Targeted closure of blood vessels

One treatment for abnormal tissue growths, including cancerous tumours, is to close off the vessels supplying blood to that region, thereby killing it off. In some parts of the body, such as the eye and the brain, this requires an extraordinary level of precision. Researchers in the UK, Canada and the US, have recently produced a photo-activated drug and demonstrated that it is able to achieve far greater precision than any existing techniques, without causing damage beyond the treated region¹.

Photodynamic therapy (PDT) involves the use of photo-sensitive chemicals administered in a drug and taken up by cells in the body. The treatment area is then irradiated by light at the wavelength necessary to cause a reaction in the PDT chemicals. With current therapies, the necessary wavelengths are such that the light is readily absorbed in the surface of the treated area; higher powers are needed to penetrate deeper, which carries the risk of thermal damage to surrounding tissue. Deeper penetration and reduced absorption in tissue outside of the treatment area, can be achieved at longer wavelengths in the near infra-red, however photons at these energies are unable to activate existing PDT drugs. The latest research shows that longer wavelengths can be used, using the principle of two photon excitation (TPE), whereby the sum of the energies from two photons is absorbed by and activates the photo-sensitive chemical.

The researchers tailored a photo-sensitive compound so that it had the necessary two photon absorption characteristics and was sufficiently reactive to destroy cells in the treated area. To demonstrate the closure of a blood vessel, they operated on 40 μm arteries in anaesthetised mice. The drug containing the compound was injected into the blood stream and a femtosecond Ti:sapphire laser (300 fs, 90 MHz, 39 mW) tuned to a wavelength of 920 nm was focused onto the artery to activate it (previous work using nanosecond lasers resulted in mainly thermal damage).

The focused laser beam was scanned across the artery for 15 minutes, causing vessel thinning and the cessation of blood flow within 12 minutes, without affecting any of the surrounding blood vessels. Examination of the closed vessel showed that there was no visible evidence of thermal damage, thus confirming that the closure was caused by the chemical damage induced by the laser.

This was the first demonstration of PDT in a living mammal, using the technique of two photon excitation. The technique offers a high degree of precision and is able to penetrate deeper into living tissue than existing methods, all without causing damage to the surrounding tissue. It may lead to improved treatments for some cancers, as well as age-related macular degeneration, which is the most common cause of blindness in old age.

1) Collins, H.A., Khurana, M., Moriyama, E.H., Mariampillai, A., Dahlstedt, E., Balaz, M., Kuimova, M.K., Drobizhev, M., Yang, V.X., Phillips, D., Rebane, A., Wilson, B.C., Anderson, H.L. (2008). Blood-vessel closure using photosensitizers engineered for two-photon excitation. Nature Photonics DOI: 10.1038/nphoton.2008.100