Photodynamic therapy of a transplanted pancreatic cancer model using meta-tetrahydroxyphenylchlorin (mTHPC)

Abstract

Summary Pancreatic cancer is difficult to treat, even for tumours localized to the pancreas. Photodynamic therapy (PDT) is a non-thermal technique for producing localized tissue necrosis with light after prior administration of a photosensitizing drug and it could have a role in the local treatment of these cancers. We studied PDT in a transplanted cancer in the hamster pancreas using the photosensitizer mTHPC (metatetrahydroxyphenylchlorin). Fluorescence microscopy showed maximum levels of mTHPC in normal pancreas 2-4 days after sensitization and in tumour at 4-5 days. For PDT, animals were given 0.1 or 0.3 mg kg-' mTHPC and the tumour was treated at laparotomy 2 or 4 days later with red light (50 J at 650 nm, continuous or fractionated) delivered via a single fibre touching the tumour surface. The maximum zone of tumour necrosis (seen 3 days after PDT) was 8.7 mm in diameter with continuous irradiation, increasing to 12.4 mm with light fractionation (four equal fractions with 3 min between fractions). The main complication was sealed duodenal perforation, seen in 3 of 16 animals, probably due to inadequate shielding of the duodenum from the light. The duodenal problems seen in hamsters are unlikely to cause trouble in the much thicker human duodenum. PDT tumour necrosis in this animal model has now been shown with a range of photosensitizers, but mTHPC is attractive as it is likely to produce the largest volumes of necrosis around each treatment point with short light exposure times. This technique could have a role in the treatment of localized cancers of the pancreas in patients unsuitable for surgery and can now be considered for preliminary clinical trials.

Photodynamic Therapy Using Verteporfin Photosensitization in the Pancreas and Surrounding Tissues in the Syrian Golden Hamster

“…This malignancy has a poor prognosis and novel therapies are urgently needed. We and others have shown in a series of experimental and clinical studies of PDT that safe and efficient necrosis of pancreatic tumour tissue is possible [2][3][4][5][6] .…”

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

“…Recently, mTHPC has shown to be a very effective photosensitizer in various tumour models and clinical trials (Ris et al, 1991;Lofgren et al, 1994;Peng et al, 1995;Dilkes et al, 1996;Grosjean et al, 1996;Mlkvy et al, 1997), with possible preferential uptake in a colon carcinoma in mice compared to liver concentrations (Whelpton et al, 1995). Furthermore, mTHPC drug and light doses needed to induce tumour necrosis are much lower than that of HpD (Berenbaum et al, 1986).…”

Current Concepts in Gastrointestinal Photodynamic Therapy

“…Bile duct obstruction is another complication, but it is not as common. 127,128 This is thought to be secondary to edema of pancreatic tissue surrounding the treated area, especially near the ampulla of Vater, because it resolves spontaneously within 7 days.…”

“…The complications seen after animal treatment may be very real for human treatment as well, even though the human duodenum is thicker and the pancreas larger, making overlapping light delivery less of a concern. 127,128 Bile duct obstruction in humans could be avoided by the insertion of a biliary stent. 127,128 Further potential complications include pancreatic edema and/or pancreatitis, secondary infection of necrotic pancreatic tumor, cholangitis secondary to biliary obstruction, and even pancreatic fistula.…”

“…[122][123][124][125][126][127][128] The transition to clinical trials has not been made for a number of reasons: some are based on animal studies, and others are more theoretical. One of the most worrisome side effects in animals has been duodenal perforation.…”