thanks, thanks, thanks..... here's some background on the group. Don't have time right now to see if this is the most relevant reference available........|
Br J Cancer 1998 Nov;78(10):1278-82
Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in
normal rat colon using hydroxypyridinone iron-chelating agents.
Curnow A, McIlroy BW, Postle-Hacon MJ, Porter JB, MacRobert AJ, Bown SG
National Medical Laser Centre, Institute of Surgical Studies, University College London Medical School, UK.
Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for photodynamic therapy
(PDT) is limited by the maximum tolerated oral ALA dose (60 mg kg(-1)). This study investigates whether hydroxypyridinone
iron-chelating agents can be used to enhance the tissue levels of PPIX, without increasing the administered dose of ALA.
Quantitative charge-coupled device (CCD) fluorescence microscopy was employed to study PPIX fluorescence
pharmacokinetics in the colon of normal Wistar rats. The iron chelator, CP94, when administered with ALA was found to
produce double the PPIX fluorescence in the colonic mucosa, compared with the same dose of ALA given alone and to be
more effective than the other iron chelator studied, CP20. Microspectrofluorimetric studies demonstrated that PPIX was the
predominant porphyrin species present. PDT studies conducted on the colonic mucosa showed that the simultaneous
administration of 100 mg kg(-1) CP94 i.v. and 50 mg kg(-1) ALA i.v. produced an area of necrosis three times larger than
similar parameters without the iron-chelating agent with the same light dose. It is possible, therefore, to increase the amount of
necrosis produced by ALA-induced PDT substantially, without increasing the administered dose of ALA, through the
simultaneous administration of the iron-chelating agent, CP94.