chloroaluminum-tetrasulfophthalocyanine and Glioma

Laser-induced fluorescence has been used to measure tissue levels of chloroaluminum sulfonated phthalocyanine in vivo in an implanted hamster cheek pouch carcinoma tumor model. The drug was excited at 610 nm via a pulsed nitrogen laser-pumped dye laser, and fluorescence intensity was monitored at 684 nm for up to 30 days after drug administration. Data were acquired noninvasively with high temporal and spatial resolution using the laser-induced fluorescence apparatus and were analyzed with a multicompartment pharmacokinetic model. In addition, our published data on a C6-BAG glioma rat brain tumor model were analyzed to illustrate the effect of different tumor models on the rates. The rates extracted from the pharmacokinetic model elucidate the mechanisms of drug uptake and retention in the cheek pouch and brain tumor models. The laser-induced fluorescence approach should lead to better drug dosimetry for photochemotherapy and allow quick characterization of the pharmacokinetics of new photosensitizers in tissue.

Topics: Animals; Brain Neoplasms; Cheek; Cricetinae; Fluorescence; Glioma; Indoles; Lasers; Male; Mesocricetus; Models, Biological; Mouth Neoplasms; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Rats

The ability of laser-induced fluorescence spectroscopy to delineate tumor margins intraoperatively was studied using a rat intracerebral glioma model. A fluorescent dye, chloro-aluminum phthalocyanine tetrasulfonate (ClAlPcS4), was injected intravenously 24 hours before tumor resection. The animals underwent tumor resection under the operating microscope, guided by laser-induced fluorescence measurement in one group (Group 1) and visual assessment in the other (Group 2). The Group 1 rats had a significantly reduced volume of residual tumor following resection (0.5 +/- 0.2 cu mm vs. 13.7 +/- 4.0 cu mm, mean +/- standard error of the mean, p less than 0.02). Three of the nine animals in Group 1 were tumor-free at 2 weeks following resection, compared with none of the 10 rats in Group 2 (p less than 0.05). Interference from brain autofluorescence was minimized using spectrally resolved detection and the ClAlPcS4 dye, which has a 680-nm fluorescence peak significantly higher than the 470-nm autofluorescence peak of normal brain. Contrast ratios of up to 40:1 were found for glioma:normal brain fluorescence signals. Spatially-resolved spectra were acquired in approximately 5 seconds using a fiberoptic probe. This study demonstrates the ability of an intraoperative laser-induced fluorescence system to detect tumor margins that could not be identified with the operating microscope.

Topics: Animals; Brain Neoplasms; Fluorescent Dyes; Glioma; Indoles; Lasers; Male; Organometallic Compounds; Rats; Rats, Inbred F344; Spectrometry, Fluorescence