title: Towards matched pairs of porphyrin-Re(I) /(99m) Tc(I) conjugates that combine photodynamic activity with fluorescence and radio imaging.
abstract: We recently prepared two novel water soluble porphyrins bearing a single peripheral chelator, either diethylenetriamine (1) or bipyridyl (2), tethered to one meso position. The preparation of their conjugates with a fac-{(99m) Tc(CO)3 }(+) fragment and the potential of these resulting conjugates as fluorescence and radio imaging tools were also described. In this work, we focused on the corresponding non-radioactive analogues that bear the fac-{Re(CO)3 }(+) fragment (diethylenetriamine 3 and bipyridyl 4). We report on the uptake, in vitro PDT activity, and cellular localization of Re(I) conjugates 3 and 4 in comparison to the parent porphyrins 1 and 2. Compounds 1-4 have modest or negligible cytotoxicity in the dark against HeLa human cervical cancer cells but become remarkably cytotoxic after exposure to moderate doses of red visible light (590-700 nm). This phototoxicity was found to be directly proportional to the total light dose. Although the four compounds show distinct uptake patterns, they have comparable PDT activity. Confocal fluorescence measurements showed that porphyrin 1 and its Re(I) conjugate 3 have different cellular localization patterns in HeLa cells.
authors.affiliation: Department of Chemical & Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste (Italy).
authors.forename: Teresa
authors.initials: T
authors.lastname: Gianferrara
authors.forename: Cinzia
authors.initials: C
authors.lastname: Spagnul
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
authors.forename: Gilles
authors.initials: G
authors.lastname: Gasser
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pierroz
authors.forename: Alberta
authors.initials: A
authors.lastname: Bergamo
authors.forename: Enzo
authors.initials: E
authors.lastname: Alessio
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008027:Light; D018613:Microscopy, Confocal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry*; D011789:Quantum Theory; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D011166:Porphyrins; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium
keywords: imaging; matched pair strategy; photodynamic therapy; porphyrin conjugates; rhenium(I); technetium(I)