PT  - JOURNAL ARTICLE
AU  - Hanwen Zhang
AU  - Maxim A. Moroz
AU  - Inna Serganova
AU  - Thomas Ku
AU  - Ruimin Huang
AU  - Jelena Vider
AU  - Helmut R. Maecke
AU  - Steven M. Larson
AU  - Ronald Blasberg
AU  - Peter M. Smith-Jones
TI  - Imaging Expression of the Human Somatostatin Receptor Subtype-2 Reporter Gene with <sup>68</sup>Ga-DOTATOC
AID  - 10.2967/jnumed.110.079004
DP  - 2011 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 123--131
VI  - 52
IP  - 1
4099  - http://jnm.snmjournals.org/content/52/1/123.short
4100  - http://jnm.snmjournals.org/content/52/1/123.full
SO  - J Nucl Med2011 Jan 01; 52
AB  - The 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.