An evaluation of exogenous application of protoporphyrin IX and its dimethyl ester as a photodynamic diagnostic agent in poorly differentiated human nasopharyngeal carcinoma.
5-Aminolevulinic acid and its esterified analogues have been under much investigation to enhance the endogenous production of protoporphyrin IX (PpIX) in tumor cells. However, in this work, we studied the in vitro and in vivo efficacy of exogenously administered PpIX and its esterified analogue, PpIX dimethyl ester (PME), in poorly differentiated human nasopharyngeal carcinoma (NPC/CNE-2) as a photodynamic diagnostic (PDD) agent. NPC/CNE-2 at its earliest time, 1 h after incubation with PME in in vitro studies, has exhibited 64% (P <0.01) higher tumor to normal cell (T/N) fluorescence ratio than with PpIX. In an in vivo mouse xenograft model, comparable photosensitizer concentration in tumor after intravenous administration was observed at 1-3 h time points, but at 9 h, PME had 31% (P=0.05) greater concentration in tumor compared with PpIX. In addition, by constituting PME and PpIX in different topical gel composites, of which, PME gel composition of 8:2 Plasdone and Gantrez resulted in the highest T/N ratio at 6 h after application (34%; P <0.05) in comparison with other gel composites. Evaluation of PME and PpIX constituted in the delivery vehicles investigated showed comparable selectivity for tumor at 1-3 h, thus neither photosensitizer is more efficient than the other for PDD at the early time points; however, beyond 6 h, PME had higher selectivity for tumor compared with PpIX. Thus, further investigation is warranted to improve the drug delivery vehicle for greater tumor selectivity at a shorter incubation time.
Division of Medical Sciences, National Cancer Centre, Singapore 169610, Singapore.
Vanaja
V
Tammilmani
Karen Kar Lye
KK
Yee
Paul Wan Sia
PW
Heng
Khee Chee
KC
Soo
Malini
M
Olivo
D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004952:Esters / Q000737:chemistry*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008745:Methylation; D051379:Mice; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009368:Neoplasm Transplantation / Q000473:pathology; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry
D004952:Esters; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C028025:protoporphyrin IX