Objective: In in vitro photodynamic therapy, the LD50 of Pc 181 has been reported to be 7 to 8 times less than that of silicon phthalocyanine 4 (Pc 4). The Optical Pharmacokinetic System (OPS) can measure photosensitizer concentrations in accessible tissues non-invasively. We used OPS to evaluate the tumor pharmacokinetics of Pc 181 and Pc 4 and the tissue drug distribution in SCID mice bearing either human breast cancer MDA-MB-231 or human head and neck squamous cell carcinoma SCC-15 xenografts.
Methods: Following iv administration of 2.5 mg/kg Pc 181 or 2 mg/kg Pc 4 to SCID mice, OPS measurements were taken on tumor and normal tissues between 5 and 4320 min in vivo or in situ.
Results: Large variations in tumor Pc 181 concentrations were observed among mice. In MDA-MB-231 tumors, the Pc 181 concentration peaked at 240 min, and was retained in the tumor. Tumor Pc 181 concentrations were much less than the tumor Pc 4 concentrations at an equimolar dose. Pc 181 concentrations were the highest in liver, followed by spleen, and kidney. In mice bearing SCC-15 xenografts, skin and underlying tissue Pc 181 concentrations were higher than
tumor concentrations at all time points examined.
Conclusions: This first Pc 181 pharmacokinetics study described a tissue Pc 181 distribution similar to that of Pc 4. However, tumor Pc 181 concentrations were lower than those of Pc 4 at equimolar doses.
Objective: Pc 4, a phthalocyanine photosensitizer in Phase I photodynamic therapy (PDT) trials, requires laser activation near 672 nm. For effective PDT, photosensitizer must be present in the target tissues. OPS uses elastic scattering spectroscopy to measure Pc 4 optical absorption non-invasively, and that absorbance can be converted to concentration using Pc 4 standard curves in 1% Intralipid®. In this study, we used OPS to evaluate Pc 4 optical absorption with time in subcutaneous tumor (with or without laser activation) and in contralateral skin. Tumor response was also evaluated after Pc 4-PDT.
Conclusions: Both Pc 4 and hemoglobin optical absorption could be monitored by OPS. The decrease of Pc 4 absorption after PDT and the appearance of d-hbg indicated that alterations occurred in the tumor following Pc 4-PDT. The increase in d-hbg suggests that oxygen was not replaced completely, possibly due to circulation damage in tumor.
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