Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis

Abstract

Background

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.

Keywords

Neuroendocrine tumors 68Ga-DOTATOC 68Ga-DOTATATE PET

Introduction

Neuroendocrine tumors (NETs) are a diverse group of neoplasms which originate from various cell types of nervous and endocrine systems. Most NETs occur in the gastrointestinal tract or tracheobronchial tree. Embryologically, NETs originate from endocrine cells in the mucosa and submucosa derived from the neural crest, neuorectoderm, and endoderm. NETs comprise 1.5% of all gastrointestinal and pancreatic neoplasms, with an estimated incidence of 1–2 new patients per 100,000 per year (1). The abundant expression of somatostatin receptors (SST) is characteristic of NETs, which can be effectively radiolabeled with somatostatin analogues in vivo (2). To date, five receptor subtypes have been recognized (3). Different expression of SST subtypes related to the tumor type, origin, and extent of differentiation (4).

Nuclear medicine plays an important role in the imaging of NETs. Somatostatin receptor scans (SRS), with 111In, 123I, 99mTc label, are utilized in the diagnosis and staging of NETs (5). Despite the emergence of these radiolabeled somatostatin analogues for scintigraphy, 111In-DTPA-octreotide is the only FDA approved radiopharmaceutical for SRS. However, there are some disadvantages in SRS SPECT scans, such as high physiological uptake negatively impacting the detection of smaller lesions (6). In recent years, with the increasing application of PET imaging, somatostatin analogues have been labeled with different positron emitting isotopes, such as Gallium-68 and Copper-64 in an attempt to utilize PET to image somatostatin receptors (7). Previous studies have demonstrated the value of SRS PET, using 68Ga-DOTANOC, 68Ga-DOTATOC, and 68Ga-DOTATATE, in the diagnosis and staging of NETs. 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE have a high affinity to SST receptor 2, but can bind with varying affinity to the other SST receptor subtypes (8). The in-vitro affinity of 68Ga-DOTATATE in binding the SST subtype 2 (SST2) is approximately 10-fold higher than that of 68Ga-DOTATOC. Because it is the SST2 that is predominantly overexpressed in NETs, this varying affinity may affect the imaging agents’ ability to detect NETs (9). The previous studies reported that 68Ga-DOTANOC, 68Ga-DOTATOC, and 68Ga-DOTATATE PET scan can dramatically improve the spatial resolution compared to SPECT scans (10,11). However, these studies have relative small sample size and limited power for any single study. The purpose of this study was to systematically review and perform a meta-analysis of published data on the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in NET patients.

Material and Methods

Search strategy

A comprehensive computer literature search of the Pubmed, Embase, and Scopus databases was conducted to find relevant published articles on the diagnostic value of 68Ga-DOTATOC and 68Ga-DOTATATE PET in NETs patients. We used a search algorithm that was based on a combination of the terms: (i) “Ga or gallium or 68” and (ii) “NETs” or “NET” or “neuroendocrine” and (iii) “PET” or “position emission tomography” and (iv) DOTATOC or DOTA TOC or DOTA-TOC or DOTA octreocide or DOTATATE or DOTA TATE or DOTA-TATE. No beginning date limitation was used. The terminal date of search was 30 April 2013. The search was limited to English language journals. To maximize the search result, references of the retrieved articles were also scrutinized for additional papers.

Study selection

Papers investigating the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs were eligible for inclusion. The exclusion criteria were: (i) case reports or very small case series; (ii) same patient data (such as duplicate publication); (iii) review articles, editorial, letters, author reply, comments, erratum, conference proceedings; (iv) insufficient data to reassess sensitivity or specificity from individual studies; (v) articles not within the field of our study; (vi) using other radiopharmaceuticals, such as 68Ga-DOTANOC studies. Three researchers (JG, YK, and LL) independently reviewed the titles and abstracts of the retrieved papers, according to the inclusion and exclusion criteria described above. The same three researchers then independently reviewed the full papers to decide their eligibility for inclusion. Different opinion about the papers were resolved in a consensus meeting.

Data extraction from these studies

For every included study, data was collected including basic information (authors, type of NETs, country), patient information, technical information (scanner, tracer injection dosage, time between injection and scan, acquisition protocol, image interpretation, study design, reference standard). Based on these studies, the number of true-positive, true-negative, false-positive, and false-negative findings for 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were recorded on a per-patient-based analysis.

Quality assessment

Three independent reviewers (JG, YK, and LL) evaluated the methodology of the included papers using the quality assessment of diagnostic accuracy studies (QUADAS) criteria (12 –14).

