Photodynamic therapy of the canine prostate: intra-arterial drug delivery.
OBJECTIVE
Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model.


METHODS
To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light.


RESULTS
Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity.


CONCLUSIONS
Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.
Moore
Ronald B
RB
Department of Surgery, University of Alberta, 2D2.16 Walter Mackenzie Health Sciences Centre, 8440-112 Street, Edmonton, Alberta, Canada T6G 2B7. rmoore@cha.ab.ca
Xiao
Zhengwen
Z
Owen
Richard J
RJ
Ashforth
Robert
R
Dickey
Dwayne
D
Helps
Cathy
C
Tulip
John
J
D000818:Animals; D004285:Dogs; D005471:Fluoroscopy; D005500:Follow-Up Studies; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D023421:Models, Animal; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage / Q000378:metabolism; D011467:Prostate / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013668:Technetium Tc 99m Aggregated Albumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; C482398:QLT0074; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C044797:chloroaluminum phthalocyanine