Photosensitization and Tissue Distribution Studies of the Picket Fence Porphyrin, 3,1‐tpro, a Candidate for Photodynamic Therapy

Abstract

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.

Radiolabelled porphyrins in nuclear medicine

“…Quenching of the fluorescence of the hematoporphyrin species (Figure A) by body fluids, blood and normal tissue and the limited penetration depth of visible and near infrared light into tissue has restricted the development of fluorescence imaging in combination with PDT, and as such, radiolabelled porphyrins provide an alternative non‐invasive method for deep‐tumour detection, and as a means to directly assess PDT treatment progression. Indeed, early work with 3 H and 14 C radiolabelling was used to observe the specific uptake in tumours by hematoporphyrin . Hematoporphyrin and its derivatives have been radiolabelled using 99m Tc pertechnetate and stannous chloride, with radiolabelling believed to occur at the carboxylic chains of the porphyrin .…”

Structure and Biodistribution Relationships of Photodynamic Sensitizers*

“…An unusual hydrophobic sensitizer comprising one atropisomer of a "picket fence" porphyrin, 3,l -meso-tetrakis(opropionamidopheny1)porphyrin (3,l -Tpro) (37) has recently (37) been radiolabeled with I4C and studied in female Fischer rats bearing R3230AC mammary adenocarcinoma (34). A dose of 33.75 mg kg-' body weight was administered ip in Cremophor emulsion.…”

Biodistribution Assessment of a Lutetium(III) Texaphyrin Analogue in Tumor‐bearing Mice Using NIR Fourier‐transform Raman Spectroscopy¶

“…As a general rule, both normal and neoplastic tissues have been observed to retain a variety of macrocyclic photosensitizers, including hematoporphyrin derivatives (54), synthetic porphyrins (55), chlorins (2,56) and phthalocyanines (4,57), albeit with different dynamics and efficacy. Generally, in order of decreasing drug level, the following distribution is observed in normal mice tissues: liver > kidney, spleen > lung, heart > muscle ≫ brain (58–60).…”

“…There are two main approaches for the study of photosensitizer distribution in tissues. The first approach consists of two sequential steps: disintegration of the biological material in question, followed by extraction and quantitative determination of the drug in extracts by spectroscopic (UV‐Visible [Vis] absorption or fluorescence) or other (high‐performance liquid chromatography, radioactive label) analytical methods (1–3). Particularly, electronic spectroscopy, both absorption and fluorescence, is effective for the estimation of macrocyclic photosensitizers in tissue extracts because of the electronic properties of macrocycles, i.e.…”