Pharmacokinetic analysis of octa-alpha-butyloxy-zinc phthalocyanine in mice bearing Lewis lung carcinoma.
OBJECTIVE
In this study, the pharmacokinetics of octa-alpha-butyloxy-zinc phthalocyanine (8-alpha-bo-ZnPc) was studied with regard to Lewis lung carcinoma in mice after intravenous administration of 7.8 mumole/kg body weight at different incubation intervals.


BACKGROUND
The newly synthesized potential photosensitizer 8-alpha-bo-ZnPc is characterized by a high absorption coefficient at the far red wavelength (735 nm) with a good singlet oxygen quantum yield.


METHODS
After intravenous administration of 7.8 mumole/kg body weight in mice bearing Lewis lung carcinoma, the accumulated photosensitizer was chemically extracted (at incubation intervals of 2, 6, 12, 24, 48, and 168 hours) from selected tissues, and the concentrations were measured by absorption spectroscopy.


RESULTS
The parenchymatous organs, liver, and spleen showed maximum 8-alpha-bo-ZnPc concentrations after 6 hours of incubation. An extensive uptake was detected in lung extracts taken at 6, 12, 24, and 48 hours. The malignant tissue did not accumulate high 8-alpha-bo-ZnPc during the entire investigation period. The photosensitizer extracted from muscle, representing normal tumor-surrounding tissue and skin, was even lower.


CONCLUSIONS
Because of the extremely low accumulation rate of the tumor, 8-alpha-bo-ZnPc is suggested to be administered topically or in combination with a suitable carrier system in order to increase the photosensitizer concentration in the target tissue, as well as to decrease the loss of dye to other tissues.
Ismail
M S
MS
Department of Laser Medicine, Neukölln Hospital, Berlin, Germany.
Dressler
C
C
Koeppe
P
P
Senz
R G
RG
Röder
B
B
Weitzel
H
H
Berlien
H P
HP
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism*; D007211:Indoles / Q000493:pharmacokinetics*; D054833:Isoindoles; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000627:therapeutic use*; D026082:Singlet Oxygen; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D017967:Zinc Compounds
D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; D010100:Oxygen