van Leengoed H L, Schuitmaker J J, van der Veen N, Dubbelman T M, Star W M
Dr Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands.
Br J Cancer. 1993 May;67(5):898-903. doi: 10.1038/bjc.1993.168.
Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells 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 normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm and occlusion probably due to thrombi formation. Oedema was notable, especially following PDT with 600 J cm-2 at 24 h p.i.
细菌叶绿素a（BCA）是细菌叶绿素a的衍生物，在体外和体内均为有效的光敏剂。BCA在760nm处有一个主要吸收峰，此时组织穿透性最佳。这一特性与快速的组织清除相结合，有望使皮肤光敏性降低。使用同基因RMA乳腺肿瘤研究了BCA的组织定位和光动力特性，该肿瘤被移植到WAG/Rij大鼠背部透明“三明治”观察室的皮下组织中。静脉注射20mg/kg BCA后，评估血管、肿瘤和正常组织中的荧光动力学。随后，观察治疗光剂量（760nm，600J/cm²）后血管和组织损伤的发展情况。注射后15分钟（p.i.），肿瘤中BCA的荧光达到平台值，是正常组织中荧光的2.5倍。注射后1小时起，肿瘤荧光逐渐减弱；24小时后，肿瘤荧光信号不超过正常组织。光动力疗法（PDT）后，注射后24小时，仅在肿瘤中观察到治疗后2小时出现完全血管淤滞，随后恢复。通过组织学检查以及将治疗后的肿瘤组织立即或在治疗后7天从观察室重新移植到侧腹来评估PDT后存活肿瘤细胞的存在情况。在这两种情况下均观察到肿瘤再生长。BCA给药1小时后进行BCA-PDT（20mg/kg，760nm，100J/cm²），该时间间隔可使肿瘤与正常组织之间产生最佳差异，足以防止肿瘤再生长。然而，这仅在PDT后7天进行重新移植时才会发生。在PDT期间，注射后1小时，肿瘤和正常组织中的血管损伤相当严重。治疗后2小时在肿瘤中观察到完全血管关闭，24小时在周围组织中观察到。循环损伤与血管痉挛和阻塞有关，可能是由于血栓形成。水肿明显，尤其是在注射后24小时用600J/cm²进行PDT后。
