Preoperative Prediction of Whether Intraoperative Fluorescence of Protoporphyrin IX Can Be Achieved by 5-Aminolevulinic Acid Administration

Satoshi Utsuki, Hidehiro Oka, Chihiro Kijima, Madoka Inukai, Kiyotaka Fujii, Masahiro Ishizuka, Kiwamu Takahashi, Katsushi Inoue

Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Japan.
SBI ALApromo Co., Ltd., Tokyo, Japan.

DOI: 10.4236/ijcm.2012.32026                

Abstract

Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection, using 5-aminolevulinic acid (5-ALA), is among the most valuable tools for determining tumor removal area. However, PPIX fluorescence is not necessarily achieved during an operation visually even when 5-ALA is used, and we do not know until tumor exposure to the excitation light of the ultraviolet region whether PPIX fluorescence has been achieved. When a particular biopsy and frozen section diagnosis is made, the reason for lack of PPIX fluorescence in the tissue cannot be judged. We do not know whether the tumor fails to fluoresce or no fluorescence is seen because it is not the main body of the tumor. We investigated whether the presence or absence of tumor fluorescence could be predicted by examining urinary porphyrin before surgery, at the time of intraoperative fluorescence diagnosis using 5-ALA. The urine of brain tumor patients 2 hours after 5-ALA administration was irradiated with a 405 ± 1 nm laser light. The patients were divided into a fluorescent urine group and negative fluorescent urine group. Red fluorescence was observed in response to the 405 ± 1 nm laser beam for all tumors in the fluorescent urine group. Clear red fluorescence was not observed even with 405 ± 1 nm laser beam irradiation in any tumors in the negative fluorescent urine group. Preoperative prediction of the intraoperative fluorescence of PPIX can be achieved by observation of urine 2 hours after 5-ALA administration with exposure to a 405 ± 1 nm laser light.

Keywords

5-Aminolevulinic Acid; Intraoperative Fluorescence; Coproporphyrin; Protoporphyrin IX; Urinary Porphyrin

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. K. Bisland, E. A. Goebel, N. S. Hassanali, C. Johnson and B. C. Wilson, “Increased Expression of Mitochondrial Benzodiazepine Receptors Following Low-Level Light Treatment Facilitates Enhanced Protoporphyrin IX Production in Glioma-Derived Cells in Vitro,” Lasers in Surgery and Medicine, Vol. 39, No. 8, 2007, pp. 678-684. doi:10.1002/lsm.20544
[2]	W. Stummer, A. Novotny, H. Stepp, C. Goetz, K. Bise and H. J. Reulen, “Fluorescence-Guided Resection of Glioblastoma Multiforme by Using 5-Aminolevulinic Acid-Induced Porphyrins: A Prospective Study in 52 Consecutive Patients,” Journal of Neurosurgery, Vol. 93, No. 6, 2000, pp. 1003-1013. doi:10.3171/jns.2000.93.6.1003
[3]	S. Utsuki, H. Oka and K. Fujii, “Intraoperative Photodynamic Diagnosis of Brain Tumors Using 5-Aminolevu-linic Acid,” In: A. L. Abujamra, Ed., Diagnostic Tech-niques and Surgical Management of Brain Tumors, In-Tech, Rijeka, 2011, pp. 227-244.
[4]	S. Utsuki, H. Oka, S. Sato, S. Suzuki, S. Shimizu, S. Tanaka and K. Fujii, “Possibility of Using Laser Spectroscopy for the Intraoperative Detection of Nonfluorescing Brain Tumors and the Boundaries of Brain Tumor Infiltrates,” Journal of Neurosurgery, Vol. 104, No. 4, 2006, pp. 618-620. doi:10.3171/jns.2006.104.4.618
[5]	S. Utsuki, H. Oka, K. Fujii, N. Miyoshi, M. Ishizuka, K Takahashi and K. Inoue, “Differential Metabolism of 5-ALA in Patients with Brain Tumors,” In: N. Miyoshi and R. H. Pottier, Ed., In Hope of Going over the Present Clinical PD and PDT, Sankeisha, Nagoya, 2011, pp. 160-173.
[6]	Q. Peng, K. Berg, J. Moan, M. Kongshaug and J. M. Nesland, “5-Aminolevulinic Acid-Based Photodynamic Therapy: Principles and Experimental Research,” Photochemistry and Photobiology, Vol. 65, No. 2, 1997, pp. 235-251. doi:10.1111/j.1751-1097.1997.tb08549.x
[7]	S. Utsuki, H. Oka, S. Sato, S. Suzuki, S. Shimizu, Y. Tanizaki, K. Kondo, Y. Miyajima and K. Fujii, “Histological Examination of False Positive Tissue Resection Using 5-Aminolevulinic Acid-Induced Fluorescence Guidance,” Neurologia Medico-Chirurgica (Tokyo), Vol. 47, No. 5, 2007, pp. 210-214. doi:10.2176/nmc.47.210
[8]	S. Utsuki, N. Miyoshi, H. Oka, Y. Miyajima, S. Shimizu, S. Suzuki and K. Fujii, “Fluorescence-Guided Resection of Metastatic Brain Tumors Using 5-Aminolevulinic Acid-Induced Porphyrins—Pathological Study,” Brain Tumor Pathology, Vol. 24, No. 2, 2007, pp. 53-55. doi:10.1007/s10014-007-0223-3
[9]	T. Ishikawa and H. Nakagawa, “Human ABC Transporter ABCG2 in Cancer Chemotherapy and Pharmacogenomics,” Journal of Experimental Therapeutics and Oncology, Vol. 8, No. 1, 2009, pp. 5-24.
[10]	A. Tamura, Y. Onishi, R. An, S. Koshiba, K. Wakabayashi, K. Hoshijima, W. Priebe, T. Yoshida, S. Kometani, T. Matsubara, K. Mikuriya and T. Ishikawa, “In Vitro Evaluation of Photosensitivity Risk Related to Genetic Polymorphisms of Human ABC Transporter ABCG2 and Inhibition by Drugs,” Drug Metabolism and Pharmacokinetics, Vol. 22, No. 6, 2007, pp. 428-440. doi:10.2133/dmpk.22.428
[11]	A. M. Bleau, J. T. Huse and E. C. Holland, “The ABCG2 Resistance Network of Glioblastoma,” Cell Cycle, Vol. 8, No. 18, 2009, pp. 2936-2944. doi:10.4161/cc.8.18.9504
[12]	Y. Jin, Z. Q. Bin, H. Qiang, C. Liang, C. Hua, D. Jun, W. A. Dong and L. Qing, “ABCG2 is Related with the Grade of Glioma and Resistance to Mitoxantone, a Chemotherapeutic Drug for Glioma,” Journal of Cancer Research and Clinical Oncology, Vol. 135, No. 10, 2009, pp. 1369-1376. doi:10.1007/s00432-009-0578-4