Photosensitizers for tumor therapy: determination of bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in rat tissue and serum by high-performance liquid chromatography.

Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a synthetic potential photosensitizer for tumor therapy. A new method, which combines solvent extraction and several purification steps, has been developed to determine its presence in tissues. Separation and quantitation of isoBOSINC is done by high-performance liquid chromatography on a silica column with toluene as a mobile phase and using fluorescence detection (lambda ex = 365 nm, lambda em = 750 nm). For recovery studies, isoBOSINC was added to muscles at levels of 0.067 and 0.67 micrograms/g; the mean recoveries were 100%, with coefficients of variation of 6.1 and 6.4%, respectively. For liver samples, the amounts added were 0.67 and 6.7 micrograms/g and for serum 0.67 and 6.70 micrograms/ml. The mean recoveries for liver were 86 and 93%, with coefficients of variation of 7.7 and 4.4%, respectively. For serum, the mean recoveries were 99 and 96%, with coefficients of variation of 2.6 and 6.9%, respectively. Due to its low detection limit and selectivity, the method is appropriate for pharmacokinetic as well as tumor uptake studies following in vivo exposure to isoBOSINC. Preliminary data on tissue distribution of the photosensitizer in normal rats are also presented.     

Treatment of Malignant Melanoma by High-Peak-Power 1064 nm Irradiation Followed by Photodynamic Therapy

Irradiation of B16 pigmented melanoma subcutaneously transplanted in C57 mice with a single 650 mj pulse (10 ns) of 1064 nm light from a Q-switched Nd: YAG laser caused instantaneous bleaching of the pigmented tissue. Visual and histological examination of the resulting gray-colored tumor revealed the breakdown of melanosomes with no detectable alteration of the normal and tumor-overlying skin. Histological examination of the irradiated tumor showed some degree of vascular damage; the depth of the photodamage was not affected by the successive delivery of three consecutive light pulses. The bleached tumor grew at a modestly slower rate but the high-peak-power (HPP) laser treatment did not affect the tumor concentration of a photodynamic sensitizer Si(IV)-naphthalocyanine (isoBO-SiNc) intravenously injected 24 h before Nd : YAG irradiation. Treatment of the B16 pigmented melanoma by photodynamic therapy (PDT: 1 mg/kg isoBO-SiNc, 300 mW/cm², 520 J/cm²) from a 774 nm diode laser immediately after the 1064 nm irradiation resulted in a 16 day delay of tumor regrowth, which was markedly longer than the delay (ca 6 days) obtained after PDT under identical conditions without the preirradia-tion. Thus, pretreatment of pigmented tumors with HPP 1064 nm light appears to enhance their susceptibility to conventional PDT. The tumor response was further enhanced by repeating the combined HPP/PDT treatment at an interval of 10 days (regrowth delay: 27 days), as well as by applying hyperthermia immediately after HPP/PDT (regrowth delay: ca 34 days).