In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe

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.

Scientific reports. 2016 Mar 21*** epublish ***

Claire Mazzocco, Giulio Fracasso, Coralie Germain-Genevois, Nathalie Dugot-Senant, Mariangela Figini, Marco Colombatti, Nicolas Grenier, Franck Couillaud

CNRS UMS 3428 and Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux., Department of Medicine, Verona University, Italy., CNRS UMS 3428 and Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux., Service d'Histologie INSERM US005, Univ. Bordeaux, 146 rue Léo Saignat, F33076 Bordeaux., Molecular Therapies Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, Milano, Italy., Department of Medicine, Verona University, Italy., 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.