Distribution and Elimination of Photofrin Ii in Mice

Abstract

The distribution and elimination of [14C]PII, the radioisotopically-labeled equivalent of the mixture of porphyrins known as Photofrin II used in the photodynamic treatment of solid tumors, were determined in tumor-free and SMT-F tumor-bearing DBA/2 Ha-DD mice. Following i.p. injection, drug was absorbed from the peritoneum with a half-life of about 1 h; elimination from plasma was rapid, declining about 1.4 logs in concentration over 48 h following i.v. administration. However, some [14C]-activity was still detectable after 75 days. Normal tissues take up the drug within about 7.5 h after administration, with peak concentrations distributed as follows: liver, adrenal gland, urinary bladder greater than pancreas, kidney, spleen greater than stomach, bone, lung, heart greater than muscle much greater than brain. Only skeletal muscle, brain, and skin located contralaterally to subcutaneously implanted SMT-F tumors had peak [14C]-activities lower than tumor tissue; skin overlying SMT-F tumors showed concentrations not significantly different (P greater than 0.3) from tumor. After 75 days all tissues examined retained some fraction of [14C]-activity, ranging from 16% for kidney to 61% for spleen, of the initial peak tissue levels. The primary route of elimination of Photofrin II was through the bile-gut pathway, with greater than 59% of the administered [14C]-activity recovered in the feces, and only about 6% in the urine, over 192 h. HPLC analyses of fecal extracts showed that mostly monomeric and other low molecular weight porphyrin components of Photofrin II were eliminated. The higher molecular weight oligomeric fractions of Photofrin II were retained in liver and spleen up to 14 days after injection.

Carotenoporphyrins as selective photodiagnostic agents for tumours

“…administration. On the other hand, some interesting features are the fast elimination of the carotenoporphyrins from serum, as compared with the persistence of appreciable amounts of Photofrin in mouse serum for several weeks (Bellnier et al, 1989), as well as the notably low amounts of dye which were found in muscle and skin throughout our observation period.…”

Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration

“…administration, although absolute drug concentrations were higher in some organs (liver and kidney) after i.v. administration (Bellnier et al, 1989;Peng et al, 1991). Photofrin levels in the bladder were not measured in these studies.…”

“…Detectable levels of the fluorescent component of Photofrin were, however, present in the normal bladder for up to 10 days. Drug uptake and distribution studies in mice have also demonstrated a slow clearance of these sensitisers from other normal tissues (Peng et al, 1991;Bellnier et al, 1989), with detectable drug levels in muscle, skin, heart, lung, spleen, kidney and liver at 75 days after injection of 5 mg kg-' Photofrin (Bellnier et al, 1989). Several studies have also demonstrated longer elimination times for Photofrin (plasma and tissue) after i.p.…”

Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

“…Selectivity of PDT depends on both photosensitizer localization in tissue and light administration, which makes it important to determine photosensitizer distribution in target tissue and its surrounding tissue. In case of a tumour in a highly vascularized organ as the liver, it will be difficult to reach selective drug uptake, as most photosensitizers are efficiently accumulated in liver tissue (Bown et al, 1986;Bellnier et al, 1989). Only for endogenously generated protoporphyrin-IX, after aminolaevulinic acid (ALA) administration, tumour selectivity has been reported, with tumour to liver ratio of 4:1 (Hillegersberg et al, 1992).…”