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.
Highlights
The prostate specific membrane antigen (PSMA), a type II transmembrane protein produced by the prostatic epithelium, is one of the promising molecular targets for Prostatic carcinoma (PCa) detection[9]
PSMA is expressed in several healthy tissues like the prostatic epithelium, kidney, small intestine and salivary glands, but its expression rate is increased from 100- to 1,000-fold in PCa10
Using these ligands with 68Gallium- or 18Fluor-labeling, there has been a rapid development for PSMA-PET in metastatic or recurrent prostate cancer imaging in several European countries[19]
Summary
The prostate specific membrane antigen (PSMA), a type II transmembrane protein produced by the prostatic epithelium, is one of the promising molecular targets for PCa detection[9]. Several small molecules have been described as ligands to the extracellular domain of PSMA, such as DCFBC or HBED-CC17,18 Using these ligands with 68Gallium- or 18Fluor-labeling, there has been a rapid development for PSMA-PET in metastatic or recurrent prostate cancer imaging in several European countries[19]. Given the limitations of other imaging modalities to identify prostatic carcinoma on a large scale and to guide targeted biopsies, a hybrid approach combining ultrasound and fluorescence could be an attractive solution, as proposed by several groups[24,25,26] Such systems should be able to provide sensitive and specific molecular information through the addition of an optical module to the US systems already used by clinicians and the injection of an optical probe. The probe was evaluated using an orthotopic tumor mouse model and in vivo fluorescence tomography as the imaging method
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