5-Aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain.
A new approach in photodynamic therapy is the use of endogenous porphyrins for sensitisation of tumours to light. The induction of endogenous porphyrins after intravenous injection of 5-aminolevulinic acid (ALA, 200 mg kg-1) was studied in 23 rats, bearing intracranial 9L or C6 tumours. After 0, 2, 4, 6, 8, and 22 hours the rats were sacrificed and the fluorescence distribution of endogenous porphyrins was studied in brain tissue sections with a standard fluorescence microscope and a confocal laser scanning microscope. The role of blood-brain barrier disruption on porphyrin production was studied in 2 rats with a cryo-lesion of the cortex. Additionally, 9L and C6 tumour cell cultures were incubated with ALA for 8 hours in vitro. Fluorescence was measured with a fluorescence spectrophotometer in cell cultures and in the brain sections. Porphyrins were detected in vitro in the tumour cells from 2 hours onwards and ex vivo in the tumour sections mainly from 2 to 8 hours, by 22 hours porphyrin fluorescence had almost disappeared. The contralateral brain showed low fluorescence levels between 2 and 6 hours after ALA administration. At the site of the cryo-lesions low fluorescence was measured 6 hours after ALA administration. The 9L tumours fluoresced homogeneously, with a sharp demarcation towards normal brain tissue. Fluorescence in the C6 tumours was patchy, with a poorly fluorescing edge. In both tumour models fluorescence was also detected in brain surrounding the tumour and sometimes in contralateral white matter and ventricle ependyma and pia mater. The slight increase of porphyrin fluorescence in the normal brain of tumour bearing rats, compared to the absence of this in rats without a tumour, was attributed to transport by bulk flow of porphyrins made in the tumours, and possibly also of circulating porphyrins or ALA leaking from the tumour vessels.
Hebeda
K M
KM
Laser Center, Academic Medical Center, Amsterdam, The Netherlands.
Saarnak
A E
AE
Olivo
M
M
Sterenborg
H J
HJ
Wolbers
J G
JG
D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D018316:Gliosarcoma / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation
D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid