In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster

Abels, Christoph; Heil, P.; Dellian, Marc; Kuhnle, G. E. H.; Baumgartner, Reinhold; Goetz, Alwin E.

doi:10.1038/bjc.1994.406

Cited by 79 publications

(61 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5-Aminolaevulinic acid was administered intravenously in a dose of 500 mg kg À1 b.w. according to previous experiments (Abels et al, 1994(Abels et al, , 1997aSzeimies et al, 1995). The conscious animals did not show any signs of discomfort during injection of the ALA-solution as previously reported by Edwards et al (1984).…”

Section: Animal and Tumour Modelsupporting

confidence: 78%

“…Photodynamic therapy was performed according to previous studies (Abels et al, 1994(Abels et al, , 1997aSzeimies et al, 1995). Since in the literature it is reported that low-dose PDT or fractionated irradiation may be more effective as compared to high-dose PDT or continuous irradiation (Gibson et al, 1990;Messmann et al, 1995;de Bruijn et al, 1999;Iinuma et al, 1999), PDT dosimetry was performed with a light intensity of either 100 or 25 mW cm À2 and light was applied either continuously or fractionated according to the experiments of Curnow et al (2000) and de Bruijn et al (1999).…”

Section: Discussionmentioning

confidence: 99%

“…The animals were randomly assigned to the different groups according to the different protocols: control (I); high-dose PDT (100 mW cm À2 , 100 J cm À2 ), continuous irradiation (II); high-dose PDT (100 mW cm À2 , 100 J cm À2 ), fractionated irradiation (III); lowdose PDT (25 mW cm À2 , 100 J cm À2 ), continuous irradiation (IV); low-dose PDT (25 mW cm À2 , 100 J cm À2 ), fractionated irradiation (V). At the time of highest fluorescence intensity, 150 min after intravenous ALA application (500 mg kg À1 b.w), the irradiation was performed with an incoherent light source (l em ¼ 580 -740 nm, PDT 1200, Waldmann, Germany) as published previously (Abels et al, 1994(Abels et al, , 1997aSzeimies et al, 1995). The light dose of 100 J cm -2 was kept constant in all groups.…”

Section: Photodynamic Therapymentioning

confidence: 99%

“…The endogenous photosensitiser ALA is a haem precursor and induces the synthesis of porphyrins (protoporphyrin IX, PpIX) in mitochondria-containing cells (Williams, 1990). A selectivity of ALA-induced porphyrins is described in neoplastic tissue (Abels et al, 1994;Ackermann et al, 1998;Langer et al, 1999) as well as in malignant cells (Rittenhouse-Diakun et al, 1995) and provides the basis for clinical use of ALA-based photodynamic therapy and diagnosis (Kriegmair et al, 1995). ALA is water soluble and can therefore be administered either systemically (Grant et al, 1993) or topically (Szeimies et al, 1994).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo

et al. 2003

Self Cite

View full text Add to dashboard Cite

To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamsters were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n ¼ 26). PDT was performed (100 mW cm À2 , 100 J cm À2 , continuously or fractionated, and 25 mW cm À2 , 100 J cm À2 ; continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20 J cm À2 for 15 min. Prior to and up to 24 h after PDT tissue, pO 2 was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n ¼ 36). Only high-dose PDT resulted in a significant decrease of pO 2 . Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO 2 . No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.

show abstract

Section: Animal and Tumour Modelsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Photodynamic Therapymentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, investigators have found that exogenous administration of 8-ALA to lesions can induce the accumulation of protoporphyrin IX (PPIX) (Malik and Laguci, 1987; Shoenfeld et al, 1994;Hua et al, 1995), an efficient photosensitizer (Kennedy et al, 1990). In addition, there are reports that accumulation of PPIX is greater in malignant than normal tissues (Dailey and Smith, 1984;Abels et al, 1994;Kriegmeir et al, 1996). These factors make 8-ALA-induced photosensitization an attractive alternative to PDT regimens that use exogenous photosensitizers.…”

mentioning

confidence: 99%

A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolaevulinic acid (δ-ALA)-induced photosensitization?

