Distribution of 5-aminolevulinic acid derivatives and induced porphyrin kinetics in mice tissues.
OBJECTIVE
Porphyrins synthesised from 5-aminolevulinic acid (ALA) have been successfully used for the photodiagnosis and photodynamic treatment of cancer. To find a more efficient pro-photosensitiser, we synthesised two ALA esters: R,S-ALA-2-(hydroxymethyl)tetrahydropyranyl ester (THP-ALA) and ALA-Undecanoyl ester (Und-ALA).


METHODS
In mice bearing a subcutaneous mammary adenocarcinoma, we studied the distribution of the porphyrins formed from these esters in tissues after systemic administration, to establish if these esters are retained in any specific tissue, which could potentially be targeted for photodynamic treatment with ALA derivatives. We also investigated the topical use of these esters.


RESULTS
After systemic administration, tumour and skin overlying tumour porphyrin levels were lower from the ALA esters than from ALA. Other tissues such as liver, colon, kidney, skin and spleen also accumulated less porphyrins from the esters, showing that there is no specific retention of the esters in these tissues. However, the brain was the only organ that synthesised more porphyrins from THP-ALA than from ALA. The kinetics of porphyrin synthesis from ALA esters is comparable to those from ALA in almost all tissues, showing that esterases activities are not limiting the availability of the hydrolysed ALA. Both THP-ALA and Und-ALA, applied topically on the skin over the tumour, exhibited higher selectivity than ALA for the site of application, whereas the amount of tumour porphyrin was the same from ALA and THP-ALA but lower from Und-ALA.


CONCLUSIONS
THP-ALA may be useful for the treatment of brain tumours after systemic administration, whereas THP-ALA and Und-ALA may be used more suitable for the treatment of superficial tumours due to their higher selectivity.
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET and Hospital de Clínicas José de San Martín, University of Buenos Aires, Córdoba 2351 1er subsuelo, CP: 1120AAF, Ciudad de Buenos Aires, Argentina.
Gabriela
G
Di Venosa
Alcira
A
Batlle
Haydée
H
Fukuda
Alexander
A
Macrobert
Adriana
A
Casas
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000096:biosynthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
D011166:Porphyrins; D000622:Aminolevulinic Acid