A comparison of functional bladder damage after intravesical photodynamic therapy with three different photosensitizers.
The influence of type of photosensitizer, drug and light dose, and time interval between photosensitizer and illumination on the extent of photodynamic therapy (PDT)-induced bladder damage and recovery was investigated using a mouse model. The three photosensitizers studied were Photofrin, meso-tetrahydroxyphenylchlorin (m-THPC) and bacteriochlorin a (BCA). Functional bladder damage was quantitatively assessed from increases in urination frequency index (FI) at 1-35 weeks after illumination and histological damage was qualitatively assessed at 1 day, 1, 2 and 12 weeks. Photofrin-mediated PDT caused an acute increase in FI at 1 week, with recovery within 2-8 weeks after light doses of 2.7-8.2 J/cm2. After higher light doses there was only partial recovery. Previous results indicated that the acute response and rate of recovery was the same whether Photofrin was given at 1 day or up to 7 days before illumination. The m-THPC-mediated PDT at drug doses of > or = 0.3 mg/kg also resulted in a marked acute response with good recovery, even after 10.8 J/cm2. Lower drug doses in combination with 5.4 J/cm2 did not result in acute or late damage. There was no significant difference in acute response when m-THPC was given 1, 3 or 7 days before illumination, although recovery was faster for the longer illumination intervals (3 or 7 days). Illumination at 1 h after 20 mg/kg BCA induced an acute response within 2 days after illumination, with recovery within 4-8 weeks. Lower drug doses did not result in damage. The most prominent histological changes during the acute period with all three photosensitizers were submucosal edema and vessel dilation, with epithelial denudation (depending on drug/light dose). We conclude that BCA and m-THPC are both potent new photosensitizers. They can induce a moderate to severe acute bladder response with complete healing over a period of a few weeks. The photosensitizer m-THPC is very effective with low doses of photosensitizer and light, whereas relatively high doses of BCA and light are required to obtain equivalent functional bladder damage in our mouse model.
Post
J G
JG
Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam.
te Poele
J A
JA
Schuitmaker
J J
JJ
Stewart
F A
FA
D000283:Administration, Intravesical; D000818:Animals; D005260:Female; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000633:toxicity*; D011833:Radiation Injuries, Experimental / Q000209:etiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000209:etiology*
D017319:Photosensitizing Agents