Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model

Abstract

Summary The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection was investigated in a tumour recurrence model, using rat mammary adenocarcinoma BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21 days of growth. Immediately after removal, the operation site was exposed to 320-450 nm light of 0.1 W cm2 and 60 J cm-2 after photosensitisation with either Photofrin (5 mg kg-' i.v. 48 h before illumination) or 5-aminolaevulinic acid (ALA) (2mg ml-' in drinking water for 9 days). Porphyrin concentrations were measured in tissue samples. After 28 days, animals treated with adjunctive PDT had a significantly longer tumour-free interval than controls (P<0.01); median 25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT groups significantly fewer rats had lymph node metastasis. A porphyrin concentration ratio between tumour and mammary tissue of 2:1 was found after Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative PDT may be a safe and effective method of destroying residual tumour, thereby preventing locoregional tumour recurrence.

Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model

“…Figure 3B displays the uptake of (Ris et al, 1993;van Geel et al, 1995;van Hillegersberg et al, 1995;Mlkvy et al, 1996), we could demonstrate a significantly higher uptake of m-THPC and 5-ALA in glioma tissue than in normal brain; furthermore, we could find that levels of these substances are also higher in tissue adjacent to the tumour, however the higher uptake of m-THPC did not reach statistical significance. As is well known, malignant glial tumours have a tendency to infiltrate into the surrounding brain tissue (Burger, 1990); this infiltration has also been demonstrated for Sprague-Dawley rats, which we used in our study (Chicoine and Silbergeld, 1995 Figure 1 demonstrates the dependence of transmittance on excitation wavelength in human tissue.…”

“…Most treatment failures are due to local recurrence. PDT as a local therapy can avoid recurrences in other malignant tumours (Cairnduff et al, 1994;Jocham, 1994;Szeimies and Landthaler, 1995;van Hillegersberg et al, 1995).…”

Preclinical evaluation of 5‐aminolevulinic acid‐based photodynamic therapy for canine transitional cell carcinoma

“…Although we did not evaluate the conversion of ALA to PpIX in spontaneous canine TCC, the evaluation of human TCC revealed a 10‐fold increase in tumour PpIX fluorescence when compared with the normal urothelium (Datta et al ., 1998), suggesting that ALA‐based PDT will be a highly selective treatment for canine TCC. Because similar ALA‐induced PpIX fluorescence tumour : normal skin ratios have been reported in a spontaneous squamous cell carcinoma in a cat (Lucroy et al ., 1999), in various murine epithelial tumours (Bedwell et al ., 1992; van Hillegersberg et al ., 1995; Regula et al ., 1995) and in other human epithelial tumours (Kennedy et al ., 1996; Peng et al ., 1997), it is likely that canine TCC will behave similarly.…”

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

“…It utilizes localized photosensitizer (PS) molecules at the targeted tissue that is activated with visible light and subsequently results in the photodamage and destruction of tumor tissues . Unlike chemotherapy or radiotherapy, PDT is non‐specific to the kind of tumor and can be performed multiple times with no cumulative toxic effects …”

“…[1][2][3] Unlike chemotherapy or radiotherapy, PDT is non-specific to the kind of tumor and can be performed multiple times with no cumulative toxic effects. [4] PSs are molecules that absorb energy from the incident light source and transfers the energy to molecular oxygen which is converted to an activated form of oxygen called singlet oxygen (SO). The singlet oxygen is highly electrophilic, capable of oxidizing biological electron rich double bonds and is associated with the cytotoxicity involved in PDT.…”