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Nature of the Tumor-localizing Components of Hematoporphyrin Derivative

Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research [P. A. S., R. M. B., G. M.], and The Higginbotham Neurosciences Laboratory [A. H. K.], P. O. Royal Melbourne Hospital, Victoria 3050, Australia

Hematoporphyrin derivative linked by ether bonds (HE) was synthesized by unambiguous procedures in order to compare its properties to hematoporphyrin derivative (HpD). Reverse phase high performance liquid and gel filtration chromatography were used to compare the HE derivatives to HpD. The cellular uptake of HE derivatives was compared to HpD using the WEHI 3B (D⁺) cell line and was shown to be taken up to a degree and in a manner similar to HpD. The efficiency of HE porphyrins as photosensitizers was compared to HpD using the V79 cell line. HE porphyrins were more efficient in sensitizing the V79 cells than was HpD. The in vivo tumor localizing properties of HE porphyrins were compared to HpD in CBA mice bearing the C6 cerebral glioma, and BALB/c mice bearing the EMT6 mammary tumor. HE derivatives localized in both tumor models as effectively as HpD. We conclude that the properties of ether linked hematoporphyrin derivatives are very similar to properties of HpD.

¹ To whom requests for reprints should be addressed.

Received 7/14/86. Revised 12/19/86. Revised 3/31/87. Accepted 4/ 6/87.