Biodistribution of hypericin in orthotopic transitional cell carcinoma bladder tumors: implication for whole bladder wall photodynamic therapy.
In a recent clinical study, we reported a selective uptake of hypericin in superficial bladder tumors. The results suggested that hypericin, a potent photosensitizer, could be used not only for diagnosis but also for photodynamic therapy (PDT) of superficial bladder tumors. In the present study, we investigated the biodistribution of hypericin in an orthotopic rat bladder tumor model by assessing the extent of hypericin penetration and the kinetics of accumulation into rat bladder tumors and normal bladder wall. Hypericin (8 or 30 microM) was instilled into the bladder via the catheter for 1, 2 or 4 hr. The fluorescence of hypericin in the bladder tumors and normal bladder was documented using fluorescence microscopy. In situ quantification of hypericin fluorescence in the tumor or normal bladder was performed using the laser-induced fluorescence technique. There was much more hypericin fluorescence in the tumor than in the normal bladder, with the tumor-to-normal-bladder ratio mounting to 12:1 after 4 hr of hypericin (30 microM) instillation. Moreover, hypericin was retained in the tumor for at least 1 hr before it was gradually lost from the tissue. Microscopically, the fluorescence of hypericin was restricted to the urothelial tumor and normal urothelium without fluorescence in the submucosa and the muscle layers. Subsequently no hypericin was detected in plasma, indicating that under these conditions systemic side effects should not be expected. Because the conditions used in this study were similar to those used in our previous clinical study, it is therefore likely that whole bladder wall PDT in the clinic under these conditions will produce selective urothelial tumor destruction without causing damage to the underlying muscle layers.
Kamuhabwa
Appolinary A R
AA
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Van Evenstraat 4, B-3000 Leuven, Belgium.
Cosserat-Gerardin
Isabelle
I
Didelon
Jacques
J
Notter
Dominique
D
Guillemin
François
F
Roskams
Tania
T
D'Hallewin
Marie-Ange
MA
Baert
Luc
L
de Witte
Peter A M
PA
D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D005260:Female; D023421:Models, Animal; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D000873:Anthracenes; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin