Diagnostic Applications of Nuclear Medicine: Colorectal Cancer
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Colorectal cancer is the fourth most common neoplastic disease (50–60% overall survival at 5 years); 90–95% of colorectal cancers are adenocarcinoma. Important prognostic factors include: whether the tumor is well differentiated, the extent of the primary tumor, and the presence of local and/or lymph node invasion. Two staging classifications for colorectal cancer are available: Dukes’ classification and the TNM stage system by the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC).
Contrast-enhanced computed tomography (CECT) of the chest, abdomen, and pelvis is used in pretreatment staging. Because of the high incidence of disease recurrence (30–40%), morphological imaging (CT, abdominal ultrasound) and serial measurements of serum markers (carcinoembryonic antigen, or CEA) are used in the follow-up. The use of [18F]FDG-PET for early detection of primary colorectal cancer is limited due to the low sensitivity for small tumors as well as for mucinous lesions. False-positive PET findings are also reported in patients with inflammatory bowel disease (IBD) or previous diagnostic polipectomy. Although [18F]FDG PET is more sensitive than CT in detecting regional lymph node involvement, CT is better at detecting liver metastases. As a result, the role of [18F]FDG PET-CT for presurgical staging is unclear. [18F]FDG-PET is useful as a complementary exam in selected patients with a high metastatic potential.
During restaging and follow-up, whole-body [18F]FDG-PET/CT is recommended to localize recurrent disease in cases of elevated serum CEA and negative morphological imaging findings or indeterminate lesions. Combined PET/CT tomography improves the accuracy of the evaluation of colorectal cancer, especially in the visualization of abdomino-pelvic extrahepatic disease.
[18F]FDG-PET may be useful to evaluate response to chemotherapy, although the optimum timing of the assessment of metabolic response remains unsettled. Moreover, new drugs targeted to angiogenesis or tyrosine kinase have opened new frontiers to the use of [18F]FDG-PET in evaluating response because of their cytostatic rather than cytoreductive effect. In rectal cancer it is often difficult to evaluate response to radiotherapy by anatomic imaging due to residual tissue mass, but [18F]FDG-PET/CT can detect residual tumor by the metabolic activity. Finally, [18F]FDG-PET has been proposed in the evaluation of response to local treatment of liver and lung metastases by radiofrequency ablation (RFA). In patients with unresectable liver metastases and/or advanced burden of liver disease, transarterial radioembolization with microspheres labeled with 90Y is becoming a valid therapeutic alternative to chemoembolization and RFA.
KeywordsColorectal cancer [18F]FDG-PET/CT in colorectal cancer Diagnostic imaging in colorectal cancer Staging and follow-up in colorectal cancer Assessment of response to therapy in colorecatl cancer Trans-arterial radioembolization with 90Y-microspheres for liver metastases from colorecxtal cancer
American Joint Committee on Cancer
Best overall metabolic response
Contrast-enhanced computed tomography
Complete metabolic response
X-ray computed tomography
European Organization for Research and Treatment of Cancer
Inflammatory bowel disease
Metastasis status according to the AJCC/UICC TNM staging system
Magnetic resonance imaging
Lymph node status according to the AJCC/UICC TNM staging system
Negative predictive value
Positron emission tomography response criteria in solid tumors
Positron emission tomography
Positron emission tomography/computed tomography
Positron emission tomography/magnetic resonance imaging
Progressive metabolic disease
Partial metabolic response
Positive predictive value
PET residual disease in solid tumor
Radiotherapy planning target volume
Response evaluation criteria in solid tumors
Region of interest
Stable metabolic disease
Standardized uptake value
Tumor status according to the AJCC/UICC TNM staging system
Total lesion glycolysis
Tumor regression grade
Union Internationale Contre le Cancer (International Union Against Cancer)
Overview of Colon-Rectal Cancer: Incidence and Mortality
Colorectal cancer is the fourth most common neoplastic disease, after prostate, lung, and breast cancer, and the second leading cause of death from cancer, with an estimated overall survival at 5 years of 50–60% in Western countries [1, 2]. There is considerable evidence for its correlation with saturated fat, low-fiber diet, obesity, and inflammatory bowel disease (IBD), as well as with genetic factors (familial adenomatous polyposis or the Lynch syndrome). Mortality rates have steadily decreased, particularly between 1980 and 2005, owing to improved surgical and adjuvant therapies (chemotherapy protocols and targeted molecular treatment) and more extensive screening programs with early diagnosis .
