New method of photosensitizer accumulation for photodynamic therapy in an experimental liver tumor

Abstract

A new sensitizing method of photodynamic therapy for malignant tumors and its effects was studied. Prepared for the study were pheophorbide a (Phd), dissolved in an oily contrast medium, Lipiodol (LPD-Phd), and water-soluble pheophorbide a (W-S Phd) as sensitizers, and VX-2 tumor in rabbit livers. The Phd distribution was compared after intraarterial (i.a.) administration of LPD-Phd or W-S Phd and intravenous (i.v.) administration of W-S Phd. Phd was extracted with methanol at 24 h after injection, and the supernatant absorbance was measured at 670 nm by spectrophotometry. The tumor showed higher values of Phd than did the liver with LPD-Phd i.a. and W-S Phd i.a. (P less than .01). Conversely, the tumor accumulated less Phd than did the liver with W-S Phd i.v. (P less than .05). We subsequently produced severe photo-destruction in a Walker tumor in a Sprague-Dawley rat liver with slight damage to adjacent liver tissue using LPD-Phd i.a. and Nd-YAG dye laser irradiation at 670 nm. The intraarterial administration of a photosensitizer may make it possible to treat liver tumors by photodynamic therapy.

Interstitial photodynamic therapy with the second-generation photosensitizer bacteriochlorin a in a rat model for liver metastases

“…PDT has proven to be effective in experimental tumour destruction and growth reduction within the liver, using hematoporphyrin derivative (Holt et al, 1985), Photofrin (van Hillegersberg et al, 1992), pheophorbide a (Nishiwaki et al, 1989) and aminolaevulinic acid (Svanberg et al, 1996). Nevertheless, PDT has rarely been used clinically in treatment of liver tumours, mainly because of effective accumulation of photosensitizers in liver tissue.…”

“…Because hepatic tumours are believed to be mainly supplied by blood via the hepatic artery (Ackerman et al, 1969), preferential uptake in tumour tissue could be established by injecting a photosensitizer directly into the hepatic artery (Nishiwaki et al, 1989;Purkiss et al, 1994). An additional advantage of this local administration could be reduction of systemic effects, such as skin photosensitivity.…”

Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

“…Although PDT has proven to be effective in tumour destruction within the liver using haematoporphyrin derivative (Holt et al, 1985), photofrin (van Hillegersberg et al, 1992), pheophorbide a (Nishiwaki et al, 1989) and ALA (Svanberg et al, 1996), much higher light and drug doses were needed. This is illustrated for photofrin in a liver tumour model in rats: best results were obtained at a light dose of 800 J cm -1 , with complete remission of four out of six tumours (van Hillegersberg et al, 1992).…”

Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms

“…Moreover, selective uptake of many exogenous dyes has been demonstrated in neoplastic lesions (for example see ref. 13). The use of fluorescence labeled anti-tumor antibodies also has been suggested (14).…”