Saturday, February 19, 2011

What can PDT does for cancer treatment?

Metastasis is the main cause of death in cancer patients. One route for the spread of metastatic cells is through tumour-associated lymphatic vessels into the lymph nodes. Affected nodes can be removed surgically along with the primary tumour, but tumour cells inside the lymphatic vessels are left behind. Now, researchers from Finland have shown how using photodynamic therapy (PDT) to destroy lymphatic vessels and the tumour cells lodged within can halt the spread of cancer (Sci. Transl. Med. 3 69ra11).

The research team – headed up by Tuomas Tammela of the University of Helsinki – used animal studies to observe the tumour metastasis process in more detail. They implanted mouse melanoma cells into mouse ears and waited up to two weeks for the tumours to reach 1–2 mm in diameter and lymphangiogenesis (the tumour-induced formation of new lymphatic vessels) to set in.

Lymphatic vessel
Immunohistochemistry revealed that the newly formed lymphatic vessels did indeed contain in-transit tumour cells, as well as small tumour nodules. Analysis of tissue sections from a patient with recurrent melanoma demonstrated that lymphatic vessels of cancer patients also contain in-transit tumour cells and nodules.

Tammela and co-workers then investigated whether PDT could selectively destroy lymphatic vessels without affecting surrounding tissue. They injected verteporfin, a photosensitive drug that's used clinically to treat macular degeneration, into the mouse ear. Fluorescence imaging revealed that the drug accumulated preferentially within the lymphatic vessels. Illumination with 689 nm laser light activated the verteporfin, causing the vessels to shrink, fragment and become leaky.

Next, the researchers examined the combination of surgery and PDT. They implanted mouse melanoma cells into the flanks of mice, and waited two weeks for the tumour cells to become established and metastasize to the axillary lymph nodes. They then injected verteporfin into the primary tumour and surrounding tissue and illuminated the entire flank with infrared laser light before surgically removing the primary tumour and lymph nodes. A control group of mice only received the surgical treatment.

Targeting intralymphatic cells
Mice that underwent surgery plus PDT showed a tumour relapse rate of around 10%, compared with 65% for mice receiving surgery alone. This finding indicates that tumour nodules in the lymphatic vessels are a source of relapse, and suggests that targeting in-transit cells may reduce the rate of cancer recurrence in human patients.

"We do not expect PDT to replace current surgical techniques, which comprise removal of the primary tumour and metastatic lymph nodes," Tammela explained. "However, PDT could easily be combined with existing surgical techniques to destroy the lymphatic vessels draining from the tumour, as well as the tumour cell aggregates residing within them." He noted that, as both and PDT are already in use in patients, they are more likely to be approved for targeting tumour-associated lymphatic vessels than drugs in earlier phases of development.

Deep treatment
One limitation of PDT is that it's constrained by the penetration of light into tissue. To evaluate the feasibility of using PDT to destroy lymphatic vessels in humans, the team examined a pig model. To reach the deeper lymphatic vessels, they injected verteporfin into the pig's hoof, and then applied laser light using a "side-fire" laser catheter inserted at the knee. Following irradiation, the pig's lymphatic vessels fragmented and became clogged, indicating that PDT can target vessels deep within the body.

"We have demonstrated that photodynamic targeting of tumour-associated lymphatic vessels and intralymphatic tumour cells prevents locoregional metastasis and eradicates routes of tumour cell dissemination via the lymphatic system," the authors conclude. "Our approach may help to eradicate microscopic tumour cell aggregates in cancer patients and should render anti-lymphangiogenic therapies more feasible for clinical application. 

By: - Research Articles 

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