title: Uptake and retention of the photosensitizer mono-L-asparthyl chlorine e6 in experimental malignant glioma.
abstract: The objective of the study was to investigate the potential of mono-L-aspartyl chlorine e6 (NPe6), a water-soluble photosensitizer derived from chlorophyll, for use in photodynamic diagnosis (PDD) of malignant brain tumor. A C6 glioma cell line was transplanted in the SD rat brain to create a brain tumor model. Five days after transplantation, NPe6 was administrated via the tail vein at concentrations ranging from 1.25 to 10 mg/kg; then the skull was opened in the rat brain, the site of tumor transplant was irradiated with a diode laser beam at 664 nm, and the time-course intensity and distribution of emerging fluorescence were observed. Furthermore, the correlation between fluorescence distribution and histopathological findings was investigated in the removed brain. Fluorescence was observed in the site of brain tumor transplant from 5 min after injection, and stable fluorescence was recognized at the site until 4 h after administration. No differences were noted in fluorescence intensity at NPe6 doses of 2.5 mg/kg or more; therefore, it was possible to estimate the optimal dose range. Fluorescence distribution had a clear correlation with tumor cell density, and it was possible to capture the margin of tumor cell invasion with fluorescence. The photosensitizer NPe6 is capable of assessing tumor cell density in malignant glioma tissue in terms of differences in fluorescence intensity. The usefulness of PDD using 5-aminoleveulinic acid during surgery for malignant glioma has been recognized in recent years. The results of the present study suggested the potential of NPe6 as a promising photosensitizer for use in PDD for accurate grasp of the extent of removal during the course of malignant glioma surgery.
authors: Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku, Tokyo 160-0023, Japan.
authors: Hiroyuki
authors: H
authors: Matsumura
authors: Jiro
authors: J
authors: Akimoto
authors: Jo
authors: J
authors: Haraoka
authors: Katsuo
authors: K
authors: Aizawa
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis*; D045744:Cell Line, Tumor; D005910:Glioma / Q000175:diagnosis*; D007834:Lasers; D008297:Male; D009368:Neoplasm Transplantation; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin
references: Photochem Photobiol. 1987 Jun;45(6):879-89
references: 2957705
references: Lasers Surg Med. 2000;26(1):83-9
references: 10637007
references: J Clin Laser Med Surg. 1996 Oct;14(5):263-70
references: 9612192
references: Photochem Photobiol. 1995 Jun;61(6):646-9
references: 7568411
references: Lasers Surg Med. 1989;9(2):90-101
references: 2523995
references: Cancer Res. 1978 Aug;38(8):2628-35
references: 667856
references: Gan To Kagaku Ryoho. 2000 Oct;27(12):1876-8
references: 11086434
references: Cancer Res. 1990 Jul 1;50(13):3985-90
references: 2354446
references: Lancet Oncol. 2006 May;7(5):392-401
references: 16648043
references: Photochem Photobiol. 1987 Nov;46(5):789-93
references: 3441501
references: Photochem Photobiol. 1992 Jul;56(1):51-6
references: 1508982
references: Neurosurgery. 1990 Feb;26(2):248-54
references: 2137904
references: Hepatology. 1989 Dec;10 (6):995-7
references: 2583692
references: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1785-9
references: 1542672
references: J Photochem Photobiol B. 1997 May;39(1):81-3
references: 9210325
references: Photochem Photobiol. 1989 Aug;50(2):221-8
references: 2528753
references: Neurosurgery. 1998 May;42(5):1044-55; discussion 1055-6
references: 9588549
references: Cancer Res. 1992 May 15;52(10):2890-3
references: 1581904
references: Neurosurgery. 1985 Dec;17(6):883-90
references: 2934641
references: Semin Surg Oncol. 1995 Sep-Oct;11(5):335-45
references: 7569555
references: Lasers Surg Med. 1989;9(2):102-8
references: 2523992
references: Cancer Res. 1987 Sep 1;47(17):4681-5
references: 2957047
references: J Neurosurg. 1988 Jul;69(1):1-14
references: 3288722
references: J Neurosurg. 1948 Jul;5(4):392-8
references: 18872412
references: Cancer. 1998 Jan 15;82(2):421-7
references: 9445202
references: J Natl Cancer Inst. 1988 May 4;80(5):330-6
references: 2965763
references: Cancer Res. 1994 Sep 1;54(17):4564-8
references: 8062241
references: J Natl Cancer Inst. 1988 Dec 21;80(20):1599-605
references: 2973528
references: Neurosurgery. 1988 Nov;23(5):557-63
references: 2849067
references: J Photochem Photobiol B. 1992 Jul 30;14 (4):275-92
references: 1403373
references: Photochem Photobiol. 1996 Oct;64(4):671-5
references: 8863472
references: J Neurosurg. 2000 Dec;93(6):1003-13
references: 11117842
references: J Neurosurg Sci. 1980 Jul-Dec;24(3-4):119-29
references: 6267229
references: J Neurosurg. 2001 Aug;95(2):190-8
references: 11780887