Variation in the distribution of a phthalocyanine photosensitizer in naturally occurring tumors of animals.

Jcmllldd J J AND PIIOII:il]I:IIK~ Journal of P h o t o c h e m i s t r y and Photobiology n , ~ B: Biology 27 (1995) 271-277 ELSEVIER News and Views Variation in the distribution of a phthalocyanine photosensitizer in naturally occurring tumors of animals George M. Peary, Tatiana B. Krasieva, Bruce J. Tromberg, E. Dave Eusantos, Michael W. Berns Beckman Laser Institute and Medical Clinic, College of Medicine, University of California, Irvine, CA 92715, USA 1. Introduction The biodistribution and cytotoxicity of photosensi- tizers have been shown to vary in tumors, not only between classes of photosensitizer [1-5], but also be- tween differently sulfonated forms of the same parent compound [6-14]. For example, the distribution has been reported to be different for related phthalocyanine compounds when viewed in the same tumor model [14,15]. In addition, the local hypoxia which results from early vascular collapse induced by photodynamic therapy (PDT) has been observed to protect tumor cells from the direct effects of photodynamic cytotoxicity in vivo by limiting the oxygen availability for singlet oxygen generation [16], further suggesting that the distribution of a photosensitizer within a tumor can influence its efficiency for that tumor type. It has been proposed that a variety of tissue factors may be responsible for the preferential uptake and/or retention of hematoporphyrin derivative [17]. It is con- ceivable that these factors could vary substantially be- tween tumor types. When different tumors were im- planted on the chick chorioallantoic membrane (CAM) model, photosensitizer uptake varied with tumor type [18]. Thus the uptake and distribution of a photosen- sitizer are clearly complex functions which may be influenced by both the chemical properties of the pho- tosensitizer and the physiologic behavior of a specific tumor which may vary between tumor types. In this report, we evaluate the intratumor distribution of a phthalocyanine preparation in three different, naturally occurring, domestic dog and cat tumors. Our goal was to determine whether the same intratumor biodistribution could be observed in a variety of naturally occurring tumors. Lack of uniformity would highlight 1011-1344/95/$09.50 © 1995 Elsevier Science S.A. All rights reserved SSDI 1011-1344(94)07075-X problems in making generalizations or applying infor- mation about tumor biodistribution, mechanisms of action or efficiency of a specific photosensitizer based on a limited tumor model. We conclude that it is important to study the photosensitizer biodistribution and efficiency in naturally occurring tumor lines in order to determine whether differences exist between tumor types, and if such can be correlated to clinical response. 2. Experimental details A chloroaluminum sulfonated phthalocyanine (AISPc) preparation was used in clinical studies of the response of spontaneously occurring, natural tumors of domestic dogs and cats to PDT. The product was obtained in solution at a concentration of 300 mg ml- 1 (Ciba-Geigy Dyestuffs and Chemicals, Basel, Switzer- land), lyophilized to a powder, resuspended in Dul- becco's phosphate-buffered saline ( 1 × ) (GIBCO, Grand Island, NY) to a concentration of 1 mg ml-1, placed in 6 ml or 10 ml amber vials and stored frozen at - 2 0 °C, in the dark, until needed for patient treatment. High pressure liquid chromatography was used to identify and quantify the phthalocyanine content of the prepared solution, revealing that it is composed primarily of trisulfonated ($3) and tetrasulfonated ($4) compounds, with some disulfonated ($2) compound and a highly sulfonated A1Pc compound possibly containing a sulfonate as an axial ligand on the central metal ion. Veterinary patients received an intravenous injection of the AISPc preparation at a dosage of 1 mg kg-1 of body weight. After 48 h, samples of tumor tissue were obtained, placed in embedding medium for frozen tissue specimens (OCT Compound, Tissue-Tek-Miles, Elk-