Distribution of pheophorbide A in normal tissues and in an experimental pancreatic cancer in rats.
The in vivo administration and distribution of a potent new photosensitizer, pheophorbide A (PH-A), was investigated in rats. The spectral characteristics were determined. This hydrophobic compound was solubilized by an ethanol/phosphate-buffered saline (PBS) mixture (v/v) and sonicated immediately before i.v. administration. Tissue distribution and the affinity of PH-A for an acinar pancreatic tumor were determined in Lewis rats for up to 48 h after a single i.v. administration of 3 mg kg-1 body wt. Methanol-extracted PH-A was quantitatively determined by fluorescence spectrophotometry at 665.6 nm. The PH-A uptake pattern showed that the reticulo-endothelial system is the major target of PH-A, followed by the gut and then the lung and pancreas. PH-A concentrations in skin were very low. The presence of an enterohepatic cycle was suggested by the PH-A biliary output, intestinal uptake and blood concentrations. Tumor PH-A retention was longer than pancreatic retention. The ratio of tumoral to peri-tumoral pancreas PH-A was 6.7:1, 24 h after i.v. administration. With its similar tissue pattern, better absorption spectrum and lower skin toxicity, PH-A could be a more potent photosensitizer than hematoporphyrin derivatives.
INSERM, Unit 61, Digestive Cell Biology and Physiopathology, Strasbourg, France.
M
M
Aprahamian
S
S
Evrard
P
P
Keller
M
M
Tsuji
G
G
Balboni
C
C
Damgé
J
J
Marescaux
D000818:Animals; D002734:Chlorophyll / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000493:pharmacokinetics*; D051381:Rats; D011917:Rats, Inbred Lew; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll; C032623:pheophorbide a