Abstract：
:Benzoporphyrin derivative, monoacid ring A (BPD-MA), currently in clinical trials as a photosensitizer for photodynamic therapy for cancer, consists of two regioisomers (A1 and A2) present in equal proportions. The contribution of the regioisomers to the overall photosensitizing potency of BPD-MA was tested in vitro and in vivo. The in vitro photosensitizing potencies of BPD-MA-A1 and -A2 were tested in a standard cytotoxicity assay using M1 (rhabdomyosarcoma of DBA/2 mice) tumor cells and were found to be equivalent. The in vivo photosensitizing efficacies of the regioisomers were tested in the M1 tumor model in DBA/2 mice and were also found to be equivalent. Biodistribution of the regioisomers in mouse plasma, tumor and liver was studied in M1 tumor-bearing DBA/2 mice at 15 min and 3 hr post intravenous injection of [14C]BPD-MA-A1/A2 at 4 mg/kg body weight. Plasma and extracts from tumor and liver were analysed by HPLC and tested for radioactivity. The two regioisomers were eliminated from plasma and liver at different rates, which resulted in A1:A2 ratios of 1:0.28 in plasma and 1:0.75 in liver at 3 hr post injection. The differential elimination was not observed to any significant degree in the tumor, where even at 3 hr post injection the A1:A2 ratio was 1:1.15. Therefore, we concluded that in tumor tissue, at 3 hr post injection, the time at which laser photodynamic therapy is carried out, both regioisomers were present in about equal proportions. Further, both regioisomers were fully active as determined by an in vitro cytotoxicity assay following extraction.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Richter AM,Jain AK,Canaan AJ,Waterfield E,Sternberg ED,Levy JGdoi
10.1016/0006-2952(92)90313-8subject
Has Abstractpub_date
1992-06-09 00:00:00pages
2349-58issue
11eissn
0006-2952issn
1873-2968pii
0006-2952(92)90313-8journal_volume
43pub_type
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journal_title：Biochemical pharmacology
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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doi：10.1016/j.bcp.2011.11.001
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更新日期：1992-07-22 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1984-12-15 00:00:00
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更新日期：2004-06-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90105-8
更新日期：1982-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2009-09-15 00:00:00
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pub_type： 杂志文章
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更新日期：2003-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90622-2
更新日期：1986-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2018-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2002-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/0006-2952(87)90456-4
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1993-11-02 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2004-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2002-02-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90358-1
更新日期：1994-08-30 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：1987-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1990-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02408-5
更新日期：1996-05-17 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90534-7
更新日期：1994-04-29 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90039-l
更新日期：1992-07-07 00:00:00
