title: Noninvasive repetitive imaging of somatostatin receptor 2 gene transfer with positron emission tomography.
abstract: Noninvasive in vivo imaging of gene expression is desirable to monitor gene transfer in both animal models and humans. Reporter transgenes with low endogenous expression levels are instrumental to this end. The human somatostatin receptor 2 (hSSTR2) has low expression levels in a variety of tissues, including muscle and liver. We tested the possibility of noninvasively and quantitatively monitoring hSSTR2 transgene expression, following adeno-associated viral (AAV) vector-mediated gene delivery to murine muscle and liver by positron emission tomography (PET) using (68)gallium-DOTA-Tyr(3)-Thr(8)-octreotate ((68)Ga-DOTATATE) as a highly specific SSTR2 ligand. Repetitive PET imaging showed hSSTR2 signal up to 6 months, which corresponds to the last time point of the analysis, after gene delivery in both transduced tissues. The levels of tracer accumulation measured in muscle and liver after gene delivery were significantly higher than in control tissues and correlated with the doses of AAV vector administered. As repetitive, quantitative, noninvasive imaging of AAV-mediated SSTR2 gene transfer to muscle and liver is feasible and efficient using PET, we propose this system to monitor the expression of therapeutic genes coexpressed with SSTR2.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cotugno
authors.forename: Michela
authors.initials: M
authors.lastname: Aurilio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Annunziata
authors.forename: Anita
authors.initials: A
authors.lastname: Capalbo
authors.forename: Armida
authors.initials: A
authors.lastname: Faella
authors.forename: Valentina
authors.initials: V
authors.lastname: Rinaldi
authors.forename: Caterina
authors.initials: C
authors.lastname: Strisciuglio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Tommaso
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloj
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D049268:Positron-Emission Tomography / Q000379:methods*; D017481:Receptors, Somatostatin / Q000235:genetics*; D019076:Transgenes
chemical_list: D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2
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