SBIR-STTR Award

Photodynamic Therapy, PDT, is undergoing extensive basic, preclinical and clinical development and testing for the localization and treatment of cancer. The light source used for activating the drug in preclinical and clinical PDT trials has been the argon pumped dye laser. The dye laser is tuneable, but its reliability is low. The overall efficiency of the present PDT argon/dye laser systems is extremely low, which makes it unreliable. This has led to frustration for the PDT researchers and clinicians.It is proposed to develop a solid state laser to meet the requirement of a efficient and reliable light source to match the need of some of the new photosensitizing drugs being developed and tested for PDT. These new drugs, metallopurpurins and some chlorin compounds, have relatively broad absorption bands in the 660 (+/-20)nm region of the red spectrum which makes them potentially good clinical PDT drugs.Using a second harmonic generating crystal, KTP or BBO, it is possible to generate 659nm laser light using a Nd:YAG laser operating at 1318nm. Such a system would be significantly more efficient than an argon/dye laser. A a totally solid state laser it would also be much smaller and more reliabl than the presently used argon/dye lasers. In Phase-I of this project a doubled Nd:YAG laser operating at 659nm will be assembled using a commercially available Nd:YAG laser. Performance of this system will be quantified and preliminary testing in a mouse tumor model will be done wit the Medical College of Ohio. In Phase-II a prototype system will be developed for use in precinical and clinical trials of PDT using these new photosensitizers.National Cancer Institute (NCI)

Photodynamic therapy (PDT) is continuing to undergo a rapid expansion in basic, preclinical and clinical research, and development as a modality for the diagnosis and treatment of cancer and other nonmalignant diseases. One of the major hindrances to this development is the lack of an efficient, reliable and easy to use laser source. In addition, a great deal of development is presently underway on 2nd generation photosensitizers, PSS, with absorption deeper in the red and near infrared spectra, <1200 nm. In phase-I a red Nd:YAG laser, 659nm, was developed and tested in combination with a 2nd generation PSS in a mouse tumor model. The laser is a KTP doubled 1318nm Nd:YAG and the photosensitizer the tin-IV etiopurpurin dichloride, SnET2. Animal testing of this combination of drug and laser determined it to be a viable PDT package. In phase-II it is the objective to further develop and refine the 659nm laser and quantitate its performance with three 2nd generation PSS. This will include the conversion of an existing clinical 532nm doubled Nd:YAG laser system to 659nm operation and its expanded testing with SnET2. Additionally, testing with the aspartyl-chlorin-E6. NP-6 PSS will be done. This testing will include direct comparison to the CW argon pumped dye laser to evaluate the impact of the 659nm ND: YAG's pulsed nature. Based on the results of the animal studies and the availability of the new 2nd generation PSS for clinical studies, limited phase-I clinical trials of the 659nm laser may be undertaken in the second year of the phase-II program. This PDT system package could provide a significant improvement in both the effectiveness and useability of PDT.

Thesaurus Terms:
biomedical engineering, instrumentation clinically oriented, biomedical engineering, technology development, optics, lasers, phototherapy, laser therapy animals, chordates, mammals, rodents, myomorpha, mice (laboratory)