BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years. PDT involves administration of a tumor‐localizing photosensitizer or photosensitizer prodrug (5‐aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other than ALA‐derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA‐based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA‐derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA‐based PDT and diagnosis. However, no review updating the clinical data has appeared so far. METHODS A review of recently published data on clinical ALA‐based PDT and diagnosis was conducted. RESULTS Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA‐based PDT have reported promising results, including outstanding cosmetic results. However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors. Topical ALA‐PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA‐PDT also has potential as a treatment for nonneoplastic skin diseases. Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain. The ALA‐derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs. CONCLUSIONS Promising results of ALA‐based clinical PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be made, such as optimization of parameters of ALA‐based PDT and diagnosis; increased tumor selectivity of ALA‐derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems. Cancer 1997; 79:2282‐308. © 1997 American Cancer Society.

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and 2University of Leeds, UK.Summary The distribution among the main fractions of human plasma lipoproteins of a number of porphyrins with different tumour localising ability has been determined by means of ultracentrifugation. A main trend is that the fraction of the dyes that are bound to low density lipoprotein (LDL) increases, and the fraction bound to HSA decreases with decreasing polarity of the dyes. An asymmetric charge distribution, such as in TPPS2a, favours LDL-binding more than expected on the basis of lipophilicity. No correlation between the known tumour localising ability of the drugs tested in the present work and their relative affinity for LDL was found. One of the best tumour localisers reported in the literature, TPPS4, hardly binds to LDL, while Hp and Pp, which are commonly considered inefficient tumour localisers, do have a significant affinity for LDL. On the other hand, the LDL binding capacity for a drug is suggested to be a good index for cellular uptake. Such an index does not necessarily imply that the actual uptake occurs by the LDL pathway.

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