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dc.contributor.authorZhang, Hanwen
dc.contributor.authorMoroz, Maxim A
dc.contributor.authorSerganova, Inna
dc.contributor.authorKu, Thomas
dc.contributor.authorHuang, Ruimin
dc.contributor.authorVider, Jelena
dc.contributor.authorMaecke, Helmut R
dc.contributor.authorLarson, Steven M
dc.contributor.authorBlasberg, Ronald
dc.contributor.authorSmith-Jones, Peter M
dc.date.accessioned2017-05-03T16:06:22Z
dc.date.available2017-05-03T16:06:22Z
dc.date.issued2011
dc.date.modified2012-05-13T22:07:59Z
dc.identifier.issn0161-5505
dc.identifier.doi10.2967/jnumed.110.079004
dc.identifier.urihttp://hdl.handle.net/10072/44702
dc.description.abstractThe human somatostatin receptor subtype 2 (hSSTr2)-68Ga-DOTATOC reporter system has several attractive features for potential translation to human studies. These include a low expression of hSSTr2 in most organs, a rapid internalized accumulation of 68Ga-DOTATOC in the SSTr2-expressing cells, and a rapid excretion of unbound radioligand by the renal system. We performed a series of in vitro and in vivo validation studies of this reporter system. METHODS: A retroviral vector containing a dual reporter, pQCXhSSTr2-IRES-GFP (IRES: internal ribosome entry site; GFP: green fluorescent protein), was constructed and transduced into Jurkat, C6, and U87 cells. Stably transduced reporter cells were characterized in vitro using optical and radiometric methods. Multiple tumor-bearing mice were evaluated with 68Ga-DOTATOC PET studies. RESULTS: The dual-reporter genes were incorporated into all tumor cell lines, and their expression levels were confirmed by fluorescence-activated cell sorting (FACS), GFP visualization, and reverse-transcriptase polymerase chain reaction (RT-PCR) analysis for hSSTr2. In vitro, hSSTr2 cell membrane expression was 36,000, 280,000, and 1,250,000 copies per cell for the SSTR2-transfected Jurkat, U87, and C6 cell lines. Small-animal PET of 68Ga-DOTATOC in tumor-bearing mice demonstrated that the in vivo uptake of this radioligand was directly proportional to the in vitro expression of hSSTr2. The in vivo uptake of 68Ga-DOTATOC, at 2 h after injection, was low in all organs except the kidneys (7.8 percentage of injected dose per gram [%ID/g]) and as high as 15.2 %ID/g in transduced C6 tumors. The corresponding transduced-to-nontransduced tumor uptake ratio was 64, and the tumor-to-muscle uptake ratio was around 500. CONCLUSION: 68Ga-DOTATOC is an excellent specific ligand for this hSSTr2 reporter system and for hSSTr2 reporter gene PET. Because DOTATOC has undergone extensive clinical testing, this human reporter system has the potential for translation to human studies.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSociety of Nuclear Medicine
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom123
dc.relation.ispartofpageto131
dc.relation.ispartofissue1
dc.relation.ispartofjournalThe Journal of Nuclear Medicine
dc.relation.ispartofvolume52
dc.rights.retentionY
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchCancer cell biology
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode321101
dc.titleImaging Expression of the Human Somatostatin Receptor Subtype-2 Reporter Gene with 68Ga-DOTATOC
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
gro.date.issued2011
gro.hasfulltextNo Full Text
gro.griffith.authorVider, Jelena


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