Despite improved prognosis and extensive primary and secondary prevention programs, about 150,000 new cases of colorectal cancer have been diagnosed in 2009 in the United States alone. Colorectal cancer remains a huge health problem .
Some studies suggest a poorer prognosis in symptomatic patients due to local complications (e.g., locally extended cancer with obstruction and perforation) at diagnosis. Among patient characteristics, age less than 40 years at diagnosis is another factor of poor prognosis, because cancer is more aggressive in younger patients, with a high percentage of positive lymph nodes and aggressive histological features. As to histology, adenocarcinoma accounts for 90–95% of colorectal cancers. These tumors are classified into three groups according to the Dukes’ grading system : grade 1, the most differentiated forms; grade 2, the intermediate forms; and grade 3, the less differentiated forms. The less differentiated forms carry a worse prognosis as they are locally more extensive, with a higher lymphatic affinity and metastatic potential. The remaining 5–10% of colorectal cancers include other histological variants such as colloid or mucinous adenocarcinomas, less frequently squamous cells, undifferentiated carcinomas, and carcinoid forms which usually arise in the rectum. The mucinous variant is also correlated with a more aggressive behavior and frequently with an advanced stage at diagnosis. Primary tumor extension at diagnosis expressed by local invasion and number of positive lymph nodes seems to be the most important prognostic factor, as curative treatment is possible only at the early stage of disease. Nearly 40% of patients present with a confined primary tumor at diagnosis, almost 40% with locally advanced disease, and the remaining 20% with metastatic spread. A localized tumor means that it is limited to the bowel wall, without lymphatic spread or peritoneal seeding when considering intraperitoneal sites (cecum, transverse colon, and sigmoid) or without extension to retroperitoneal lymph nodes, or to retroperitoneal tissue such as the kidneys, or to the ureter or the pelvis when considering extraperitoneal sites (ascending and descending colon and the majority of rectal localizations). Lymphatic spread usually occurs via the paracolic lymph node groups by the mesenteric the retroperitoneal lymph nodes in extraperitoneal localizations of colon cancer, and the perirectal lymph nodes in rectal cancer. Metastatic spread is often localized to the liver in colon cancer and in tumors of the upper rectum, whose venous system drains into the portal circulation. The distal rectum has a double drainage: to the portal system via the inferior mesenteric vein through the superior hemorrhoidal veins with metastatic spread to the liver, and to the inferior vena cava via the pelvic veins through the middle and inferior hemorrhoidal plexus; in the latter case case, lung metastases are more frequent. Bone lesions can be caused by metastatic spread through the vertebral venous plexus and are more frequently located in the sacrum, coccyx, pelvis, and lumbar vertebrae.
Staging Classification and Prognosis
There are two different surgical staging classifications for colorectal cancer. Dukes’ classification is a practical system that classifies tumors into three groups according to the extent of bowel wall penetration: (A) penetration into but not through the bowel wall, (B) penetration through the bowel wall, and (C) lymph node involvement regardless of bowel wall penetration. Stage D was later added to indicate disease extension beyond the limit of surgical resection and includes metastatic tumor. This system correlates easily with different prognoses for different stages. A 1984 meta-analysis by the Large Bowel Project, London, identified the number of positive lymph nodes as the most important factor . A recent study by Fretwell et al. on 351 patients confirmed this result, showing that lymph node status is an independent prognostic factor .