Statistical analysis

Sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs were obtained from individual studies on a per-patient-based analysis. Pooled data were presented with 95% CI. An I-square statistic was also performed to test for heterogeneity between studies (15). The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing patients with NETs. Statistical analyses were performed using Meta-DiSc statistical software version 1.4 (16).

Results

Literature search

The comprehensive computer literature search from Pubmed, Embase, and Scopus databases showed 111 papers. Upon review, 59 papers were excluded: 31 because they were reviews, letters, or editorials, and 28 because they were not within the field of interest of this review. Fifty-two papers were selected and retrieved in full text version. No additional papers were found by screening the references of these articles. After reviewing the full text papers, 42 papers were excluded as case reports, duplicate data, or insufficient data to calculate sensitivity or specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET. Finally, 10 studies, comprising a total sample size of 416 patients with NETs (17 –26), met all inclusion and exclusion criteria and were included in our meta-analysis. The characteristics of the included studies on 68Ga-DOTATOC and 68Ga-DOTATATE PET are presented in Tables 1 and 2.

Table 1.

Basic study, patient characteristics, and technical aspect of 68Ga-DOTATOC in these studies.

Authors	Type of NETs	Country	Ps	Age (years)	Device	Interval time (min)	Dose	Analysis	Study design	Reference
Gabriel et al. (17)	50 GEP, 9 CUP, 6 lung, 19 other	Austria	84	58	PET	100	ND	Visual	Pros	Histology and follow-up
Putzer et al. (18)	35 GEP, 10 CUP, 5 lung, 1 other	Austria	51	ND	PET	60–90	100–120 MBq	Visual	Retro	Histology
Versari et al. (19)	13 GEP, 6 other	Italy	19	56	PET/CT*	60	1.5–2 MBq/Kg	Visual	Retro	Histology and follow-up
Ruf et al. (20)	47 GEP, 5 lung, 9 CUP, 3 other	Germany	64	56	PET/CT*	60	Static	Visual	Retro	Histology and follow-up
Puter et al. (21)	6 GEP, 2 CUP, 7 other	Austria	15	ND	PET	60–90	150 MBq	Visual and Semi	Retro	Histology
Ruf et al. (22)	33 GEP, 4 lung, 14 other	Germany	51	57	PET/CT**	60	100–120 MBq	Visual	Retro	Histology and follow-up

The CT of PET/CT was low dose non-enhanced and non-diagnostic CT.

The CT of PET/CT was diagnostic contrast-enhanced CT.

CUP, carcinoma with unknown primary; GEP, gastroenteropancreatic; ND, no description; Pros, Prospective; NET, neuroendocrine tumor; Retro, Retrospective; Semi, semi-qualitative analysis.

Table 2.

Basic study, patient characteristics, and technical aspect of 68Ga-DOTATATE in these studies.

Authors	Type of NETs	Country	Ps	Age (yyear	Device	Interval time (min)	Dose	Analysis	Study design	Reference
Kayani et al. (23)	28 GEP, 4 CUP, 6 lung	UK	38	53	PET/CT*	45–60	120–200 MBq	Visual and Semi	Retro	Histology and follow-up
Kayani et al. (24)	18 lung	UK	18	56	PET/CT*	45–60	120–200 MBq	Visual and Semi	Retro	Histology and follow-up
Haug et al. (25)	14 GEP 6 lung, 4 CUP, 1 other	Germany	25	57	PET/CT*	60	200 MBq	Visual and Semi	Retro	Histology
Srirajaskanthan et al. (26)	37 GEP, 6 CUP, 2 lung, 2 thymus, 4 other	UK	51	55	PET/CT*	60	120–200 MBq	Visual and Semi	Retro	Histology and follow-up

The CT of PET/CT was low dose non-enhanced and non-diagnostic CT.

CUP, carcinoma with unknown primary; GEP, gastroenteropancreatic; ND, no description; Pros, Prospective; NET, neuroendocrine tumor; Retro, Retrospective; Semi, semi-qualitative analysis.

Quality assessment

Using QUADAS criteria, studies were scored between 7 and 13 with a median score of 11. Thirty percent of studies (3 of 10) scored between 8 and 9. Seventy percent of studies (7 of 10) scored 10 or more. Although none of the studies achieved an A rating, four (40.0%) received a B rating, four (40.0%) received a C rating, and two (20.0%) received a D rating. Overall, the methodological quality of the included studies was medium–high.

