臨床泌尿器科64巻13号

2010年12月発行

綜説

5-アミノレブリン酸を用いた光線力学的診断・治療

著者： 小山政史¹ 朝倉博孝² 上野宗久¹

所属機関： ¹埼玉医科大学国際医療センター泌尿器腫瘍科 ²埼玉医科大学泌尿器科

ページ範囲：P.967 - P.977

文献概要

要旨　光線力学的診断（PDD）および治療（PDT）が着目されるようになり，100年以上の年月が過ぎた。光感受性物質としてはポルフィリン誘導体を主体に基礎ならびに臨床研究が進められてきたが，近年5-アミノレブリン酸（ALA）の登場で再びPDD，PDTへの関心が高まっている。本稿ではPDD，PDTの歴史から，現在行われているALAを用いた研究まで，泌尿器悪性腫瘍を中心に概説した。ALAは経口投与による腫瘍特異的PDD，PDTを可能にする元来天然に存在する物質である。今後ALAを用いたPDD，PDTが泌尿器悪性腫瘍に対してどのように応用されてゆくか，その可能性について諸氏の報告をまとめながら言及する。

参考文献

1）Raab O：Uber die Wirkung fluoreszierender Stoffe auf Infusorien. Z Biol 39：524-526, 1900

2）von Tappeiner H and Jodlbauer A：Uber die wirkung der photodynamischen（fluoreszierenden）stoffe auf protozoan und enzyme. Dtsch Arch Klin Med 80：427-487, 1904

3）Rall DP, Loo TL, Lane M, et al：Appearance and persistence of fluorescent material in tumor tissue after tetracycline administration. J Nat Cancer Inst 19：79-85, 1957

4）Whitmore WF Jr, Bush IM and Esquivel E：Tetracycline ultraviolet fluorescence in bladder carcinoma. Cancer 17：1528-1532, 1964

5）Policard A：Etude sur les aspects offerts par des tumeurs expérimentales examinées a la lumière de Wood. C R Soc Biol 91：1423-1428, 1924

6）Rassmussen-Taxdal DS, Ward GE and Figge FH：Fluorescence of human lymphatic and cancer tissues following high doses of intravenous hematoporphyrin. Cancer 8：78-81, 1955

7）Lipson RL and Baldes EJ：The photodynamic properties of a particular haematoporphyrin derivative. Arch Dermatol 82：508-516, 1960

8）Dougherty TJ, Kaufman JE, Goldfarb A, et al：Photoradiation therapy for the treatment of malignant tumors. Cancer Res 38：2628-2635, 1978

9）Windahl T, Andersson SO and Lofgren L：Photodynamic therapy of localised prostatic cancer. Lancet 336（8723）：1139, 1990

10）Uchibayashi T, Koshida K, Kunimi K, et al：Whole bladder wall photodynamic therapy for refractory carcinoma in situ of the bladder. Br J Cancer 71：625-628, 1995

11）Hisazumi H, Misaki T and Miyoshi N：Photoradiation therapy of bladder tumors. J Urol 130：685-687, 1983

12）Kato H, Furukawa K, Sato M, et al：Phase Ⅱ clinical study of photodynamic therapy using mono-L-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung. Lung Cancer 42：103-111, 2003

13）Yokota N, Yamamoto S, Terakawa S, et al：Selective accumulation and strong photodynamic effects of a new photosensitizer, ATX-S10.Na（Ⅱ）, in experimental malignant glioma. Int J Oncol 27：1207-1213, 2005

14）Kennedy JC, Pottier RH and Pross DC：Photodynamic therapy with endogenous protoporphyrin Ⅸ：basic principles and present clinical experience. J Photochem Photobiol B 6：143-148, 1990

15）Kriegmair M, Baumgartner R and Hofstetter AG：Intravesikale Instillation von Delta-Aminolävulinsäure（ALA）：eine neue Methode zur photodynamischen Diagnostik und Therapie. Laser Med 8：83, 1992

16）Grant WE, Hopper C, MacRobert AJ, et al：Photodynamic therapy of oral cancer：photosensitisation with systemic aminolaevulinic acid. Lancet 17：147-148, 1993

17）Peng Q, Warloe T, Berg K, et al：5-aminolevulinic acid-based photodynamic therapy：Clinical research and future challenges. Cancer 15：2282-2308, 1997

18）Taketani S, Adachi Y and Nakahashi Y：Regulation of the expression of human ferrochelatase by intracellular iron levels. Eur J Biochem 267：4685-4692, 2000

19）Doring F, Walter J, Will J, et al：Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest 101：2761-2767, 1998

20）Xiang J, Hu Y, Smith DE, et al：PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res 1122：18-23, 2006

21）Rud E, Gederaas O, Høgset A, et al：5-aminolevulinic acid, but not 5-aminolevulinic acid esters, is transported into adenocarcinoma cells by system BETA transporters. Photochem Photobiol 71：640-647, 2000

22）Krieg RC, Messmamn H, Rauch J, et al：Metabolic characterization of tumor cell-specific protoporphyrin Ⅸ accumulation after exposure to 5-aminolevulinic acid in human colonic cells. Photochem Photobiol 76：518-525, 2002

