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

Abstract

SummaryThe only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg -1 ) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug-light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours.

Spectroscopic and molecular modeling of the binding of meso-tetrakis(4-hydroxyphenyl)porphyrin to human serum albumin

“…As one of the second-generation photosensitizers, mesotetrakis(4-hydroxyphenyl)porphyrin (THPP, Fig. 1) with high photosensitivity and organic selectivity may be used as a potential drug molecule in PDT for anticancer treatment, and indeed a recent report has shown that THPP can destroy intrahepatic tumors with better efficacies and fewer side effects [12].…”

Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

“…The selectivity of MB to tumor tissue is high and depends on a precise local injection of the dye. This study demonstrates that m-THPC is retained in an intrahepatic CRC cell tumors and that m-THPC-mediated experimental PDT is capable of inducing remission of metastatic colon tumors in the liver [115].…”

Analysis of the combined effect of lasers of different wavelengths for PDT outcome using 600, 630, and 660 nm

“…It has been considered as a promising technique for curative or palliative treatment of many different types of cancer [2].…”