Diagnostic performance

The diagnostic performance results of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs in the 10 included studies are presented in Figs. 1 and 2. The sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs, calculated on a per-patient-based analysis, was 93% (95% CI 89–96%) and 96% (95% CI 91–99%), respectively. The included studies were statistically heterogeneous in their estimates of sensitivity on a per-patient-based analysis (I-square: 80.9% and 60.5%) (Fig. 1). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in demonstrating NETs was 85% (95% CI 74–93%) and 100% (95% CI 82–100%), respectively. The included studies of 68Ga-DOTATOC were statistically heterogeneous in their estimates of specificity (I-square: 56.8%) (Fig. 2). However, the included studies of 68Ga-DOTATATE were not statistically heterogeneous in their estimates of specificity (I-square: 0%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98 on a per-patient-based analysis, respectively (Fig. 3).

Fig. 1.

Plot of individual studies and pooled sensitivity of 68Ga-DOTATOC PET and 68Ga-DOTATATE, including 95% confidence intervals (95% CI). The size of circles indicates the weight of each study. The included studies were statistically heterogeneous in their estimates of sensitivity (I-square 80.9% and 60.5%, respectively).

Fig. 2.

Plot of individual studies and pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET, including 95% confidence intervals (95% CI). The size of circles indicates the weight of each study. The included studies were statistically heterogeneous in their estimates of specificity of 68Ga-DOTATOC (I-square 56.8%). The included studies were not statistically heterogeneous in their estimates of specificity of 68Ga-DOTATATE (I-square 0%).

Fig. 3.

Summary ROC curves of diagnostic accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs, including 95% confidence intervals. The area under the ROC curve was 0.96 and 0.98, respectively, demonstrating that 68Ga-DOTATOC and 68Ga-DOTATATE PET are accurate methods in the diagnosis of NETs.

Discussion

To the best of our knowledge, this meta-analysis is the first to individually evaluate the diagnostic performance of 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs. Several single center studies have used 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs. However, many of these studies have limited power and analyzed only small numbers of patients. In order to derive more robust estimates of the diagnostic performance of 68Ga-DOTATOC and 68Ga-DOTATATE PET in patients with NETs, we pooled published studies. A systematic review process was adopted in ascertaining studies, thereby avoiding selection bias. Previous studies have demonstrated the value of PET technology using 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE (27). However, we did not perform the meta-analysis of 68Ga-DOTANOC in this paper because of limited data.

It is crucial to detect the exact location and correct staging of NETs for subsequent patient management. CT, magnetic resonance imaging (MRI), ultrasound, angiography, nuclear medicine techniques, and endoscopy have been used in the diagnosis and staging of NETs. Somatostatin receptor-based radionuclide imaging is the main nuclear medicine method in diagnosing NETs. The mechanism of somatostatin receptor-based radionuclide imaging is the binding of a radiolabeled ligand to the somatostatin receptor. In 1984, Reubi et al. first reported the over expression of somatostatin receptors on tumor tissue (28).

The abundant expression of somatostatin receptor is characteristic of NETs. Up to now, five receptor subtypes have been characterized (from SST1 to SST5). Most tumors express several SST subtypes which are related to the tumor type, origin, and grade of differentiation (4,9). The expression of the various SST subtypes and their density on the tumor cell surface differs among the various tumors with a predominance of SST2 in NETs (29). In 1989, Krenning et al. first reported the scintigraphy of NETs expressing somatostatin receptors using 123I-Tyr-octreotide (30). However, an obvious disadvantage of this compound for scintigraphy was high non-receptor-based accumulation in the liver and intestinal uptake. Subsequently, a radiolabeled somatostatin analogue with 111In was developed and since then, 111In-DTPA-Octreotide has been regarded as the gold standard in nuclear medicine scintigraphy for NETs patients. Previous studies demonstrated that a positive 111In-DTPA-octreotide scan is mainly based on affinity for SST2 (31). Due to higher sensitivity, specificity, and better anatomical delineation of SPECT/CT than planar imaging (32), hybrid SPECT/CT has been used to improve diagnostic accuracy of the 111In-DTPA-Octreotide scan. The overall sensitivity of 111In-DTPA-Octreotide is between 80–100% for carcinoids and 60–90% for pancreatic NETs, mostly depending on tumor type and size (7).

