Photodynamic therapy with Pd-bacteriopheophorbide (TOOKAD):: Successful in vivo treatment of human prostatic small cell carcinoma xenografts

被引:164
作者
Koudinova, NV
Pinthus, JH
Brandis, A
Brenner, O
Bendel, P
Ramon, J
Eshhar, Z
Scherz, A
Salomon, Y [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
[3] Weizmann Inst Sci, Dept Plant Sci, IL-76100 Rehovot, Israel
[4] Weizmann Inst Sci, Expt Anim Ctr, IL-76100 Rehovot, Israel
[5] Weizmann Inst Sci, Dept Chem Serv, IL-76100 Rehovot, Israel
[6] Chaim Sheba Med Ctr, Dept Urol, IL-52621 Tel Hashomer, Israel
关键词
photodynamic therapy; small cells carcinoma of prostate; bone metastasis; palladium-Bacteriopheophorbide; xenogroft;
D O I
10.1002/ijc.11002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive nonepithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (is an element of(0) similar to 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CDI-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:782 / 789
页数:8
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