AJCC/UICC staging classification for colorectal cancer according to the TNM system
Tis, N0, M0
T3, N0, M0
T4, N0, M0
T1-T2, N1, M0
T3-T4, N1, M0
Any T, N2, M0
Any T, any N, M1
Prognosis based on AJCC staging classification of colon and rectal cancer released by American Cancer Society (results from study of National Cancer Institute’s SEER database on 120,000 people diagnosed with colon cancer between 1991 and 2000)
5-year survival rate (%)
5-year survival rate (%)
Clinical Objectives in Colorectal Cancer
The first objective in managing colorectal cancer patients is adequate and complete preoperative staging, which is routinely done by abdominal and thoracic contrast-enhanced computed tomography (CECT) to evaluate overall liver status. The purpose of primary tumor treatment is to be as curative and radical as possible, while exactly defining local disease extension. This is also important in cases with isolated metastatic spread. Surgery is usually the first choice treatment for localized disease and single and/or resectable metastases. In locally advanced disease, the use of neoadjuvant chemoradiation therapy appears to improve prognosis [19, 20]. Adjuvant treatment is indicated to limit tumor recurrence, based on initial tumor extension and prognostic factors (Stage III, lymph node metastases, poorly differentiated tumors, lymphovascular invasion). It ordinarily consists of systemic chemotherapy protocols based on 5-fluorouracil as first choice. On completion of treatment, close follow-up is essential because of the high percentage of disease recurrence after primary treatment (30–40%) . Follow-up entails systematic evaluation by morphological imaging techniques (CT, abdominal ultrasounds) and systemic evaluation of serum markers (carcinoembryonic antigen, or CEA) to detect relapse or metastatic spread. Recurrence can be local, regional (lymph node localizations), peritoneal seeding, or metastatic liver/lung lesions, and it is closely correlated with primary tumor characteristics. The recurrence rate in locally advanced tumors is about 20% and rises to around 50% in the presence of initial lymph node involvement.
Current Role of Nuclear Medicine
Of the nuclear imaging modalities for managing patients with colorectal cancer, PET/CT with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most widely used. It is considered the most useful technique for achieving clinical objectives and has been added to standard imaging techniques as a new “strategic” tool in this scenario.
Several studies have demonstrated that whole-body [18F]FDG-PET is an accurate noninvasive technique in staging/restaging several types of malignancies, and its usefulness has also been proved in the management of patients with colorectal cancer [22, 23, 24]. [18F]FDG-PET is recognized as appropriate in restaging patients with suspected recurrence of colorectal cancer, elevated serum tumor markers such as CEA, and a negative or inconclusive standard diagnostic workup and in presurgical evaluation of patients with recurrence of disease and potentially resectable metastatic lesions.
In the preoperative initial staging of disease, [18F]FDG-PET is considered potentially useful but not yet sufficiently demonstrated .
Finally, [18F]FDG-PET in colorectal cancer holds promise for systematic follow-up and evaluation of response to therapy, especially in the evaluation of chemoradiation therapy in metastatic cancer (late and early response) or of local treatment efficacy such as radiofrequency ablation of liver metastases. Furthermore, because positivity and intensity of [18F]FDG uptake are an expression of tumor aggressiveness, [18F]FDG-PET is also considered as a prognostic tool .
Classic, standard nuclear imaging techniques such as 99mTc-HDP bone scan in disease staging and restaging are limited to the evaluation of secondary bone lesions. Finally, nuclear techniques such as treatment with intra-arterial 90Y-microspheres for unresectable liver metastases are becoming increasingly available.
The current and potential uses of nuclear medicine techniques will be discussed in the following paragraphs.
Presurgical Staging of Primary Colorectal Cancer
Because few studies on a small number of patients are currently available, the role of [18F]FDG-PET in the presurgical staging of primary disease remains controversial. Primary cancer is detected and studied by morphological imaging, oral contrast CT, and endo-ultrasonography which also allows for biopsy and histological confirmation [27, 28].
Several studies reported a high sensitivity of [18F]FDG-PET (95–100%) in detecting the primary tumor, even when in situ [29, 30, 31]. The tumor’s histopathological features and lesion diameter are closely correlated with these data. False-negative results have been reported in cases of mucinous carcinoma and of small tumor foci in tubulovillous polyps or villous adenoma [29, 30, 32]. Abdel-Nabi et al. reported false-positive PET findings (positive predictive value [PPV] 90%) in patients without colorectal cancer but with IBD or previous diagnostic polypectomy . Although [18F]FDG-PET appears to be more useful in detecting regional lymph node involvement and liver metastases, conflicting results have been reported. Abdel-Nabi and Kantorova both found higher sensitivity (78–88%) with PET than with contrast-enhanced abdominal/pelvic CT (38–67%) or ultrasonography (25%), with high specificity (96–100%) in detecting liver metastases [29, 30]. Furukawa reported that, when compared with multidetector helical CT for routine staging, [18F]FDG-PET did not seem superior in terms of sensitivity and accuracy . In this study, [18F]FDG-PET accuracy in detecting lymph node involvement did not show a statistical difference in comparison with CECT accuracy (59% vs. 62%). Patel et al. in a systematic review reported that for extrahepatic lesions (three studies, 178 patients), PET/CT was more sensitive than CT, while specificity was similar (PET/CT sensitivity [SN] = 75–89% and specificity [SP] = 95–96% vs. CT SN = 58–64% and SP = 87–97%). For hepatic lesions (five studies; 316 patients), PET/CT had higher SN and SP than CT (PET/CT SN = 91–100% and SP = 75–100%; CT SN = 78–94% and SP = 25–98% .
