title: Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy.
abstract: 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.
authors: Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands.
authors: M B
authors: MB
authors: Vrouenraets
authors: G W
authors: GW
authors: Visser
authors: F A
authors: FA
authors: Stewart
authors: M
authors: M
authors: Stigter
authors: H
authors: H
authors: Oppelaar
authors: P E
authors: PE
authors: Postmus
authors: G B
authors: GB
authors: Snow
authors: G A
authors: GA
authors: van Dongen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin