Cited by 198Photodynamic Therapy Research StudiesPorphyrin Metabolism and DisordersNanoplatforms for cancer theranostics

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Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats

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Van Hillegersberg, Richard, Van Den Berg, J.Willem O., Kort, Will J., Terpstra, Onno T., Wilson, J.H.Paul·1992·Gastroenterology

DOI 10.1016/0016-5085(92)90860-2

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Abstract

The possibility of using the porphyrin precursor 5-aminolevulinic acid to cause selective porphyrin accumulation in tumors was examined. Syngeneic colon carcinomas CC531 were implanted in the livers of Wag/Rij rats. Groups of three to six animals each were given 2 mg/mL of 5-aminolevulinic acid in drinking water from the 8th, 14th, or 17th day after tumor implantation. Two other groups received either 2.5 or 5 mg/kg of Photofrin II (Photomedica Inc., Raritan, NJ) intravenously on day 17. On day 19 the livers were removed and porphyrin concentrations were measured in normal livers and tumors by solvent extraction and high-performance liquid chromatography. Protoporphyrin accumulated progressively in tumors with increasing duration of 5-aminolevulinic acid administration (P = 0.0001), whereas no increase was found in normal livers. After 11 days of 5-aminolevulinic acid administration the porphyrin concentration ratio between tumors and livers was 4:1. In contrast, after Photofrin II administration the concentration was higher in normal livers than in tumors (1:3 ratio, tumor to liver). Enzyme measurements showed a threefold decrease in ferrochelatase activity in tumors compared with livers (P less than 0.001). In conclusion, oral administration of 5-aminolevulinic acid results in progressive accumulation of protoporphyrin in a transplantable colon carcinoma without accumulation in the surrounding liver tissue. This selective accumulation of porphyrins appears to be caused by a relative ferrochelatase deficiency in malignant tissue. 5-Aminolevulinic acid administration may be a suitable approach to photosensitizing liver tumors for photodynamic therapy or to early detection of tumors by fluorescence in ultraviolet light.

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Authors: Van Hillegersberg, R., Van Den Berg, J. W. O., Kort, W. J., Terpstra, O. T., & Wilson, J. H. P.
Affiliations: Erasmus MC (NL)
Erasmus University Rotterdam (NL)
ORCID: Van Hillegersberg, Richard
Wilson, J.H.Paul
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 1992-08
Volume: 103
Issue: 2
Pages: 647-651
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1016/0016-5085(92)90860-2
OpenAlex: W1610046461
Cited by: 198
References: 29
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 1 · 2012: 4
FWCI: 7.64
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords: 5-aminolevulinic acid, porphyrin accumulation, protoporphyrin IX, liver metastasis, colon cancer, ferrochelatase deficiency, Photofrin II, photodynamic therapy, photosensitizers, oral administration
MeSH terms: Aminolevulinic Acid, Animals, Disease Models, Animal, Ferrochelatase, Hematoporphyrins, Liver Neoplasms, Experimental, Hydroxymethylbilane Synthase, Porphyrins, Dihematoporphyrin Ether, Rats

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Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats

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