Gibson

Cupriks²,

Havens³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary As an initial approach to optimize 8-aminolaevulinic acid (6-ALA)-induced photosensitization of tumours, we examined the response of three enzymes of the haem biosynthetic pathway: 8-ALA dehydratase, porphobilinogen deaminase (PBGD) and ferrochelatase. Only PBGD activity displayed a time-and dose-related increase in tumours after intravenous administration of 300 mg kg-1 6-ALA. The time course for porphyrin fluorescence changes, reflecting increased production of the penultimate porphyrin, protoporphyrin IX (PPIX), showed a similar pattern to PBGD. This apparent correlation between PBGD activity and porphyrin fluorescence was also observed in four cultured tumour cell lines exposed to 0.1-2.0 mm 6-ALA in vitro. The increase in PBGD activity and PPIX fluorescence was prevented by the protein synthesis inhibitor cycloheximide. As the apparent Km for PBGD was similar before and after 6-ALA, the increase in PBGD activity was attributed to induction of enzyme de novo. These observations of an associated response of PBGD and PPIX imply that PBGD may be a ratelimiting determinant for the efficacy of 6-ALA-induced photosensitization when used in photodynamic therapy.Keywords: 6-aminolaevulinic acid: photosensitization; porphobilinogen deaminase: haem biosynthesis; porphyrin fluorescence Haem is an essential prosthetic group in many critical cellular proteins such as haemoglobin, cytochrome P450 and cyclooxygenase (Abraham, 1991). Eight enzymes are involved in the biosynthesis of haem, a process that occurs in two subcellular compartments: the mitochondria and the cytosol. The first enzyme in the haem pathway, mitochondrial 8-aminolaevulinic acid synthase (8-ALA-S), forms 6-ALA from glycine and succinyl CoA and is a target for the regulation of haem biosynthesis. Feedback inhibition of 8-ALA-S occurs when intracellular haem is present in excess (Ade, 1990).The last step in the haem biosynthetic pathway, the insertion of iron into PPIX to form haem, is catalysed by the mitochondrial enzyme ferrochelatase (FC). In unperturbed systems, FC is regulated by the availability of iron and/or PPIX. Two of the metabolic events that occur between 8-ALA-S and FC are catalysed by the cytosolic enzymes 8-ALA dehydratase (8-ALA-D) and porphobilinogen deaminase (PBGD). The dehydratase enzyme catalyses the condensation of two 8-ALA molecules to form porphobilinogen (PBG). It is the first enzyme that will metabolize the administered 8-ALA. The next enzyme in haem biosynthesis, PBGD, forms the tetrapyrole ring from four porphobilinogen molecules (Abraham, 1991).By providing the 8-ALA-S product, 8-ALA, the initial feedback step has been circumvented and this approach has been exploited for use in photodynamic therapy (PDT) of cancer (Kennedy and Pottier, 1992;Grant et al, 1993; Cairnduff et al, 1994;Regula et al, 1995). Traditional PDT regimens consist of the systemic adminis- Accepted 13 June 1997 Correspondence to: R Hilf tration of a photosensitizer followed by an appropriate interval to allow for its maximal accumulation in ma...

show abstract

A study of aminolevulinic acid-induced protoporphyrin IX fluorescence kinetics in the canine oral cavity

et al. 2000

View full text Add to dashboard Cite

In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster

Abstract: Summan For successful photodynamic diagnosis (PDD) and effective photodymamic therapy (PDT) with the clinically used 'photosensitiser' 5-aminolaevulinic acid (ALA)

Cited by 79 publications

References 36 publications

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo

A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolaevulinic acid (δ-ALA)-induced photosensitization?

A study of aminolevulinic acid-induced protoporphyrin IX fluorescence kinetics in the canine oral cavity

Contact Info

Product

Resources

About