Claims
- 1. Method for detecting or locating mammalian tumor cells by increasing the porphyrin content of said mammalian tumor cells in mammalian tissue and examining said mammalian tissue under porphyrin-stimulating light and observing the fluorescence from the tumor, which comprises treating an organism comprising said mammalian tumor cells with a compound which is a specific inhibitor of the enzymatic conversion of protoporphyrinogen to heme in mammalian cells and which is not a tetrapyrrole thereby causing a buildup of protoporhyrin IX in said mammalian tumor cells.
- 2. Method as in claim 1 in which said compound is a specific inhibitor of the enzymatic conversion of protoporphyrinogen to protoporphyrin IX by protoporphyrinogen oxidase.
- 3. Method as in claim 2 in which said compound has a redox potential more negative than -500 mV.
- 4. Method as in claim 2 in which said compound has an l.sub.50 for protoporhyrinogen oxidase of less than about 10 .mu.M.
- 5. Method as in claim 4 in which said l.sub.50 is less than about 1 .mu.M.
- 6. Method as in claim 2 in which said compound is a nitrodiphenyl ether herbicide.
- 7. Method as in claim 6 in which said nitrodiphenyl ether has a carboxylic acid ester substituent.
- 8. Method as in claim 7 in which said substituent is a carboethoxyethyl or carboethoxymethyl substituent.
- 9. Method as in claim 6 in which said nitrodiphenyl ether has an ethoxy or methoxy substituent.
- 10. Method as in claim 2 in which said compound has the formula Ph--NHet where "Ph" is a substituted phenyl and NHet is a 5- or 6-membered heterocyclic ring having one to four ring-nitrogen atoms and having the formula
- where Q represents the balance of the heterocyclic ring and R represents hydrogen or a substituent group.
- 11. Method as in claim 2 in which said compound has the formula ##STR14## where Ph is substituted phenyl.
- 12. Method as in claim 2 in which said compound has the formula ##STR15## where Ph is substituted phenyl.
- 13. Method as in claim 10 in which Ph is phenyl having a substituent of the formula ##STR16## where R is lower alkyl.
- 14. Method as in claim 10 in which Ph is phenyl having a substituent which includes a terminal 1-(lower alkoxycarbonyl)ethoxy group.
- 15. Method as in claim 10 in which said substituent is a phenoxy substituent.
- 16. Method as in claim 2 in which a mammal having a solid tumor is treated with said compound, after which the tumor is subjected to the porphyrin-stimulating light.
- 17. Method as in claim 16 in which said treatment with said compound comprises oral administration of said compound to said mammal.
- 18. Method as in claim 17 in which said compound is a water-soluble salt or an acidic compound whose sodium salt is water soluble.
- 19. Method as in claim 10 in which said compound is an aryl triazolinone, an aryl tetrazolinone, an aryl triazinedione, an aryl oxadiazole, an aryl tetrahydroindazole, an aryl tetrahydrophthalimide, an aryl hydantoin, an aryl urazole, an aryl hexahydropyridazine, an aryl pyrazole, an aryl imidazolopyrimidine, an aryl pyridyldiazine, an aryl diazinedione, an aryl pyradiazinone, an aryl oxadiazolinone, an aryl oxadiazinone, an aryl benzamidazole, an aryl iminotriazolopyridazine, an aryl thiazole, or an aryl pyrrole.
- 20. Method as in claim 2 in which said compound is ##STR17##
- 21. Method as in claim 2 in which said compound is ##STR18##
Parent Case Info
This application is a division of application Ser. No. 814,305, filed Dec. 23, 1991, now U.S. Pat. No. 5,298,502, which is a continuation-in-part of application Ser. No. 622,303, filed Dec. 5, 1990, abandoned, which is a continuation-in-part of application Ser. No. 535,076, filed Jun. 8, 1990, abandoned, which is a continuation-in-part of application Ser. No. 351,331, filed May 3, 1989, abandoned, which is a continuation-in-part of application Ser. No. 335,007, filed Apr. 7, 1989, abandoned, which is a continuation-in-part of application Ser. No. 285,151, filed Dec. 12, 1988, abandoned.
US Referenced Citations (3)
Non-Patent Literature Citations (5)
Entry |
El-Far et al. "Selective in Vivo Tumor Localization of Uroporphyrin Isomer I in Mouse Mammary Carcinoma: Superiority over Other Porphyrins in a Comparative Study" Cancer Res 46:4390-4394 1986. |
Mang et al. "Fluorescence Detection of Tumors" Cancer 71(1):269-276 1993. |
Goff et al. "Effects of Photodynamic Therapy with Topical Application of 5-Aminolevulinic acid on normal skin of hairless guinea pigs" J Photochem Photobiol B:Biol 15:239-251 1992. |
Camadro et al. "Kinetic Properties of Membrane Bound Human Liver Mirochondrial Protoprophyrinogen Oxidase" Arch Biochem Biophys 242(1):206-212 1985. |
H. A. Dailey et al., "Bovine Ferrochelatase", J. Biol. Chem., vol. 258, pp. 11453-11456 (1983). |
Divisions (1)
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Number |
Date |
Country |
Parent |
814305 |
Dec 1991 |
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Continuation in Parts (5)
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Number |
Date |
Country |
Parent |
622303 |
Dec 1990 |
|
Parent |
535076 |
Jun 1990 |
|
Parent |
351331 |
May 1989 |
|
Parent |
335007 |
Apr 1989 |
|
Parent |
285151 |
Dec 1988 |
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