Exploitation of interstitial brachytherapy techniques for photodynamic therapy--II. Novel photosensitizeers for the treatment of solid tumors

摘要

Abstract: The treatment of solid human tumors of volume up to 50cm$+3$/ will require significant gains inphotosensitizing effect over that obtained withPhotofrin and 630 nm light. Some techniques ofinterstitial radioisotope brachytherapy can beexploited for the uniform delivery of laser light tosolid tumor volumes. Our dosimetry planning system(T-PIPET) was used to design 7- and 9- fiberilluminators for the treatment of R3327-AT rat prostatetumors by interstitial PDT. Relatively uniform lightfields within encompassed tumor volumes could beachieved with needle spacings of 0.9 and 1.2 cm forlight of 670 and 750 nm, respectively. Novelphotosensitizers derived from pheophorbide andbacteriopheophorbide and activated by 673 and 753 nmlight, respectively, were at least 1000X more potentthan Photofrin in photokilling EMT-6 tumor cells invitro. Tumor response in vivo resulted from perfusionshutdown and secondary ischemic cell death. Completetumor response and some cures were demonstrated whenR3327-AT rat prostate tumors of 3.5-4.5 cm$+3$/ volumewere treated with 400 J of 673 nm light delivered 1hour after the i.v. administration of 2mg/kg Ph4-OH.Current studies will optimize the vehicle for drugdelivery, the time between drug and lightadministration and the light dose uniformity requiredthroughout a treatment volume for maximizing tumorcures. A two-fold gain in tissue penetrance by longerwavelength light combined with at least a 100X gain inin vivo effectiveness by these novel photosensitizersmakes feasible the treatment of solid human tumors byinterstitial PDT with current laser systems. !20