title: Characterization of the Biodistribution and Systemic Absorption of TT-173, a New Hemostatic Agent of Recombinant Human Tissue Factor, Using Radiolabeling with 18F.
abstract: OBJECTIVE
  TT-173 is the first topical hemostatic agent based on tissue factor. To prevent thromboembolic events and intravascular coagulation it is necessary to rule out the systemic absorption of new bioactive hemostats. Here, we radiolabeled TT-173 with [18F]SBF to characterize its systemic absorption and biodistribution.
  
  
  METHODS
  A group of rats were administered intravenously with [18F]TT-173 and were subjected to a positron emission tomography study. A second group of animals received the [18F]TT-173 topically over a skin lesion in the flank. Topical absorption was quantified and the biodistribution patterns observed were compared.
  
  
  RESULTS
  After topical application, low amounts of [18F]TT-173 were absorbed and distributed without relevant accumulation in any organ. On the other hand, after intravenous injection, [18F]TT-173 accumulated in lungs, liver and spleen, consistent with intravascular clot formation and the posterior capillary trapping and phagocytosis by the reticuloendothelial system. In both cases, a substantial concentration of radioactive product was found in urine consistent with renal excretion of degradation products of [18F]TT-173.
  
  
  CONCLUSIONS
  After topical application, [18F]TT-173 did not show a significant systemic accumulation in animal organs. Minor radioactive concentration found in lungs, liver and spleen likely corresponds with fragments of the product without procoagulant activity. Radiolabeling with [18F]SFB enables the characterization of systemic absorption and biodistribution of new topical hemostats like TT-173.
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain. santiagorojas@thrombotargets.com.|Unit of Human Anatomy and Embryology, Department of Morphological Sciences, Faculty of Medicine, Autonomous University of Barcelona, Cerdanyola Del Vallès, Spain. santiagorojas@thrombotargets.com.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rojas
authors.affiliation: Molecular Imaging Research Group-Vall d'Hebron Research Institute, CIBBIM-Nanomedicine, Barcelona, Spain. raul.herance@vhir.org.|Centro de Investigaci on Biom edica en Red de Bioingenierıa, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain. raul.herance@vhir.org.
authors.forename: José Raúl
authors.initials: JR
authors.lastname: Herance
authors.affiliation: Barcelonabeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.|Centro de Investigaci on Biom edica en Red de Bioingenierıa, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.|Pompeu Fabra University, Barcelona, Spain.
authors.forename: Juan Domingo
authors.initials: JD
authors.lastname: Gispert
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Arias
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Miquel
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: López
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Rincón
authors.affiliation: Thrombotargets Europe S.L., Mediterranean Technology Park, Av. Canal Olímpic, s/n, Edif, B 6, 2ª, Castelldefels, 08860, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Murat
mesh_terms: D065567:Absorption, Physiological; D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport; D005462:Fluorine Radioisotopes; D006490:Hemostatics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D013925:Thromboplastin / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D006490:Hemostatics; D019275:Radiopharmaceuticals; D013925:Thromboplastin