Bis(di-isobutyl octadecylsiloxy)
silicon 2,3-naphthalocyanine (
isoBOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for
photodynamic therapy (
PDT). Tissue distributions were studied in
tumor-bearing rats as a function of delivery system and time following administration. The
tumor model was an N-(4-[5-nitro-2-furyl]-2-thiazolyl)
formamide (
FANFT)-induced urothelial cell
carcinoma transplanted into one hind leg of male Fischer 344 rats;
isoBOSINC was delivered to the rats by
intravenous injection of 0.50 mg/kg of
body weight as a
suspension either in 10%
Tween 80 in saline (
Tween) or 10% (
Cremophor EL +
propylene glycol) in saline (
Cremophor). The
isoBOSINC was isolated from several tissues and organs, as well as
tumors and peritumoral muscles and skin. Quantitation was by a high-performance liquid chromatographic technique with detection that utilizes the native fluorescence of the naphthalocyanine derivative. Independent of the delivery system, the
dye was retained in
tumors at higher concentrations than in normal tissues, except for spleen and liver. The
isoBOSINC retention in
tumors was high and was vehicle dependent. For
Tween, the maximal ratio of
dye in
tumor versus peritumoral muscle occurred 12 h after injection; for
Cremophor, the maximal ratio occurred later, 336 h postinjection. When the
drug was delivered in
Tween,
isoBOSINC in serum showed two compartment kinetics: half-lives of about 2 and 11 h were found for the distribution and the elimination phases, respectively. When
Cremophor was the vehicle, the elimination half-life was about 20 h, and one compartment kinetics was observed. The latter findings may explain the generally higher levels of the
dye attained by the tissues at later times with
Cremophor as the vehicle. An interesting exception was that after 7 and 14 days postinjection in
Tween, the levels of
dye found in testes were six- to seven-fold higher than those found after
Cremophor delivery. Levels of
dye were very low or not detectable in the brain. Optimal parameters for
PDT of
tumors with this novel
photosensitizer are clearly time- and vehicle-dependent, and future
PDT studies will need to incorporate these modulators.