(Z)-1,4-diamino-2-butene as a vector of boron, fluorine, or iodine for cancer therapy and imaging: synthesis and biological evaluation.
Polyamine vectors are attractive for tumor targeting. We envisaged (Z)-1,4-diamino-2-butene (Z-DAB), an unsaturated analogue of putrescine as vector of (10)B, (18)F and (131)I for boron neutron capture therapy (BNCT), and tumor imaging by positron emission tomography or scintigraphy respectively. In the present work, the synthesis and characterization of new derivatives of Z-DAB were reported. Z-DAB was actively transported in cells via the polyamine transport system and converted into the spermidine analogue.(E)-2-iodo-1,4-diamino-2-butene (E-I-DAB) was not taken up by the polyamine transport system and may not be suitable for tumor imaging. In contrast, (Z)-2-[4-(5,5-dimethyl-dioxaborinan-2-yl)phenyl]methyl-1,4-diamino-2-butene (Z-4-Bbz-DAB) was a substrate of the transport system and allowed significant boron accumulation in 3LL cells. Its potential in BNCT will be evaluated.
Groupe de Recherche en Thérapeutiques Anticancéreuses, CNRS FRE 2261, Faculté de Médecine, 2, Avenue du Pr. Léon Bernard, F35043 cedex, Rennes, France
Bénédicte
B
Martin
Françoise
F
Possémé
Caroline
C
Le Barbier
François
F
Carreaux
Bertrand
B
Carboni
Nikolaus
N
Seiler
Jacques-Philippe
JP
Moulinoux
Jean-Guy
JG
Delcros
D000818:Animals; D001692:Biological Transport; D001895:Boron / Q000627:therapeutic use; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005462:Fluorine Radioisotopes / Q000627:therapeutic use; D006219:Halogens / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011868:Radioisotopes / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D005462:Fluorine Radioisotopes; D006219:Halogens; D007457:Iodine Radioisotopes; D011073:Polyamines; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C021006:diaminobutene; D001895:Boron; D011700:Putrescine