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. 2010 Jul;1(4):713-718.
doi: 10.3892/etm_00000110. Epub 2010 Jul 1.

Comparative photodynamic therapy study using two phthalocyanine derivatives

Edith Inés Yslas  1 , Laura Natalia Milla, Silvia Romanini, Edgardo Néstor Durantini, Mabel Bertuzzi, Viviana Alicia Rivarola
Affiliations

Comparative photodynamic therapy study using two phthalocyanine derivatives

Edith Inés Yslas et al. Exp Ther Med. 2010 Jul.

Abstract

In the present study, a comparative photodynamic therapy (PDT) study was performed using the phthalocyanine derivatives, ZnPc(OCH(3))(4) and ZnPc(CF(3))(4), in a mouse tumor model, under identical experimental procedures. We studied the ablation of tumors induced by PDT. The end-point was to compare the photodynamic efficacy of ZnPc(OCH(3))(4) and ZnPc(CF(3))(4). ZnPc(OCH(3))(4) and ZnPc(CF(3))(4) were administered intraperitoneally at a dose of 0.2 mg/kg body weight. The injections of drugs were carried out in Balb/c mice bearing subcutaneously inoculated LM2 mouse mammary adenocarcinoma. Histological examination and serum biochemical parameters were used to evaluate hepatic and renal toxicity and function. Phototherapeutic studies were achieved employing a light intensity of 210 J/cm(2). After PDT, tumoral regression analyses were carried out, and the degree of tumor cell death was measured utilizing the vital stain Evan's blue. In this pilot study, we revealed that the cytotoxic effect of ZnPc(OCH(3))(4) after PDT led to a higher success rate compared to ZnPc(CF(3))(4)-PDT when both were intraperitoneally injectioned. Both phthalocynanine derivatives were able to induce ablation in the tumors. In summary, these results demonstrate the feasibility of ZnPc(OCH(3))(4)- or ZnPc(CF(3))(4)-PDT and its potential as a treatment for small tumors.

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Figures

Figure 1.
Figure 1.
Serum concentration of creatinine in the control group, 1, 7 and 30 days after ZnPc(CF3)4 or ZnPc(OCH3)4 injection (0.2 mg/kg bw). Data represent the means ± SEM (n=5). *p<0.05.
Figure 2.
Figure 2.
Serum concentration of urea in the control group, 1, 7 and 30 days after ZnPc(CF3)4 or ZnPc(OCH3)4 injection (0.2 mg/kg bw). Data represent the means ± SEM (n=5). *p<0.05.
Figure 3.
Figure 3.
Serum concentration of GPT in the control group, 1, 7 and 30 days after ZnPc(CF3)4 or ZnPc(OCH3)4 injection (0.2 mg/kg bw). Data represent the means ± SEM (n=5). *p<0.05.
Figure 4.
Figure 4.
Microscopic image of a kidney from (A) a control mouse, (B) a mouse 10 days after treatment with ZnPc(OCH3)4 (0.2 mg/kg bw), and (C) a mouse 10 days after treatment with ZnPc(CF3)4 (0.2 mg/kg bw). Microscopic image of liver obtained from (D) a control mouse, (E) a mouse 10 days after treatment with ZnPc(OCH3)4 (0.2 mg/kg bw), and (F) a mouse 10 days after treatment with ZnPc(CF3)4 (0.2 mg/kg bw) (magnification x400). The specimens were stained with H&E.
Figure 5.
Figure 5.
(A) Effect of ZnPc(OCH3)4-PDT or ZnPc(CF3)4 on tumors. Tumors were either untreated or treated with ZnPc(OCH3)4 alone, light alone or ZnPc(OCH3)4-PDT, with light doses of 210 J/cm2. (B) Effect of ZnPc(CF3)4-PDT on tumors. Tumors were either untreated or treated with ZnPc(CF3)4 alone, light alone or ZnPc(CF3)4-PDT, with light doses of 210 J/cm2 (B). Data represent the means ± SEM of the volumes of 8 tumors in each experimental group.
Figure 5.
Figure 5.
(A) Effect of ZnPc(OCH3)4-PDT or ZnPc(CF3)4 on tumors. Tumors were either untreated or treated with ZnPc(OCH3)4 alone, light alone or ZnPc(OCH3)4-PDT, with light doses of 210 J/cm2. (B) Effect of ZnPc(CF3)4-PDT on tumors. Tumors were either untreated or treated with ZnPc(CF3)4 alone, light alone or ZnPc(CF3)4-PDT, with light doses of 210 J/cm2 (B). Data represent the means ± SEM of the volumes of 8 tumors in each experimental group.
Figure 6.
Figure 6.
Transverse tumor sections of mice injected with the vital stain Evan’s blue. A control ZnPc(OCH3)4-dark mouse (A), and mice treated with PDT and injected with Evan’s blue 1 day post-PDT (B), 4 days post-PDT (C), and 10 days post-PDT (D). A control ZnPc(CF3)4-dark mouse (E) and mice treated with PDT injected with Evan’s blue 1 day post-PDT (F), 4 days post-PDT (G), and 10 days post-PDT (H).
Figure 7.
Figure 7.
(A) H&E-stained tumor specimen obtained after 10 days from the untreated group (magnification x400). The organization of the tumor tissue is well-preserved and typical for this tumor type. (B) H&E-stained micrograph of a tumor 10 days after PDT with 0.2 mg/kg bw ZnPc(OCH3)4 by i.p. injection and light exposure of 210 J/cm2. The micrograph (x400) shows a large area of cell death and ruptured vasculature. (C) H&E-stained micrograph of a tumor 10 days after PDT using 0.2 mg/kg bw ZnPc(CF3)4 by i.p. injection and light exposure of 210 J/cm2. The micrograph (x400) shows a large area of cell death.
Figure 8.
Figure 8.
Tumor:skin ratio after injection of either ZnPc(OCH3)4 or ZnPc(CF3)4. Data represent the means ± SEM.
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