FLUORESCENCE AND PHOTODYNAMIC EFFECTS OF BACTERIOCHLORIN A OBSERVED INVIVO IN SANDWICH OBSERVATION CHAMBERS

Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an e ffective photosensitiser in vitro and in vivo. BCA has a major absorpt ion peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensiti vity. The tissue localising and photodynamic properties of BCA were st udied using isogeneic RMA mammary tumours, transplanted into subcutane ous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administr ation of 20 mg kg-1 BCA was assessed in blood vessels, tumour and norm al tissue. Subsequently, the development of vascular- and tissue damag e after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fi fteen minutes post injection (p.i.), the fluorescence of BCA in the tu mour reached a plateau value of 2.5 times the fluorescence in the norm al tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed t hat of the normal tissue. Following photodynamic therapy (PDT), 24 h p .i., complete vascular stasis was observed 2 h post treatment in the t umour only, with subsequent recovery. The presence of viable tumour ce lls following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA -PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and norm al tissue, was sufficient to prevent tumour regrowth. However, this on ly occurred when re-transplantation was performed 7 days after PDT. Du ring PDT, 1 h p.i., vascular damage in tumour and normal tissue was co nsiderable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation dam age was associated with vascular spasm and occlusion probably due to t hrombi formation. Oedema was notable, especially following PDT with 60 0 J cm-2 at 24 h p.i.