23）竹原良記，村中式部：5-アミノレブリン酸―光線力学的治療の有効性に注目して．岡山学院大学・岡山短期大学紀要 30：45-61，2007

24）Schoenfeld N, Epstein O, Lahav M, et al：The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders. Cancer Lett 43：43-48, 1988

25）Krieg RC, Fickweiler S, Wolfbeis OS, et al：Cell-type specific protoporphyrin Ⅸ metabolism in human bladder cancer in vitro. Photochem Photobiol 72：226-233, 2000

26）大崎能伸，澁川紀代子：［気管支鏡的画像診断の最前線］Photodynamic Diagnosisの診断への応用．気管支学 28：482-486，2006

27）Henderson BW and Bellnier DA：Tissue localization of photosensitizers and the mechanism of photodynamic tissue destruction. Ciba Found Symp 146：112-125, 1989

28）Vander Heiden MG, Cantley LC and Thompson CB：Understanding the Warburg effect：the metabolic requirements of cell proliferation. Science 22：1029-1033, 2009

29）Inoue K, Karashima T, Kamada M, et al：Regulation of 5-aminolevulinic acid-mediated protoporphyrin Ⅸ accumulation in human urothelial carcinomas. Pathobiology 76：303-314, 2009

30）金子貞男：脳腫瘍に対する光モニタリング―ALA induced Pp Ⅸによる術中脳腫瘍蛍光診断．Neurol Surg 29：1019-1031，2001

tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy. Cancer Res 63：7986-7994, 2003

32）Popken G, Wetterauer U, Schultze-Seemann W：Kidneypreservingtumor resection in renal cell carcinoma with photodynamic detection by 5-aminolaevulinic acid：Preclinicaland preliminary clinical results. BJU Int 83：578, 1999

33）Hoda MR and Popken G：Surgical outcomes of fluorescence-guided laparoscopic partial nephrectomy using 5-aminolevulinic acid-induced protoporphyrin Ⅸ. J Surg Res 154：220-225, 2009

34）Sultan SM, El-Doray AA, Hofstetter A, et al：Photodynamic selectivity of 5-aminolevulinic acid to prostate cancer cells. J Egypt Natl Canc Inst 18：382-386, 2006

35）Kupelian P, Katcher J, Levin H, et al：External beam radiotherapy versus radical prostatectomy for clinical stage T1-2 prostate cancer：therapeutic implications of stratification by pretreatment PSA levels and biopsy Gleason scores. Cancer J Sci Am 3：78-87, 1997

36）Zaak D, Sroka R, Khoder W, et al：Photodynamic diagnosis of prostate cancer using 5-aminolevulinic acid：first clinical experiences. Urology 72：345-348, 2008

37）Adam C, Salomon G, Walther S, et al：Photodynamic diagnosis using 5-aminolevulinic acid for the detection of positive surgical margins during radical prostatectomy in patients with carcinoma of the prostate：a multicentre, prospective, phase 2 trial of a diagnostic procedure. Eur Urol 55：1281-1288, 2009

38）Babjuk M, Oosterlinck W, Sylvester R, et al：EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder：European Association of Urology（EAU）. Eur Urol 54：303-314, 2008

39）Brausi M, Collette L, Kurth K, et al；EORTC Genito-Urinary Tract Cancer Collaborative Group：Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder：a combined analysis of seven EORTC studies. Eur Urol 41：523-531, 2002

40）Sylvester RJ, van der Meijden AP, Oosterlinck W, et al：Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables：a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49：466-475, 2006

41）Jocham D, Stepp H and Waidelich R：Photodynamic diagnosis in urology：state-of-the-art. Eur Urol 53：1138-1148, 2008

42）Klan R Loy V and Huland H：Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol 146：316-318, 1991

43）Schwaibold HE, Sivalingam S, May F, et al：The value of a second transurethral resection for T1 bladder cancer. BJU Int 97：1199-1201, 2006

44）Brauers A, Buettner R and Jakse G：Second resection and prognosis of primary high risk superficial bladder cancer：is cystectomy often too early? J Urol 165：808-810, 2001

45）Hungerhuber E, Stepp H, Kriegmair M, et al：Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology 69：260-264, 2007

46）Daniltchenko DI, Riedl CR, Sachs MD, et al：Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer：5-year results of a prospective randomized study. J Urol 174：2129-2133, 2005

47）Denzinger S, Burger M, Walter B, et al：Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis：8-year results of prospective randomized study. Urology 69：675-679, 2007

48）Webber J, Kessel D and Fromm D：Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 68：31-37, 1997

49）Kaneko S：A current overview：photodynamic diagnosis and photodynamic therapy using 5-aminolevulinic acid in neurosurgery. JJSLSM 29：135-146, 2008

50）Kausch I, Sommerauer M, Montorsi F, et al：Photodynamic diagnosis in non-muscle-invasive bladder cancer：a systematic review and cumulative analysis of prospective studies. Eur Urol［Epub ahead of print］

51）Burger M, Stief CG, Zaak D, et al：Hexaminolevulinate is equal to 5-aminolevulinic acid concerning residual tumor and recurrence rate following photodynamic diagnostic assisted transurethral resection of bladder tumors. Urology 74：1282-1286, 2009

52）井上啓史，久野貴平，福原秀雄，他：光力学診断補助下経尿道的膀胱腫瘍切除術の臨床経験．日泌尿会誌 100：661-670，2009

experiment. Oncology 76：118-125, 2009