Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy

Cancer Res. 1999 Apr 1;59(7):1505-13.


A limitation of photodynamic therapy is the lack of tumor selectivity of the photosensitizer. To overcome this problem, a protocol was developed for coupling of meta-tetrahydroxyphenylchlorin (mTHPC), one of the most promising photosensitizers, to tumor-selective monoclonal antibodies (MAbs). mTHPC was radiolabeled with 131I to facilitate the assessment of the in vitro and in vivo behavior. After the modification to 131I-mTHPC-(CH2COOH)4, thus increasing the water solubility and creating a functional moiety suitable for coupling, conjugation was performed using a labile ester. Insoluble aggregates were not formed when mTHPC-MAb conjugates with a molar ratio of up to 4 were prepared. These conjugates showed a minimal impairment of the integrity on SDS-PAGE, full stability in serum in vitro, and an optimal immunoreactivity. To test the in vivo behavior of the mTHPC-MAb conjugates, the head and neck squamous cell carcinoma-selective chimeric MAb U36 was used in head and neck squamous cell carcinoma-bearing nude mice. Biodistribution data showed that the tumor selectivity of cMAb U36-conjugated mTHPC was increased in comparison with free mTHPC, despite the fact that conjugates with a higher mTHPC:MAb ratio were more rapidly cleared from the blood. Preliminary results on the in vitro efficacy of photodynamic therapy with MAb-conjugated mTHPC showed that mTHPC coupled to the internalizing murine MAb 425 exhibited more phototoxicity than when coupled to the noninternalizing chimeric MAb U36.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Humans
  • Immunoconjugates / therapeutic use*
  • Iodine Radioisotopes
  • Mesoporphyrins / pharmacokinetics
  • Mesoporphyrins / therapeutic use*
  • Mice
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Tissue Distribution
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Immunoconjugates
  • Iodine Radioisotopes
  • Mesoporphyrins
  • Photosensitizing Agents
  • temoporfin