PMID- 29930736
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20190827
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 8
IP  - 12
DP  - 2018
TI  - Somatostatin receptor type 2 as a radiotheranostic PET reporter gene for 
      oncologic interventions.
PG  - 3380-3391
LID - 10.7150/thno.24017 [doi]
AB  - Reporter gene systems can serve as therapy targets. However, the therapeutic use 
      of reporters has been limited by the challenges of transgene delivery to a 
      majority of cancer cells. This study specifically assesses the efficacy of 
      targeting human somatostatin receptor subtype 2 (hSSTR2) with peptide receptor 
      radionuclide therapy (PRRT) when a small subpopulation of cells bears the 
      transgene. Methods: The hSSTR2 transgene was delivered to A549 and Panc-1tumors 
      using the lentiviral vector, LV-hSSTR2-IRES-GFP or murine mesenchymal stem cells 
      (mMSC)s using a retroviral vector. SSTR2 expression was assessed using Western 
      blot and correlated to GFP fluorescence and (68)Ga-DOTATOC uptake. Wild type 
      (WT), transduced (TD), and mixed population A549 or Panc-1 xenografts were 
      implanted in nude mice. Separate groups with A549(WT) and Panc-1(WT) tumors 
      received intratumoral injection of SSTR2-expressing mMSCs. Tumor-bearing mice 
      were treated with (90)Y-DOTATOC or saline and evaluated with (68)Ga-DOTATOC PET 
      before and after treatment. Results: Cell studies showed a strong correlation 
      between (68)Ga-DOTATOC uptake and SSTR2 expression in A549 (p < 0.004) and Panc-1 
      cells (p < 0.01). (68)Ga-DOTATOC PET SUVmean was 8- and 5-fold higher in TD 
      compared to WT A549 and Panc-1 tumors, respectively (p < 0.001). After 
      (90)Y-DOTATOC treatment, 100% TD and mixed population TD xenografts showed growth 
      cessation while the WT xenografts did not. A549(WT) and Panc-1(WT) tumors with 
      SSTR2-expressing mMSCs treated with (90)Y-DOTATOC showed significantly lower 
      tumor volumes compared to controls (p < 0.05). (68)Ga-DOTATOC PET SUVmean of 
      treated TD tumors monotonically declined and was significantly lower than that of 
      non-treated xenografts. Conclusions: We showed that SSTR2 delivery to a small 
      population of cells in tumor in conjunction with PRRT is effective in tumor 
      growth cessation. The availability of various transgene delivery methods for 
      hSSTR2 and radiotherpaeutic somatostatin analogs highlights the direct 
      translational potential of this paradigm in the treatment of various cancers.
FAU - Heidari, Pedram
AU  - Heidari P
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
FAU - Kunawudhi, Anchisa
AU  - Kunawudhi A
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
FAU - Martinez-Quintanilla, Jordi
AU  - Martinez-Quintanilla J
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
FAU - Szretter, Alicia
AU  - Szretter A
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
FAU - Shah, Khalid
AU  - Shah K
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
FAU - Mahmood, Umar
AU  - Mahmood U
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA.
LA  - eng
GR  - R01 CA166582/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180523
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Receptors, Somatostatin)
RN  - ABF7OG3FA3 (90Y-octreotide, DOTA-Tyr(3)-)
RN  - D73QL0OMU2 (somatostatin receptor 2)
RN  - RWM8CCW8GP (Octreotide)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage
MH  - Biomarkers, Tumor/*analysis
MH  - Disease Models, Animal
MH  - Genes, Reporter
MH  - Heterografts
MH  - Humans
MH  - Mesenchymal Stem Cells
MH  - Mice, Nude
MH  - Molecular Targeted Therapy/*methods
MH  - Neoplasm Transplantation
MH  - Octreotide/administration & dosage/analogs & derivatives
MH  - Pancreatic Neoplasms/*diagnosis/*drug therapy
MH  - Positron-Emission Tomography/*methods
MH  - Radiopharmaceuticals/administration & dosage
MH  - Receptors, Somatostatin/*metabolism
MH  - Theranostic Nanomedicine/*methods
MH  - Treatment Outcome
PMC - PMC6010996
OTO - NOTNLM
OT  - 68Ga-DOTATOC
OT  - peptide receptor radionuclide therapy (PRRT)
OT  - reporter gene
OT  - somatostatin receptor
OT  - theranostic
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2018/06/23 06:00
MHDA- 2019/08/28 06:00
PMCR- 2018/01/01
CRDT- 2018/06/23 06:00
PHST- 2017/11/25 00:00 [received]
PHST- 2018/04/08 00:00 [accepted]
PHST- 2018/06/23 06:00 [entrez]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - thnov08p3380 [pii]
AID - 10.7150/thno.24017 [doi]
PST - epublish
SO  - Theranostics. 2018 May 23;8(12):3380-3391. doi: 10.7150/thno.24017. eCollection 
      2018.