title: In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe.
abstract: We aimed to evaluate a fluorescent-labeled single chain variable fragment (scFv) of the anti-PSMA antibody as a specific probe for the detection of prostate cancer by in vivo fluorescence imaging. An orthotopic model of prostate cancer was generated by injecting LNCaP cells into the prostate lobe. ScFvD2B, a high affinity anti-PSMA antibody fragment, was labeled using a near-infrared fluorophore to generate a specific imaging probe (X770-scFvD2B). PSMA-unrelated scFv-X770 was used as a control. Probes were injected intravenously into mice with prostate tumors and fluorescence was monitored in vivo by fluorescence molecular tomography (FMT). In vitro assays showed that X770-scFvD2B specifically bound to PSMA and was internalized in PSMA-expressing LNCaP cells. After intravenous injection, X770-scFvD2B was detected in vivo by FMT in the prostate region. On excised prostates the scFv probe co-localized with the cancer cells and was found in PSMA-expressing cells. The PSMA-unrelated scFv used as a control did not label the prostate cancer cells. Our data demonstrate that scFvD2B is a high affinity contrast agent for in vivo detection of PSMA-expressing cells in the prostate. NIR-labeled scFvD2B could thus be further developed as a clinical probe for imaging-guided targeted biopsies.
authors.affiliation: CNRS UMS 3428 and Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux.
authors.forename: Claire
authors.initials: C
authors.lastname: Mazzocco
authors.affiliation: Department of Medicine, Verona University, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Fracasso
authors.affiliation: CNRS UMS 3428 and Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux.
authors.forename: Coralie
authors.initials: C
authors.lastname: Germain-Genevois
authors.affiliation: Service d'Histologie INSERM US005, Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dugot-Senant
authors.affiliation: Molecular Therapies Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Figini
authors.affiliation: Department of Medicine, Verona University, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colombatti
authors.affiliation: Service d'Imagerie Diagnostique et Interventionnelle de l'Adulte, Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon - F 33076 BORDEAUX Cedex.|Univ. Bordeaux, Imagerie Moléculaire et Thérapies Innovantes en Oncologie (IMOTION), 146 rue Léo Saignat, F33076 Bordeaux.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Grenier
authors.affiliation: Univ. Bordeaux, Imagerie Moléculaire et Thérapies Innovantes en Oncologie (IMOTION), 146 rue Léo Saignat, F33076 Bordeaux.
authors.forename: Franck
authors.initials: F
authors.lastname: Couillaud
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D058948:Cell Tracking; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D043425:Glutamate Carboxypeptidase II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D000954:Antigens, Surface; D005456:Fluorescent Dyes; D057127:Single-Chain Antibodies; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II