Other studies confirmed low PET sensitivity (around 30%) primarily due to false-negative findings in cases of micrometastases or the presence of metastatic lymph nodes adjacent to the primary tumor . In a review by Vriens et al., other more recent studies on a small group of patients showed that [18F]FDG-PET can change patient management in 12–27% of cases when added to CT and/or pelvic magnetic resonance imaging (MRI) and ultrasonography, leading the bulk of cases to cancelation of surgery after unexpected metastatic lesions were detected, or to extension of the surgical plan or the radiotherapy field, or to neoadjuvant treatment after detection of pathological lymphadenopathy missed at morphological imaging [35, 36, 37, 38, 39, 40].
In brief, the weighted mean change in the management of colorectal cancer calculated in the review was about 10.7% (95% confidence interval [CI] 7.6–14.5%) . The discordant findings among the different studies can be explained by the patient selection bias, which showed a major impact of [18F]FDG-PET in patients with a high metastatic potential, while in localized disease [18F]FDG-PET added less additional information to the standard diagnostic workup (contrast-enhanced CT and colonoscopy).
What can be said at present is that the use of PET in staging primary colorectal cancer can lead to a change in clinical management when compared to standard diagnostic workup, but its systematic use in this application is not yet recognized.
We evaluated the role of [18F]FDG-PET/CT in preoperative staging of rectal carcinoma and compared it to the conventional imaging techniques. With the collaboration of two PET centers and a total of four PET/CT scanners, 141 patients with diagnosis of rectal adenocarcinoma were studied from October 2006 to November 2014. For the evaluation of N stage, in 92/141 cases we found correlation between PET and conventional imaging: 47/92 cases with evidence of lymph node metastases (N+) and 45/92 without evidence of lymph node metastases (N−). In the remaining 49 cases, PET and conventional imaging were discordant: in 38/49 PET did not identify small “mesorectal” lymph nodes (38/49); in 11 cases PET showed some “pelvic” unexpected lymph node metastases. In the M staging, in 106/141 patients (75%) we found correlation between PET and conventional imaging, with the same final stage of disease: in 46/106 patients without evidence of distant metastases (M−) and in 60/106 with evidence of distant metastases (liver, lung, skeletal, peritoneal, adrenal). In the remaining 35/141 patients (25%), there was discordance between PET and conventional imaging in the M stage: in 9/35 cases PET identified unexpected metastases (three skeletal and six liver and/or lung; out of these we had one false positive case in the lung). In the remaining 26/35 patients, PET excluded distant metastases to the liver, spleen, and lung (out of these we had three lung false-negative findings and two liver false-negative findings). PET also identified seven cases of synchronous neoplasia (five in the colon, one gastric, and one thymoma). So, in our study PET showed high false-negative rate in the locoregional lymph nodes staging due to the spatial resolution limitations, but increased accuracy in the identification of lymph node metastases in less common areas; PET has also provided additional and/or complementary information regarding distant metastases; finally, PET identified unexpected neoplasia in 4% of patients. Considering the different and complementary information derived from PET and conventional imaging, at the moment we suggest the use of both techniques for rectal cancer staging [42, 43].
