Interstitial photodynamic therapy with the second-generation photosensitizer bacteriochlorin a in a rat model for liver metastases.
Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective in tumour destruction upon illumination with light of a wavelength of 760 nm. Tissue penetration by light at this wavelength is greater compared with wavelengths at which commonly used photosensitizers are illuminated, making it possible to treat larger tumours. In a model of experimental liver metastases in rats, we measured lesion sizes after interstitial illumination of tumours at different times after intravenous administration of BCA (10 mg kg(-1) bodyweight), as well as BCA concentrations in liver and tumour tissue. In both, BCA concentrations showed a rapid decline within the first 4 h, followed by a slow decrease over the next 20 h, suggesting biphasic pharmacokinetics. No selective uptake in tumour tissue was observed. A near-linear relationship was found between lesion sizes and liver and tumour BCA concentrations, suggesting that optimal results with photodynamic therapy (PDT) could be obtained by illumination within a short time interval after administration, when tissue concentrations are highest. No severe liver toxicity was observed as indicated by serum ALAT levels. However, in all tumours evaluated, islands of vital-looking cells were present leading to tumour regrowth within 35 days. In view of the obtained lesion diameters of approximately 13 mm after BCA-PDT and the rapid clearance rate of BCA, the concept of a near-infrared absorbing photosensitizer for PDT of liver tumours is a potential interesting strategy.
Rovers
J P
JP
Department of Surgery, Leiden University Medical Centre, The Netherlands.
Schuitmaker
J J
JJ
Vahrmeijer
A L
AL
van Dierendonck
J H
JH
Terpstra
O T
OT
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D017319:Photosensitizing Agents; D011166:Porphyrins; C065423:bacteriochlorin a