Hematoporphyrin derivative (HPD), a
complex mixture of
porphyrins has been used clinically as a
tumor localizer both for diagnostic and therapeutic purposes. Relative lack of
tumor specific uptake limits widespread clinical application. In an attempt to circumvent this problem, we studied 28
porphyrins with widely differing properties using a transplantable KHJJ mammary
carcinoma in the mouse (Balb C) as a
tumor model. Twenty hours after
porphyrin (P) administration, the
tumor, skin and gastrointestinal tract were excised and the latter lavaged with physiologic saline. Tissue
porphyrin content was assessed visually by red U.V. fluorescence, and by quantitative fluorometric extraction, and photodynamic activity was evaluated in vivo using a tuneable
dye laser emitting red light (615-640 nm). (1) Of the five
porphyrins which were taken up by
tumor tissue, i.e. HPD (
photofrin),
photofrin II, meso-tetra (4-carboxyphenyl)
porphine (
TCPP), tetra
sodium-meso-tetra (4-sulfonatophenyl)
porphine (TPSS), and
uroporphyrin I (UROP I), skin and intestinal fluorescence also was marked with the notable exception of those mice receiving UROP I. (2) UROP I clearly was superior to HPD in this study in that the
tumor to skin
porphyrin content ratio was more than seven times greater than the ratio observed with both HPD and
photofrin II, (3) As no measureable UROP was present in the gut, the
tumor:intestinal P ratio under conditions of assay was for practical purposes infinity. (4) Photodynamic
necrosis in the
tumors of UROP I treated animals was similar to that seen following treatment with HPD. We conclude that UROP I appears the most specific
tumor localizing
porphyrin yet studied. This specificity suggests major potential clinical application both as a diagnostic marker for early mucosal
cancer, and in
photoradiation therapy. Moreover, the prolonged photocutaneous side effects as seen with HPD are unlikely.