Recurrent Colorectal Cancer
In this subset of patients, [18F]FDG-PET should be considered as an essential tool for better clinical management. Given its high NPV (around 95%), when a PET scan in this patient subgroup is negative, the presence of detectable disease recurrence could be excluded with [18F]FDG-PET, though close clinical follow-up should still be undertaken. While there is considerable evidence for the usefulness of [18F]FDG-PET, certain limitations to the technique deserve mention. [18F]FDG-PET can produce false-positive findings at evaluation of abdominal recurrence when postsurgical inflammation and inflammatory disease are present (i.e., abscesses, colitis, rectal fistula). The physiological [18F]FDG uptake in the GI and genitourinary tracts due to the excretion of the tracer itself can mimic but also hide pathological sites. The risk of false-negative findings is high in the presence of miliary liver metastatic spread, due to the physiological uptake of [18F]FDG in the liver parenchyma and to a low lesion-to-background ratio or low [18F]FDG uptake in diffuse peritoneal effusion. Besides anatomical sites, lesion size is another important factor affecting PET accuracy and may be responsible for false-negative results. This is true especially in lymph node or hepatic lesions <1 cm in diameter, near the technique’s lower limit of effective spatial resolution. Finally, high patient blood glucose levels (>150 mg/dL) can deteriorate the [18F]FDG-PET image quality, and some metastatic lesions, especially those in the liver, can be missed . This is why blood glucose levels should be accurately kept under control with at least 6 h fasting before scanning. A meta-analysis by Huebner et al. evaluated the influence of false-positive and false-negative results on [18F]FDG-PET sensitivity and specificity in patients with recurrent disease . The final data showed that false positives had a greater impact than false negatives. In fact, the sensitivity of whole-body [18F]FDG-PET resulted high (97%), with similar rates for the detection of liver (91–96%) and pelvic (94%) involvement. Specificity values in the evaluation of recurrence differed for total body (76%) and liver and pelvis (97–99%) due to the greater likelihood of false-positive results in extrahepatic and extrapelvic regions than in isolated organs. Furthermore, a study by Akhurst et al.  on a group of patients who underwent [18F]FDG-PET for presurgical staging demonstrated that sensitivity was lower in those who received neoadjuvant chemotherapy due to the risk of the stunning phenomenon that leads to false-negative results when [18F]FDG-PET is performed too early after the end of treatment.
Treatment Response Evaluation
The identification of responders to chemotherapy is of interest for selecting patients who may be expected to benefit from continued treatment and for selecting those who could be treated with other drugs. Evaluation of response to treatment is ordinarily based on morphological assessment of target lesions and of changes in lesion diameter over time. Currently, the Response Evaluation Criteria in Solid Tumors (RECIST) is the most widely used set of rules to define disease response to treatment: complete response is defined as disappearance of target lesions at morphological imaging; partial response, a minimum reduction of 30% in lesion diameter; disease progression, a minimum increase of 20% in lesion diameter or appearance of new lesions; and stable disease, neither partial response nor disease progression . With [18F]FDG-PET came the need to have similar criteria for metabolic response, but consensus is still lacking. A significant decrease or increase in [18F]FDG uptake in target lesions during treatment has always been considered as a sign of treatment response or disease progression, respectively; nevertheless, lacking standardized limits and standardized timing of response assessment, each study uses its own criteria. One limitation to [18F]FDG-PET is its limited ability to detect minimal residual disease below the range of system spatial resolution. [18F]FDG uptake is detectable in lesions measuring 5–10 mm in diameter, which correspond to about 108–109 tumor cells. But even with this limitation, a negative PET scan during or at the end of treatment is predictive of good prognosis since it indicates disease response. Furthermore, the interval required for a positive [18F]FDG-PET/CT scan to become negative during treatment is a prognostic factor and a predictive element for final tumor response. If after 2 cycles of chemotherapy a PET scan is negative, as demonstrated in lymphomatous disease, the chances of obtaining remission at the end of the treatment are high, whereas the chances of remission with a few more chemotherapy cycles are lower if PET scans taken early at the beginning of treatment remain persistently positive [78, 79, 80]. Treatment response evaluated by [18F]FDG-PET is clearly related to a better overall survival and disease-free survival in most types of tumors. Metabolic response to treatment is normally evaluated quantitatively by measuring variation in SUVmax (standardized uptake value), which is a more practical and reproducible way than with qualitative visual methods, even if many studies have employed the latter, with good stratification of subsequent prognosis [81, 82, 83, 84].
PET combined with magnetic resonance imaging (PET/MRI ) seems to be a promising modality in different fields of tumor imaging. With the high soft tissue contrast of MRI and the superior ability of [18F]FDG-PET to detect vital tumor tissue prior to morphological changes, the advent of combined PET/MRI will open new perspectives in noninvasive imaging. The combination of PET with MRI also opens up options to acquire multimodal molecular imaging parameters simultaneously. This may contribute to a more detailed characterization of molecular processes in vivo [120, 121, 122]. Some studies also report results for colorectal cancer. Paspulati et al. reported their initial experience showing a high diagnostic accuracy of PET/MRI in T staging of rectal cancer compared with PET/CT. In addition, PET/MRI shows at least comparable accuracy in N and M staging as well as restaging to PET/CT. However, the small sample size limits the possibility to assume these results as definitive. It is expected that PET/MRI would yield higher diagnostic accuracy than PET/CT considering the high soft tissue contrast provided by MRI compared with CT, but larger studies are necessary to fully assess the benefit of PET/MRI in colorectal cancer .