In recent years, PET using 68Gallium labeled somatostatin analogues have been developed rapidly for several reasons. First, PET has become more and more utilized during the last decade. Second, 68Ge/68Ga generators have been developed that produced suitable eluates for labeling. Third, many DOTA-peptides can be labeled with 68Ga. Fourth, the availability of 68Ga PET radiolabeled pharmaceuticals is independent of an on-site cyclotron and therefore less expensive to produce. Lastly, the cost of a 68Ga PET/CT scan is projected to be less than for SRS (33). Up to now, the positron-emitting radionuclide labeled somatostatin analogues have better image quality and spatial resolution compared to γ emitting analogues. The most recent PET/CT scanners provide higher spatial resolution (2–5 mm for clinical scanners) (34). Despite the higher resolution of PET images compared with gamma scintigraphy, these images of PET still lack spatial resolution compared with imaging modalities such as CT and MRI (35).

68Ga-DOTATOC was the first 68Ga labeled somatostatin analogue to be studied in patients. Pooled results of our meta-analysis indicate that 68Ga-DOTATOC and 68Ga-DOTATATE PET demonstrates high sensitivity (93% and 96%, respectively) and good specificity (85% and 100%, respectively). Furthermore, the area under the ROC curve was 0.96 and 0.98, which demonstrated that 68Ga-DOTATOC and 68Ga-DOTATATE PET are accurate methods for the diagnosis of NETs. The 68Ga-DOTATATE PET scan may be better than that of 68Ga-DOTATOC PET scan for the diagnosis of NETs, but definitive comparison requires further studies. Some studies have compared the application of 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE PET in the diagnosis of NETs. Poeppel TD et al. compared the diagnostic role of 68Ga-DOTATATE PET to 68Ga-DOTATOC PET in the same NET patients. 68Ga-DOTATOC and 68Ga-DOTATATE showed a similar diagnostic accuracy in NET lesions, with 68Ga-DOTATOC having a potential advantage. The SUVmax of 68Ga-DOTATOC tended to be higher than those of 68Ga-DOTATATE scan. This study suggested that 68Ga-DOTATOC is preferable for imaging of NET patients (9). Buchmann et al. compared the diagnostic performance of 68Ga-DOTATOC PET and 111In-DTPAOC SPECT in the NETs. Twenty-seven NETs patients were prospectively examined. This study concluded that 68Ga-DOTATOC was superior to 111In-DTPAOC SPECT in the diagnosis of NETs in the lung and skeletal systems and similar for the diagnosis of NETs in the liver and brain. Therefore, 68Ga-DOTATOC can guide clinical management (6).

Reubi et al. reported that the affinity of 68Ga-DOTATATE in binding SST2 to be approximately 10-fold higher than that of 68Ga-DOTATOC (36). But this approximately 10-fold higher affinity for the SST2 of 68Ga-DOTATATE has not been proven to be clinically relevant (9). Wild D et al. compared 68Ga-DOTANOC and 68Ga-DOTATATE PET in NETs. This study concluded that the SST2-, 3-, 5-specific radiotracer 68Ga-DOTANOC detected significantly more lesions than the SST2-specific radiotracer 68Ga-DOTATATE in gastroenteropancreatic neuroendocrine tumors (37). 68Ga-DOTANOC can bind with a broader range of somatostatin subtype receptors, including SST2, SST3, and SST5 (10). In fact, 68Ga-DOTANOC had a wider receptor binding ability than that of 68Ga-DOTATATE, which is SST2-specific. Antunes et al. reported that 68Ga-DOTANOC located more metastases than that of SST2-specific tracers (8). This study also demonstrated 68Ga-based tracers, such as 68Ga-DOTANOC, had higher binding affinities to SST2 and SST5 than lutetium and indium derivatives (8). Kabasakal et al. also compared the role of 68Ga-DOTANOC and 68Ga-DOTATATE in the diagnosis of NETs in the same patient. This study demonstrated that the SUVmax of 68Ga-DOTATATE was significantly higher than that of 68Ga-DOTANOC and the number of lesions shown by 68Ga-DOTATATE was higher than that of 68Ga-DOTANOC (38).

Another advantage of 68Ga-DOTATOC and 68Ga-DOTATATE PET scan is that the patient does not have to come back for scanning the next day. Oberg K et al. commented that somatostatin receptor PET using 68Ga labeled somatostatin analogues was the most comprehensive diagnostic molecular imaging method for NETs (39).

