Biodistribution of protoporphyrin IX in rat urinary bladder after intravesical instillation of 5-aminolevulinic acid.
OBJECTIVE
Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Problems of detrusor muscle scarring and prolonged cutaneous photosensitivity with current photosensitizers may be reduced by using the new photosensitizer precursor, 5-aminolevulinic acid (ALA). We studied the fluorescence distribution of protoporphyrin IX (PpIX, the active derivative of ALA) in rat urinary bladder after intravesical administration of ALA as the first step to undertaking PDT using locally administered ALA.


METHODS
Solutions of varying concentrations of ALA and pH were given intravesically to Wistar rats. The bladder was removed 1 to 24 hours later for measurement of the tissue levels of PpIX by fluorescence microscopy in the layers of the bladder wall.


RESULTS
The stability of the ALA solution steadily decreased as the pH was increased from 2.1 to 7. The best value was pH 5.5, at which the stability of the solution and the urothelial tolerance were both acceptable. The maximum PpIX fluorescence intensity ratio between urothelium and the underlying muscle layer was 11 to 1. This was seen 5 hours after instillation of 1% ALA solution at pH 5.5. A 10% ALA solution gave higher levels of PpIX in the urothelium, but less selectivity between layers.


CONCLUSIONS
Under appropriate conditions, intravesical instillation of ALA can be used to sensitize the bladder urothelium with a ratio between urothelial and muscle concentrations of PpIX of up to 11:1.
Chang
S C
SC
National Medical Laser Centre, University College London Medical School, England, UK.
MacRobert
A J
AJ
Bown
S G
SG
D000283:Administration, Intravesical; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D008856:Microscopy, Fluorescence; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000378:metabolism*
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX