate method currently available to assess lymph node involvement is surgery. There are conflicting data in the literature as to whether lymphadenectomy, the process of removing lymph nodes surrounding the prostate, helps or hinders the spread of prostate cancer.
Side-stepping the lymphadenectomy debate, the ideal scenario would involve the use of non-invasive methods to detect microscopic disease spread. And the UCLA team are looking to do just this, by developing a gene-mediated PET imaging technique that’s specific to prostate-cancer cells (Nature Med. 14 882).
Seek and destroy
The PET technique exploits a genetically engineered version of the adenovirus, better known as the common cold. This particular variant, also developed at UCLA, is prostate specific and known to transfer efficiently into the lymphatic system. The virus also contains a reporter gene (sr39tk), which transfers into the spreading cancer cells in the lymph nodes.
Once in the cancer cells, the reporter gene swings into action. The gene expression process results in a protein that can be detected via both PET and fluorescence imaging. Conventional ****bolic tracers such as 18FDG were found to be insensitive for the particular tumour model used here. Instead, 18FHBG - a known reporter of sr39tk expression in cancer cells - was used.
The UCLA researchers examined human prostate tumours implanted under the skin on the upper back of a mouse. The engineered adenovirus was injected into soft tissue around the tumour, allowing it to drain into the surrounding lymph nodes and transfer into ****static cancer cells.
Both fluorescence and PET/CT imaging demonstrated virus uptake in the axillary lymph nodes. A fluorescent marker in the tumour cells independently confirmed that microscopic spread of the tumour had indeed taken place and that ****static cells were present in the same lymph nodes.
Of course, a "real life" scenario calls for the ability to image pelvic lymph nodes (rather than axillary nodes) in situ. "The minute size of mouse anatomy and the bladder route of 18FHBG tracer excretion make it very challenging to clearly distinguish signals of the pelvic lymph nodes in whole animal scans," senior author Lily Wu told medicalphysicsweb. "Hence, we are testing the approach in dogs with prostate cancer."
Beyond developing effective imaging of ****static cells, Wu and colleagues are also seeking a means to enable targeted killing of the cells, using the multitasking gene srtk93. In addition to being a reporter imaging gene, in the presence of ’pro drug’ Gancidovir, srtk93 acts as a suicide gene. The researchers have already shown that this form of gene therapy can kill primary tumour cells (Mol. Imaging 4 463).
"Our ultimate goal is to translate the concepts described in this paper to human patients," said Wu. "We’re in the process of testing our SLN [sentinel lymph node] suicide gene therapy in several animal models, including pet dogs with spontaneous prostate cancer."
Researchers at the University of California, Los Angeles (UCLA) have reported a way to track prostate-cancer cells as they ****stasize from the tumour to the surrounding lymph nodes. One particularly exciting aspect of this technique is that, in future, it could be adapted to not only locate the cancer cells, but to kill them too.
The prognosis and treatment options for prostate-cancer sufferers differ greatly, depending on whether disease is confined to the prostate capsule or has spread to the surrounding lymph nodes. Even spread on a microscopic level can make disease recurrence and progression more likely. However, the only accurate method currently available to assess lymph node involvement is surgery. There are conflicting data in the literature as to whether lymphadenectomy, the process of removing lymph nodes surrounding the prostate, helps or hinders the spread of prostate cancer.
Side-stepping the lymphadenectomy debate, the ideal scenario would involve the use of non-invasive methods to detect microscopic disease spread. And the UCLA team are looking to do just this, by developing a gene-mediated PET imaging technique that’s specific to prostate-cancer cells (Nature Med. 14 882).
Seek and destroy
The PET technique exploits a genetically engineered version of the adenovirus, better known as the common cold. This particular variant, also developed at UCLA, is prostate specific and known to transfer efficiently into the lymphatic system. The virus also contains a reporter gene (sr39tk), which transfers into the spreading cancer cells in the lymph nodes.
Once in the cancer cells, the reporter gene swings into action. The gene expression process results in a protein that can be detected via both PET and fluorescence imaging. Conventional ****bolic tracers such as 18FDG were found to be insensitive for the particular tumour model used here. Instead, 18FHBG - a known reporter of sr39tk expression in cancer cells - was used.
The UCLA researchers examined human prostate tumours implanted under the skin on the upper back of a mouse. The engineered adenovirus was injected into soft tissue around the tumour, allowing it to drain into the surrounding lymph nodes and transfer into ****static cancer cells.
Both fluorescence and PET/CT imaging demonstrated virus uptake in the axillary lymph nodes. A fluorescent marker in the tumour cells independently confirmed that microscopic spread of the tumour had indeed taken place and that ****static cells were present in the same lymph nodes.
Of course, a "real life" scenario calls for the ability to image pelvic lymph nodes (rather than axillary nodes) in situ. "The minute size of mouse anatomy and the bladder route of 18FHBG tracer excretion make it very challenging to clearly distinguish signals of the pelvic lymph nodes in whole animal scans," senior author Lily Wu told medicalphysicsweb. "Hence, we are testing the approach in dogs with prostate cancer."
Beyond developing effective imaging of ****static cells, Wu and colleagues are also seeking a means to enable targeted killing of the cells, using the multitasking gene srtk93. In addition to being a reporter imaging gene, in the presence of ’pro drug’ Gancidovir, srtk93 acts as a suicide gene. The researchers have already shown that this form of gene therapy can kill primary tumour cells (Mol. Imaging 4 463).
"Our ultimate goal is to translate the concepts described in this paper to human patients," said Wu. "We’re in the process of testing our SLN [sentinel lymph node] suicide gene therapy in several animal models, including pet dogs with spontaneous prostate cancer."