Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors.
Purpose
To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs.
Material and Methods
A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs.
Results
Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89–96%) and 96% (95% CI 91–99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74–93%) and 100% (95% CI 82–100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis.
Conclusion
The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.
HellerMTShahAB. Imaging of neuroendocrine tumors. Radiol Clin North Am2011; 49: 529–548.
2.
ChitiAFantiSSavelliG. Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours. Eur J Nucl Med1998; 25: 1396–1403.
3.
HoyerDBellGIBerelowitzM. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci1995; 16: 86–88.
4.
ReubiJCWaserB. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging2003; 30: 781–793.
5.
KrenningEPKwekkeboomDJBakkerWH. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med1993; 20: 716–731.
6.
BuchmannIHenzeMEngelbrechtS. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging2007; 34: 1617–1626.
7.
TeunissenJJKwekkeboomDJValkemaR. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer2011; 18(Suppl. 1): S27–S51.
8.
AntunesPGinjMZhangH. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?Eur J Nucl Med Mol Imaging2007; 34: 982–993.
9.
PoeppelTDBinseIPetersennS. 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med2011; 52: 1864–1870.
10.
WildDSchmittJSGinjM. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging2003; 30: 1338–1347.
11.
AmbrosiniVCampanaDBodeiL. 68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors. J Nucl Med2010; 51: 669–673.
12.
YangJHaoRZhuX. Diagnostic role of 18F-dihydroxyphenylalanine positron emission tomography in patients with congenital hyperinsulinism: a meta-analysis. Nucl Med Commun2013; 34: 347–353.
13.
HaoRYuanLKanY. Diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin: a meta-analysis. Nucl Med Commun2013; 34: 682–688.
14.
Van den BruelAThompsonMJHaj-HassanT. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ2011; 342: d3082–d3082.
15.
HigginsJPThompsonSGDeeksJJ. Measuring inconsistency in meta-analyses. BMJ2003; 327: 557–560.
16.
ZamoraJAbrairaVMurielA. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol2006; 6: 31–31.
17.
GabrielMDecristoforoCKendlerD. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med2007; 48: 508–518.
18.
PutzerDGabrielMHenningerB. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med2009; 50: 1214–1221.
19.
VersariACamelliniLCarlinfanteG. Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study. Clin Nucl Med2010; 35: 321–328.
20.
RufJHeuckFSchieferJ. Impact of multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors. Neuroendocrinology2010; 91: 101–109.
21.
PutzerDGabrielMKendlerD. Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients. Q J Nucl Med Mol Imaging2010; 54: 68–75.
22.
RufJSchieferJFurthC. 68Ga-DOTATOC PET/CT of neuroendocrine tumors: spotlight on the CT phases of a triple-phase protocol. J Nucl Med2011; 52: 697–704.
23.
KayaniIBomanjiJBGrovesA. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer2008; 112: 2447–2455.
24.
KayaniIConryBGGrovesAM. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med2009; 50: 1927–1932.
25.
HaugAAuernhammerCJWanglerB. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging2009; 36: 765–770.
26.
SrirajaskanthanRKayaniIQuigleyAM. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy. J Nucl Med2010; 51: 875–882.
27.
VirgoliniIAmbrosiniVBomanjiJB. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging2010; 37: 2004–2010.
28.
ReubiJCLandoltAM. High density of somatostatin receptors in pituitary tumors from acromegalic patients. J Clin Endocrinol Metab1984; 59: 1148–1151.
29.
ReubiJCWaserBSchaerJC. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med2001; 28: 836–846.
30.
KrenningEPBakkerWHBreemanWA. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet1989; 1: 242–244.
31.
HoflandLJLambertsSWvan HagenPM. Crucial role for somatostatin receptor subtype 2 in determining the uptake of [111In-DTPA-D-Phe1]octreotide in somatostatin receptor-positive organs. J Nucl Med2003; 44: 1315–1321.
32.
ZhenLLiHLiuX. The application of SPECT/CT for preoperative planning in patients with secondary hyperparathyroidism. Nucl Med Commun2013; 34: 439–444.
33.
BreemanWAde BloisESze ChanH. 68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives. Semin Nucl Med2011; 41: 314–321.
34.
BrayMDi MascioMde Kok-MercadoF. Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes. Antiviral Res2010; 88: 129–142.
35.
HistedSNLindenbergMLMenaE. Review of functional/anatomical imaging in oncology. Nucl Med Commun2012; 33: 349–361.
36.
ReubiJCScharJCWaserB. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med2000; 27: 273–282.
37.
WildDBomanjiJBBenkertP. Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors. J Nucl Med2013; 54: 364–372.
38.
KabasakalLDemirciEOcakM. Comparison of (6)(8)Ga-DOTATATE and (6)(8)Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours. Eur J Nucl Med Mol Imaging2012; 39: 1271–1277.
39.
ObergK. Gallium-68 somatostatin receptor PET/CT: Is it time to replace (111)Indium DTPA octreotide for patients with neuroendocrine tumors?Endocrine2012; 42: 3–4.
40.
SouvatzoglouMZieglerSIMartinezMJ. Standardised uptake values from PET/CT images: comparison with conventional attenuation-corrected PET. Eur J Nucl Med Mol Imaging2007; 34: 405–412.
41.
SeemannMD. Detection of metastases from gastrointestinal neuroendocrine tumors: prospective comparison of 18F-TOCA PET, triple-phase CT, and PET/CT. Technol Cancer Res Treat2007; 6: 213–220.
42.
NanniCZompatoriMAmbrosiniV. The additional diagnostic value of contemporary evaluation of FDG PET/CT scan and contrast enhanced CT imaging both acquired by a last generation PET/CT system in oncologic patients. Biomed Pharmacother2013; 67: 172–178.
