title: Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis.
abstract: Chemotherapy-induced enteropathy (CIE) is one of the most serious complications of anticancer therapy, and tools for its early detection and monitoring are highly needed. We report on a novel fluorescence method for detection of CIE, based on molecular imaging of the related apoptotic process. The method comprises systemic intravenous administration of the ApoSense fluorescent biomarker (N,N(')-didansyl-L-cystine DDC) in vivo and subsequent fluorescence imaging of the intestinal mucosa. In the reported proof-of-concept studies, mice were treated with either taxol+cyclophosphamide or doxil. DDC was administered in vivo at various time points after drug administration, and tracer uptake by ileum tissue was subsequently evaluated by ex vivo fluorescent microscopy. Chemotherapy caused marked and selective uptake of DDC in ileal epithelial cells, in correlation with other hallmarks of apoptosis (i.e., DNA fragmentation and Annexin-V binding). Induction of DDC uptake occurred early after chemotherapy, and its temporal profile was parallel to that of the apoptotic process, as assessed histologically. DDC may therefore serve as a useful tool for detection of CIE. Future potential integration of this method with fluorescent endoscopic techniques, or development of radio-labeled derivatives of DDC for emission tomography, may advance early diagnosis and monitoring of this severe adverse effect of chemotherapy.
authors.affiliation: Aposense Ltd., 5 Ha'Odem Street, P.O. Box 7119, Petach-Tiqva 49170, Israel.
authors.forename: Galit
authors.initials: G
authors.lastname: Levin
authors.forename: Anat
authors.initials: A
authors.lastname: Shirvan
authors.forename: Hagit
authors.initials: H
authors.lastname: Grimberg
authors.forename: Ayelet
authors.initials: A
authors.lastname: Reshef
authors.forename: Merav
authors.initials: M
authors.lastname: Yogev-Falach
authors.forename: Avi
authors.initials: A
authors.lastname: Cohen
authors.forename: Ilan
authors.initials: I
authors.lastname: Ziv
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects; D003553:Cystine / Q000031:analogs & derivatives*; D003619:Dansyl Compounds; D007078:Ileal Neoplasms / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques; D017239:Paclitaxel
chemical_list: D000970:Antineoplastic Agents; D003619:Dansyl Compounds; C038494:di(dansyl)cystine; D003553:Cystine; D017239:Paclitaxel