title: In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier.
abstract: Natural giant extracellular hemoglobins (Hbs) from polychaete annelids are currently actively investigated as promising oxygen carriers. Their powerful oxygenating ability and their safety have been demonstrated in preclinical studies, motivating their development for therapeutic and industrial applications. HEMARINA-M101 (M101) is derived from the marine invertebrate Arenicola marina. It is formulated as a manufactured product designated HEMOXYCarrier(®) (HEMARINA SA, France). The aim of the present study was to unveil the fate of M101 after a single intravenous (i.v.) injection in mice. For this purpose, M101 was tagged with a far-red fluorescent dye. Repeated non-invasive fluorescent imaging revealed a rapid diffusion of M101 in the whole body of animals, reaching all the examined organs such as brain, liver, lungs and ovaries. Functional M101 was circulating in bloodstream for several hours, without inducing any obvious side-effects. Last, a single i.v. injection of M101 in mice bearing human-derived subcutaneous tumors demonstrated the ability of this Hb to reduce hypoxia in poorly vascularized tissues, thus supporting the biological relevance of M101 oxygen release to vertebrate tissues. Altogether, these results further encourage the development of M101 as an oxygen carrying therapeutic.
authors.affiliation: Unité INSERM 1078, SFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, 46 rue Félix Le Dantec, CS51819, 29218 Brest Cedex 02, France; Plateforme SynNanoVect, SFR 148 ScInBioS, Université de Bretagne Occidentale, Faculté de Médecine, 22 rue Camille Desmoulins, 29200 Brest, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Le Gall
authors.affiliation: HEMARINA SA, Aéropôle centre, Biotechnopôle, 29600 Morlaix, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Polard
authors.affiliation: HEMARINA SA, Aéropôle centre, Biotechnopôle, 29600 Morlaix, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rousselot
authors.affiliation: HEMARINA SA, Aéropôle centre, Biotechnopôle, 29600 Morlaix, France.
authors.forename: Auréline
authors.initials: A
authors.lastname: Lotte
authors.affiliation: Unité INSERM 1030, Radiothérapie Moléculaire, Université Paris XI, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Mouna
authors.initials: M
authors.lastname: Raouane
authors.affiliation: Unité INSERM 1078, SFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, 46 rue Félix Le Dantec, CS51819, 29218 Brest Cedex 02, France; Plateforme SynNanoVect, SFR 148 ScInBioS, Université de Bretagne Occidentale, Faculté de Médecine, 22 rue Camille Desmoulins, 29200 Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.affiliation: Unité de Pathologie Expérimentale, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Paule
authors.initials: P
authors.lastname: Opolon
authors.affiliation: CHRU de Brest, Département de Prothèses, UFR Odontologie, Brest F29238, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Leize
authors.affiliation: Unité INSERM 1030, Radiothérapie Moléculaire, Université Paris XI, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: HEMARINA SA, Aéropôle centre, Biotechnopôle, 29600 Morlaix, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Zal
authors.affiliation: Unité INSERM 1078, SFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, 46 rue Félix Le Dantec, CS51819, 29218 Brest Cedex 02, France; Plateforme SynNanoVect, SFR 148 ScInBioS, Université de Bretagne Occidentale, Faculté de Médecine, 22 rue Camille Desmoulins, 29200 Brest, France; DUMG, Université de Bretagne Occidentale, CHRU de Brest, service de biochimie et de pharmaco-toxicologie, 5 avenue du Maréchal Foch, 29200 Brest, France. Electronic address: Tristan.Montier@univ-brest.fr.
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
mesh_terms: D000818:Animals; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019073:HT29 Cells; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011077:Polychaeta / Q000737:chemistry; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D005456:Fluorescent Dyes; D006454:Hemoglobins; D010100:Oxygen
keywords: Arenicola marina; Biodistribution; Fluorescence; Natural extracellular hemoglobin; Tissue oxygenation