The included studies of 68Ga-DOTATOC were statistically heterogeneous in their estimates of specificity (I-square: 56.8%). This heterogeneity is likely due to the diversity in the methodological design between different studies (Table 1). For example, some authors used PET as the scanner, while some authors used PET/CT as the scanner. The attenuation correction of PET is completed by 68Ge, while that of PET/CT is completed by CT. The CT of PET/CT of some studies is low dose non-enhanced and non-diagnostic CT, just for attenuation correction. Souvatzoglou et al. compared the SUV from PET/attenuation correction CT intraindividually in various organs and tumor lesion with SUV from alone PET. This study demonstrated that there was a significant correlation between the SUVs using stand-alone PET and PET/CT. Owing to the additional accurate anatomical information provided by the CT component of PET/CT, PET/CT had a more important value in the diagnosis and evaluation of therapy response due to functional and morphological information of the disease (40). Despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended (20). The sensitivity and specificity of PET/CT are higher than those of PET. The CT of PET/CT in some study was diagnostic contrast-enhanced CT (22). Seemann et al. assessed PET, CT, and PET/CT in the detection of metastases from gastrointestinal NETs. This study concluded that the PET/CT of combination of molecular/metabolic with anatomical/morphological information improved the diagnostic accuracy for the detection of metastases in comparison to any single PET or CT. Low dose CT cannot replace venous dominant contrast-enhanced CT in the detection of liver and lymph node metastases, but was equal in the detection of osseous metastases and identifying of pulmonary lesions (41). Ruf et al. assessed the value of the single CT phases of a triple-phase (early arterial, portal-venous inflow, and venous) CT protocol compared with 68Ga-DOTATOC PET/CT. This study concluded that no CT phase can be omitted in NET imaging, and the triple-phase protocol continued to be strongly recommend for PET/CT (22). Versari et al. compared the role of Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT (MDCT) in the diagnosis of duodenopancreatic NETs. On a lesion basis, PET and MDCT identified correctly as NETs 20/23 (87%) and 13/18 (72%) lesions. MDCT detected fewer lesions (in particular fewer small lesions) than EUS and PET in this study, but the difference was not significant. This study concluded that despite the comparable accuracy of the EUS, MDCT, and PET/CT, their combination allowed the detection of the highest number of suspected lesions (19). On the other hand, we conducted pooled sensitivity and specificity on a per-patient-based analysis, instead of per-lesion-based analysis or a per-region-based analysis. The interval time between injection and scanning may also contribute the heterogeneity. The interpretation of PET/CT of in some clinical center was interpreted by nuclear medicine physicians, while the images of PET and CT of PET/CT of some other clinical center was read by nuclear medicine physicians and radiologists, respectively. Nanni et al. reported that the execution of PET/contrast-enhanced CT in the same session increased the quality of the final report by nuclear physician and radiologist and provided clear diagnostic information to the clinician (42). The CT of PET/CT in one study of the meta-analysis was contrast-enhanced CT (22). However, the author did not describe clearly nuclear medicine physician or radiologist read the images of PET/CT. The baseline differences among the patients in the included study (Table 1) may also contribute to the observed heterogeneity of the results. However, there was not sufficient data to obtain significant results performing 68Ga-DOTANOC PET analysis in the diagnosis of NETs. However, the included studies of 68Ga-DOTATATE were not statistically heterogeneous in their estimates of specificity (I-square: 0%). The lack of heterogeneity of 68Ga-DOTATATE may be related to similar methodological design between different studies (Table 2). For example, all studies related to 68Ga-DOTATATE used PET/CT. Three of the four 68Ga-DOTATATE studies were performed in UK. On the other hand, all of the studies included in the review were shown to be of moderate quality according to QUADAS. In our study, none of these papers got an A rating, and six studies (60%) had the lowest rating of C or D. A major disadvantage of the QUADAS is that it does not take into account the sample size which has an obvious relationship with the precision of study and its effectiveness.

Finally, based on high sensitivity and good specificity, 68Ga-DOTATOC and 68Ga-DOTATATE PET may be considered good examinations in the diagnostic workup of NETs. Although the literature about the use of 68Ga-DOTATOC and 68Ga-DOTATATE PET in NETs remains limited, further large sample size and multicenter studies will be necessary to evaluate the diagnostic performance of 68Ga-DOTATOC and 68Ga-DOTATATE PET in NETs.

In conclusion, 68Ga-DOTATOC and 68Ga-DOTATATE PET are accurate methods to diagnose NETs with high sensitivity and specificity. The 68Ga-DOTATATE PET scan may be better than the 68Ga-DOTATOC PET scan in the diagnosis of NETs but a large-scale, prospective, and direct comparison of 68Ga-DOTATOC and 68Ga-DOTATATE is needed.

Footnotes

Funding

Jigang Yang was partially supported by Natural Science Foundation of China (No. 81101069), Beijing Natural Science Foundation (No. 7112035), and Beijing Science and Technology New Star Plan (No. 0051).

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