Reddi E, Segalla A, Jori G, Kerrigan P K, Liddell P A, Moore A L, Moore T A, Gust D
Department of Biology, University of Padova, Italy.
Br J Cancer. 1994 Jan;69(1):40-5. doi: 10.1038/bjc.1994.6.
The covalent binding of a carotene moiety to one phenyl ring and meso-tetraphenyl-substituted porphyrins (see Figure 1) efficiently quenches the photosensitising activity of the porphyrin while a relatively large yield of fluorescence emission around 650 nm is retained. Pharmacokinetic studies performed with two carotenoporphyrins (CPs) and the corresponding porphyrins (Ps) in Balb/c mice bearing an MS-2 fibrosarcoma show that the two Ps give a high selectivity of tumour localisation (tumour/peritumoral tissue ratios of dye concentration ranging between c. 30 and 90 at 24 h after injection of 4.2-8.4 mumol kg-1 in a Cremophor emulsion) and photosensitive tumour necrosis upon red light irradiation. For the same injected doses, the two CPs show no tumour-photosensitising activity even though they localise in the tumour in concentrations of the order of 10-40 micrograms g-1 at 24 h with tumour/peritumoral ratios larger than 10. Thus, the fluorescence emitted by these CPs in the tumour can be used for photodiagnostic purposes with no risk of skin photosensitisation. However, this approach is presently limited by the large accumulation and prolonged retention of the CPs in the liver and spleen.
胡萝卜素部分与一个苯环以及中位四苯基取代卟啉（见图1）的共价结合有效地淬灭了卟啉的光敏活性，同时在650nm左右保留了相对较高产率的荧光发射。在携带MS - 2纤维肉瘤的Balb/c小鼠中，对两种胡萝卜素卟啉（CPs）和相应的卟啉（Ps）进行的药代动力学研究表明，两种Ps具有很高的肿瘤定位选择性（在以聚氧乙烯蓖麻油乳剂形式注射4.2 - 8.4μmol kg-1后24小时，染料浓度的肿瘤/瘤周组织比在约30至90之间），并且在红光照射下会导致光敏性肿瘤坏死。对于相同的注射剂量，两种CPs即使在24小时时以10 - 40μg g-1的浓度在肿瘤中定位且肿瘤/瘤周比大于10，也没有肿瘤光敏活性。因此，这些CPs在肿瘤中发出的荧光可用于光诊断目的，而不存在皮肤光敏的风险。然而，目前这种方法受到CPs在肝脏和脾脏中大量积累和长时间滞留的限制。
