Abstract
Photodynamic therapy (PDT) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue. We therefore investigated interstitial tumour illumination as a means of selective PDT. A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats. Photofrin was administered (5 mg kg-1 i.v.) 2 days before laser illumination. Tumours with a mean (+/- s.e.) diameter of 5.7 +/- 0.1 mm (n = 106, 20 days after implantation) were illuminated with 625 nm light, at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100, 200, 400, 800 or 1600 J cm-1. Control groups received either laser illumination only, Photofrin only or diffuser insertion only. Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas. Long-term effects were studied on day 36. To determine the biochemistry of liver damage and function, serum ASAT and ALAT levels were measured on day 1 and 2, and antipyrine clearance on day 1. Tumour and surrounding liver necrosis increased with light dose delivered (P < 0.001). Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals. No deterioration in liver function was found. The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage.
Highlights
Slight changes in light penetration through the tumour could be observed during Photodynamic therapy (PDT) treatment
Liver necrosis was related to light energy, ranging from 87.8 ± 9.8% at 100 J cm-' to 128.8 ± 8.3% at 1600 J cm-' (P = 0.001) (Figure 7a)
Histological examination showed tumour cell necrosis 2 days after PDT treatment and connective scar animals treated with Photofrin only compared with diffuser tissue on day 36
Summary
One hundred and eight male Wag/Rij rats (Harlan CPB, Austerlitz, The Netherlands), weighing 180-200g were used for the experiments. They had free access to rat chow and tap water. Colon adenocarcinoma CC531, a moderately differentiated and syngeneic tumour transplantable to Wag/Rij rats, was maintained subcutaneously (Marquet et al, 1984). On the day of inoculation the tumour was excised from the donor rat, cut into pieces of approximately 2 mm and kept in Hank's balanced salt solution (HBBS). Under ether anaesthesia a small midline laparotomy was performed, followed by an incision in the left lateral lobe of the liver. Laser illumination was performed 20 ± 1 days after tumour inoculation. A relaparotomy was made under anaesthesia with Hypnorm (Janssen Pharmaceutica B.V., Tilburg, The Netherlands), mg kg-' body weight i.m., and the visible diameter of the tumour was measured with sliding callipers
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