title: In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease.
abstract: As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohn's disease led to detection of intestinal mTNF(+) immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF(+) cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF(+) cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn's disease and autoimmune or inflammatory disorders.
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Raja
authors.initials: R
authors.lastname: Atreya
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Neumann
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Neufert
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Maximilian J
authors.initials: MJ
authors.lastname: Waldner
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Billmeier
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Yurdagül
authors.initials: Y
authors.lastname: Zopf
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Willma
authors.affiliation: Department of Biochemistry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: App
authors.affiliation: Department of Anesthesiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Münster
authors.affiliation: Department of Surgery, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Kessler
authors.affiliation: Center for Clinical Studies, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Maas
authors.affiliation: Center for Clinical Studies, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gebhardt
authors.affiliation: Department of Pharmacy, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Heimke-Brinck
authors.affiliation: Department of Pharmacy, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Reuter
authors.affiliation: Department of Pharmacy, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dörje
authors.affiliation: Department of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tilman T
authors.initials: TT
authors.lastname: Rau
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Uter
authors.affiliation: Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wang
authors.affiliation: Medical Clinic, St. Mary's Hospital, Frankfurt, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kiesslich
authors.affiliation: Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Department of Biochemistry, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ewald
authors.initials: E
authors.lastname: Hannappel
authors.affiliation: Medical Clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry; D003424:Crohn Disease / Q000378:metabolism* / Q000628:therapy*; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab