Enhancement of porphyrin tumor accumulation by inhibition of porphyrin liver pathway

M. Huenerbein; Hanns-joerg Sinn; Hans-Hermann Schrenk; W. Maier-Borst; E. A. Friedrich

doi:10.1117/12.136985

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5 March 1993 Enhancement of porphyrin tumor accumulation by inhibition of porphyrin liver pathway

M. Huenerbein, Hanns-joerg Sinn, Hans-Hermann Schrenk, W. Maier-Borst, E. A. Friedrich

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Proceedings Volume 1616, International Conference on Photodynamic Therapy and Laser Medicine; (1993) https://doi.org/10.1117/12.136985
Event: International Conference on Photodynamic Therapy and Laser Medicine, 1991, Beijing, China

Abstract

Photodynamic therapy has attracted attention by its potential for selective tumor destruction. However, selectivity is limited by unsatisfactory accumulation of porphyrin derivatives in tumors. Porphyrins injected intravenously are rapidly cleared from circulation by the liver. We examined the possibility of inhibiting the liver uptake of porphyrins by using the non-phototoxic hemin to compete for liver accumulation. The tumor model was an ovarian carcinoma (O-342, Zeller) transplanted in the muscle of the left hind leg of BDIX rats. To monitor the biodistribution of the photosensitizer various porphyrins were labelled with ¹¹¹Indium. The distribution of the radioactivity was imaged by a gamma camera (Phogamma IV; Searle/Siemens) and biopsies measured in a gamma counter (Berthold, Freiburg). An injection of 5 mg/kg hemin prior to introduction of the porphyrin caused competition for uptake of the photosensitizer by the liver. Consequently, the plasma half-life for all ¹¹¹Indium-porphyrins investigated was increased by 30 - 50%. The liver competition was possible both by preinjection of 5 mg/kg hemin 5 minutes before administration of the photosensitizer or by injection of hemin within 15 minutes post injection of the photosensitizer. This saturable process suggests distinct binding sites for hematoporphyrin in the liver. However, tumor uptake of the radio-labelled porphyrins was not blocked by hemin. Tumor accumulation of the porphyrins demonstrated a positive correlation to plasma retention time. Preinjection of hemin induced higher tumor uptake rates, up to a factor of 5 within 24 hours post injection. Pretreatment of the animals with hemin caused better therapeutic ratios for all porphyrins. The tumor to skin ratio of Photofrin II was raised from 4:1 to 7:1 by preinjection of hemin. This effect may be useful to reduce skin phototoxicity of PDT in man by dose reduction of the applied photosensitizers.

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M. Huenerbein, Hanns-joerg Sinn, Hans-Hermann Schrenk, W. Maier-Borst, and E. A. Friedrich "Enhancement of porphyrin tumor accumulation by inhibition of porphyrin liver pathway", Proc. SPIE 1616, International Conference on Photodynamic Therapy and Laser Medicine, (5 March 1993); https://doi.org/10.1117/12.136985

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