19 July 1994 Exploitation of interstitial brachytherapy techniques for photodynamic therapy--II. Novel photosensitizeers for the treatment of solid tumors
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Abstract
The treatment of solid human tumors of volume up to 50 cm3 will require significant gains in photosensitizing effect over that obtained with Photofrin and 630 nm light. Some techniques of interstitial radioisotope brachytherapy can be exploited for the uniform delivery of laser light to solid tumor volumes. Our dosimetry planning system (T-PIPET) was used to design 7- and 9- fiber illuminators for the treatment of R3327-AT rat prostate tumors by interstitial PDT. Relatively uniform light fields within encompassed tumor volumes could be achieved with needle spacings of 0.9 and 1.2 cm for light of 670 and 750 nm, respectively. Novel photosensitizers derived from pheophorbide and bacteriopheophorbide and activated by 673 and 753 nm light, respectively, were at least 1000X more potent than Photofrin in photokilling EMT-6 tumor cells in vitro. Tumor response in vivo resulted from perfusion shutdown and secondary ischemic cell death. Complete tumor response and some cures were demonstrated when R3327-AT rat prostate tumors of 3.5-4.5 cm3 volume were treated with 400 J of 673 nm light delivered 1 hour after the i.v. administration of 2mg/kg Ph4-OH. Current studies will optimize the vehicle for drug delivery, the time between drug and light administration and the light dose uniformity required throughout a treatment volume for maximizing tumor cures. A two-fold gain in tissue penetrance by longer wavelength light combined with at least a 100X gain in in vivo effectiveness by these novel photosensitizers makes feasible the treatment of solid human tumors by interstitial PDT with current laser systems.
© (1994) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
J. Donald Chapman, J. Donald Chapman, C. C. Stobbe, C. C. Stobbe, E. L. Engelhardt, E. L. Engelhardt, Matthew C. Fenning, Matthew C. Fenning, D. Q. Brown, D. Q. Brown, A. Dagan, A. Dagan, S. Gatt, S. Gatt, } "Exploitation of interstitial brachytherapy techniques for photodynamic therapy--II. Novel photosensitizeers for the treatment of solid tumors", Proc. SPIE 2133, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III, (19 July 1994); doi: 10.1117/12.179975; https://doi.org/10.1117/12.179975
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