In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system.
An in vivo fluorescence monitoring and photodynamic therapy (PDT) study was performed using the new photosensitizer lutetium texaphyrin (Lu-Tex). This photosensitizer is water soluble and has the additional advantage of strong absorption near 730 nm. C26 colon carcinoma was transplanted in the foot of BALB/c mice. In vivo fluorescence spectroscopy was applied to study Lu-Tex tissue distribution kinetics. For this purpose, fluorescence intensity both in the foot with the tumor and in the normal foot was measured in vivo by the laser-induced fluorescence (LIF) system. For PDT, both feet of the mice were irradiated simultaneously with the use of a new high intensity pulsed light delivery system, the Photodyne. The results of the LIF measurements showed that the maximal fluorescence intensity ratio between the normal and tumor bearing foot (FIR) was observed 24-48 h after the agent injection. Photoirradiation with doses from 90 to 240 J cm-2 (0.6 J cm-2 per 2 ms pulse, 1 Hz) 24 h after injection of Lu-Tex at a dose of 10 mg kg-1 caused significant tumor necrosis and delay in the tumor growth rate. The antitumor effect was enhanced with increasing light doses. Normal tissue response to PDT with Lu-Tex was determined as the damage index of the normal foot, which was irradiated simultaneously with the tumor bearing foot. The normal tissue response after PDT with Lu-Tex was compared with 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PP), chlorin e6 (Chl) and Photofrin (PII) at the same values of antitumor effect. The results showed that at 50, 80 and 100% inhibition of tumor growth the orders of the values of normal foot damage indexes were as follows: ALA > Lu-Tex > or = PII > Chl, PII > ALA > Lu-Tex > Chl and PII > Lu-Tex > ALA > Chl respectively.
Kostenich
G
G
Plastic Surgery Department, Sheba Medical Center, Tel Hashomer, Israel.
Orenstein
A
A
Roitman
L
L
Malik
Z
Z
Ehrenberg
B
B
D000818:Animals; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D005260:Female; D005528:Foot / Q000473:pathology; D007834:Lasers; D008187:Lutetium; D008665:Metalloporphyrins / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use; D012995:Solubility; D013050:Spectrometry, Fluorescence; D014867:Water
D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; C102825:motexafin lutetium; C006969:chlorin; D008187:Lutetium; C437683:motexafin gadolinium; D017323:Dihematoporphyrin Ether