Photosensitization and tissue distribution studies of the picket fence porphyrin, 3,1-TPro, a candidate for photodynamic therapy.
From a structurally distinct set of o-substituted tetraphenylporphyrins, the picket fence porphyrin (PFP), 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin (3,1-TPro) has been selected as a potential candidate for use in the photodynamic therapy (PDT) of cancer. In this report, the time-dependent tissue distribution of 14C-labeled 3,1-TPro is described along with the results of various treatment regimens. The tissue distribution of radiolabeled 3,1-TPro is comparable to that of other porphyrin photosensitizers with the advantage of being most effective at 4 h and being cleared rapidly from most tissues. The results of the various treatment regimen experiments, as well as other studies, indicate that the 3,1-TPro mechanism of action is similar to that of other photosensitizers, but may include some minor differences. The conclusion is that 3,1-TPro and other PFP offer a class of effective photosensitizers that may be exploited for their structural versatility, straightforward synthesis leading to a compound of high purity and known structure, and stability (both in terms of shelf-life and in vivo metabolism) as potential candidates for PDT.
Lawrence
D S
DS
Department of Chemistry, University of Rochester, College of Arts & Science, NY 14627.
Gibson
S L
SL
Nguyen
M L
ML
Whittemore
K R
KR
Whitten
D G
DG
Hilf
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; C067903:3,1-meso-tetrakis(2-propionamidophenyl)porphyrin