Mechanism Of Tumor Localization And Therapy By Derivatives Of Hematoporphyrin

David Kessel

doi:10.1117/12.942702

19 February 1988 Mechanism Of Tumor Localization And Therapy By Derivatives Of Hematoporphyrin

David Kessel

Proceedings Volume 0847, New Directions in Photodynamic Therapy; (1988) https://doi.org/10.1117/12.942702
Event: Cambridge Symposium on Optics in Medicine and Visual Image Processing, 1987, San Diego, CA, United States

Abstract

The tumor-localizing product HPD (hematoporphyrin derivative) contains both monomer and dimer/oligomer components. The former are potent photosensitizers in cell-free systems and, in some cases, in cell culture. But these porphyrins are poorly retained by neoplastic cells in vivo. Tumor localization derives from the presence, in HPD, of a series of covalently-bound hematoporphyrin dimers and oligomers which are joined by ester and ether linkages. Like many non-localizing porphyrins, these products can bind to circulating low-density lipoprotein and enter cells via LDL receptors. The initial step in tumor localization results from the presence of elevated levels of LDL receptors on the surface of neoplastic cells. But retention of the HP dimer/oligomer fraction results in long-term photosensitization. The preferential dye accumulation in mitochondria cannot be attributed to the presence of specific porphyrin receptors, but may instead result from the ability of the porphyrin dimer/oligomer fraction to undergo a conformational change as a function of its environment. These changes were probed in micellar and pre-micellar systems and the results show the HP dimer/oligomers to have properties not shared by porphyrin monomers.

Citation Download Citation

David Kessel "Mechanism Of Tumor Localization And Therapy By Derivatives Of Hematoporphyrin", Proc. SPIE 0847, New Directions in Photodynamic Therapy, (19 February 1988); https://doi.org/10.1117/12.942702

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