Tissue uptake, distribution, and potency of the photoactivatable dye chloroaluminum sulfonated phthalocyanine in mice bearing transplantable tumors.
The potency of chloroaluminum sulfonated phthalocyanine (ClAlSPc) as a photosensitizing agent for photodynamic therapy of cancer was evaluated in vivo by its ability to be taken up and retained by murine tumors of diverse histological origin. Antitumor effects following laser irradiation were evaluated by measurement of the tumor weights of dissected-out tumor masses. Three tumors (Colo 26, a colorectal carcinoma; M5076, a reticulum cell sarcoma; and UV-2237, a fibrosarcoma) growing s.c. in the flank region retained substantially greater quantities of ClAlSPc than did adjacent skin and muscle achieving peak values 24-48 h after the i.v. administration of ClAlSPc (10 mg/kg). The relative magnitude of ClAlSPc retention by these tumors was Colo 26 greater than M5076 greater than UV-2237. However, normal liver and spleen were organs which retained the greatest amounts of ClAlSPc even compared to the s.c. grown tumors and other normal tissues examined. Flow cytometric analysis of tumor cell suspensions obtained from collagenase-digested tumors showed that individual neoplastic cells were capable of taking up and retaining ClAlSPc. Photodynamic therapy, undertaken by i.v. administration of dye (5 mg/kg) followed 24 h later by local laser light irradiation (675 nm, 100 J), brought about significant (Colo 26, M5076, and 3LL tumors) and obvious but nonsignificant (UV-2237 tumor) reductions in tumor weights, as assessed 5 days later. Thus, selective tumor retention of ClAlSPc coupled with a significant response to red light produced dramatic alterations in cancer growth.
Chan
W S
WS
Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.
Marshall
J F
JF
Lam
G Y
GY
Hart
I R
IR
D000535:Aluminum / Q000493:pharmacokinetics*; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007700:Kinetics; D053685:Laser Therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; D000535:Aluminum