Radiotherapy Volume Planning
[18F]FDG-PET is often used in clinical practice to identify target volume in radiotherapy treatment, especially in lung cancer [124, 125, 126, 127]. Some studies also report results for colorectal cancer. Promising preliminary results in esophageal, pancreatic, and anorectal cancers and colorectal liver metastasis suggest that [18F]FDG-PET might provide additional information useful in target volume delineation. Poor image resolution and a low sensitivity for lymph node detection currently limit its widespread implementation . Ciernik et al. demonstrated that PET/CT-derived planning target volume (PTV) is as accurate as CT-derived PTV . In the future, perhaps PET/CT alone will be sufficient for planning radiotherapy target volume.
Therapy with Transarterial 90Y-Microspheres
In unresectable liver metastases and advanced liver metastases, radioembolization treatment with microspheres containing the beta emitter yttrium-90 is becoming a valid alternative to other treatments such as chemoembolization and radiofrequency. Microspheres are injected into an artery and, because of their diameter (20 to 60 μm), become entrapped by embolization in the microvascular tissues. The half-life of yttrium-90 is 64.1 h, and the administered dose is closely correlated with body surface area and tumor burden. Although few studies have evaluated its efficacy and feasibility to date, the results are promising in terms of tumor response and overall survival. A study by Whitney et al. evaluating application of this technique for liver metastases from different cancers, including colorectal cancer, demonstrated that it reduces tumor burden and can be followed by surgical resection of metastases . In the bulk of studies, tumor response is based on CT according to RECIST, but there is also mounting evidence that [18F]FDG-PET could be a useful tool and a more accurate technique even in this field to better characterize tumor response according to metabolic criteria. Necrosis, inflammatory, or fibrotic processes can lead to an increase in lesion size after treatment, which can be interpreted as disease progression at anatomic imaging [131, 132, 133, 134]. Wong et al. showed that [18F]FDG-PET detected more partial responses than CT, as clinically confirmed by the decrease in serum CEA levels . In phase I–II studies, therapy with yttrium-90 microspheres can be combined with adjuvant chemotherapy to increase tumor radiosensitivity with good patient tolerability [136, 137, 138, 139]. The most common side effects of this treatment are abdominal pain, transient hepatotoxicity with elevated transaminase, hyperbilirubinemia, and hypersplenism; occasional cases of important neutropenia possibly induced by bone marrow irradiation when combined with adjuvant chemotherapy have been reported . Further studies on large-scale patient populations are needed to confirm these preliminary results.
Endocrine tumors can be found in the GI tract and in the rectal tract in particular. Their management, treatment, and prognosis differ substantially from adenocarcinomas. Oftentimes, they are discovered after the onset of local symptoms such as rectorrhagy. Prognosis is closely correlated with tumor size and local extension. Frequently, a simple endoscopic resection is sufficient for obtaining complete remission; more complex surgery is chosen as first intention treatment for more advanced local tumors. Distant metastases are infrequent. Tumor extension is local in almost 70% of cases. Nuclear medicine offers an array of imaging techniques to study endocrine tumors, all of which are based on the affinity these tumors have for somatostatin receptors [141, 142]. Historically, 111In-DTPA-octreotide scintigraphy is the most widely used technique to characterize the primary tumor and perform disease staging and follow-up of endocrine tumors. The sensitivity of this technique in endocrine tumor staging is between 60% and 100%, and it depends on tumor differentiation grade, somatostatin receptor density, origin, site, and size [143, 144]. Other approaches for evaluating intestinal endocrine tumor are now available: 18F-DOPA-PET (18F-6-fluoroDOPA), [11C]HTP-PET ([11C]-5-hydroxytryptophane), 68Ga-DOTA-TOC, and 68Ga-DOTA-NOC, all tracers with an affinity for somatostatin receptors or that are involved in endogenous amine metabolism. Although several studies on small groups of patients have shown the superiority of these techniques over traditional somatostatin analog scintigraphy [145, 146, 147], further studies are needed to confirm their accuracy and to identify standard recommendations for their use [148, 149, 150, 151, 152, 153, 154, 155].
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