Wavelength Dependence of Hematoporphyrin Derivative Photodynamic Treatment Effects on Rat Ears

Abstract

The in vivo wavelength dependence of hematoporphyrin derivative (HpD) photodynamic treatment (PDT) has been studied. Ears of 136 rats were treated at six red and four blue-green laser wavelengths (615-635, 488-514.5 nm). Hematoporphyrin derivative was administered intraperitoneally (15 mg/kg) and 24 h later both ears were irradiated, at different wavelengths, for t = 6.5, 10 or 15 min at 60 mW/cm2. Four parameters (thickness, average erythema, eschar and loss of tissue) were quantified and a combined score (CS) of effects was established statistically. The maximum combined score during follow-up was taken as a measure for the biological effect. The light distribution in rat ears during irradiation with red and blue-green light was estimated from in vivo measurements and the transport theory. Statistical analysis of the combined score data yielded values for the relative biological effectiveness (RBE). Relative biological effectiveness maxima occurred at 501.7 and 625 nm. Analyzing erythema and loss of tissue separately yielded maxima at the same wavelengths. Quantitative agreement between the latter two sets of relative biological effectiveness values was obtained only when they were referred to the actual light energy fluence in tissue, rather than to the incident fluence. These relative biological effectiveness values are about 2.3 at 501.7 nm and 1.35 at 625 nm, taking relative biological effectiveness = 1 at 630 nm.

In vivo absorption spectroscopy of tumor sensitizers with femtosecond white light

“…8(b)]. This behavior seems to confirm a saturation effect at high drug concentrations due to a filling up of the available binding sites for AlS 2 Pc within the tissue. These concentration-dependent variations in the absorption spectrum might be exploited to increase selectivity for PDT treatment.…”

“…Several researchers have demonstrated that, for a hematoporphyrin derivative (HpD) and PHOTOFRIN, the absorption spectrum, 1 the action spectrum, 2,3 and the fluorescence excitation spectrum 4 all have a maximum at 625 nm in vivo, as compared with 630 nm for the action spectrum in vitro. 5 To optimize the PDT efficacy, one would like to know the action spectrum of the photosensitizer in situ.…”

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

“…Mostly the weaker peak at 625 nm is used, as light of this wavelength penetrates deeper into the tissue (Star et al, 1990). However, in the intraoperative adjuvant application of PDT, tissue penetration may not be crucial since the tumour bulk has been removed surgically and only residual tissue of not more than millimetres in thickness has to be eliminated.…”

In vivo action spectra, absorption and fluorescence excitation spectra of photosensitizers for photodynamic therapy

“…The action spectrum for in vitro cell killing by HpD-PDT has a peak close to 630 nm [2]. However, the in vivo action spectrum for HpD-PDT (determined from damage to rat ears) has peaks close to 500 and 625 nm [3]. These wavelengths are the same as the wavelengths where the fluorescence excitation spectrum has a maximum [4].…”

“…This means that 633 nm would in principle be acceptable. Since the in vivo HpD-PDT action spectrum has a relatively narrow peak [3], PDT at 633 nm has considerably less effect than at 625 nm.…”