Diagnostic imaging of typical lung carcinoids: relationship between MDCT, 111In-Octreoscan and 18F-FDG-PET imaging features with Ki-67 index.

AIMS: This study analyses the capability of contrast-enhanced multi-detector computed tomography (MDCT) and spectrum of molecular imaging to characterize typical carcinoids (TCs) of lung and their relationship with Ki-67 index. MATERIALS AND METHODS: We analysed 68 patients with histological diagnosis of pulmonary TC, which underwent both MDCT and nuclear molecular imaging (somatostatin receptor scintigraphy/SPECT with 111In-pentetreotide and 18F-FDG-PET/CT) at staging evaluation before surgery. The MDCT scan was reviewed for the following features: size, margins, contrast enhancement, presence of calcifications, bronchial obstruction, lymph nodes and metastases. In 111In-pentetreotide SPECT, tumour/non-tumour ratio was measured at 4- and 24-h post-injection and the per cent difference was calculated (T/NT%). FDG uptake was measured as the ratio between lesion SUVmax and liver SUVmean (SUV ratio). All imaging features were correlated between them and with Ki-67 index. RESULTS: Forty-four of the 68 lesions (65%) were in the right lung. In MDCT, scan lesions appeared as a well-defined nodule in 44 patients (65%) and irregular mass in 24 patients (35%). Contrast intense enhancement was present in 53 patients (78%), calcifications in 20 patients (29%) and bronchial obstruction in 24 patients (35%). Lymph nodes and metastasis were present in 13 (19%) and 15 (22%) patients. Ki-67 index was negatively correlated with T/NT% and positively with SUV ratio; T/NT% and SUV ratio were inversely correlated. The presence of irregular margins and metastases was negatively related to T/NT%. The presence of a mass, irregular margins, bronchial obstruction, lymph nodes and metastasis was positively related to higher SUV ratio. The presence of irregular margins, bronchial obstruction, lymph nodes and metastases was significantly correlated with a higher grade of Ki-67 index. CONCLUSIONS: MDCT and nuclear molecular imaging are important to characterize lung TCs. The majority of TCs appear as a well-defined nodule generally not associated with extra-thorax signs. We found a significant correlation between some MDCT aspects, nuclear medicine features and Ki-67 index. The association of MDCT and nuclear medicine imaging may be useful in predicting proliferative activity and prognosis of lung TCs.

Somatostatin receptor expression in non-classical locations - clinical relevance?

In-111 pentetreotide (Octreoscan) is a radiolabeled somatostatin analog with high binding affinity to somatostatin receptors (SSTR) used in somatostatin receptor scintigraphy (SRS). Pentetreotide labelled with In-111 is widely used due to its high affinity to SSTR 2 and 5. SSTR are expressed on neuroendocrine cells as well as several non-neural and non-endocrine cells with varying levels of density. We retrospectively reviewed articles and publications related to octreoscan accumulation in sites that classically do not have high concentrations of SSTR as well as in organs and tissues from diseases which are not usually diagnosed by octreoscan. The significance of a positive uptake as assessed by octreoscan in non-somatostatin receptor related diseases is not fully understood yet. Localization of octreotide in non-oncological disease states such as inflammation is due to presence of SSTR in activated immunological cells, over-expression by activated cells in the respective tissue and SSTR expression by blood vessels. In granulomatous diseases, over-expression of SSTR2 preferential binding sites were detected in epitheloid and giant cells. The purpose of the current study is to identify octreoscan localization in non-somatostatin receptor related disease sites to better understand the mechanism of this nonspecific accumulation which may help expand the clinical utilization of functional imaging utilizing somatostatin receptor scintigraphy in diagnosis and perhaps therapy.

Clinical Usefulness of Somatostatin Receptor Scintigraphy in Japanese Patients with Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND/AIMS: Somatostatin receptor (SSTR) scintigraphy (SRS) is the standard imaging modality for evaluation of gastroenteropancreatic neuroendocrine tumor (GEP-NET) in Western countries. However, this modality was not approved in Japan until recently. The purpose of this study was to evaluate the clinical efficacy of SRS for detecting GEP-NET in Japanese patients. METHODS: Japanese patients with advanced GEP-NET were enrolled and evaluated by the SRS and CT. We also compared SRS and immunohistochemical expression of SSTR type 2a (SSTR2a). RESULTS: We enrolled 16 patients and the primary sites were the pancreas in 9, the stomach in 1, the small intestine in 2, the colon in 3, and unknown in 1. SRS showed positive findings in 3 (100%) of grade 1 (G1) and in 12 (92.3%) of grade 2 (G2) lesions. In the liver, SRS and CT detected lesions in 13 and 14 cases, respectively. The concordance rate of SSTR2a expression with SRS findings was 93.8% in the whole body and 92.9% in the liver. CONCLUSIONS: SRS could detect almost all of G1 and G2. SRS could be useful to detect lesions, with a high concordance rate with CT and pathological findings. We confirmed that SRS is a useful and reliable modality for Japanese patients.

Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1.

CONTEXT: Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. PURPOSE: To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. DESIGN AND SETTING: Single-institution prospective comparative study PATIENTS AND METHODS: Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. RESULTS: The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on (68)Ga-DOTA-TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of (68)Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and (18)F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with (68)Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. CONCLUSIONS: Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In-pentetreotide in the investigation of MEN1 patients.

Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours.

OBJECTIVES: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality. METHODS: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities. RESULTS: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton. CONCLUSION: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT. KEY POINTS: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT.

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

PURPOSE: Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). MATERIALS AND METHODS: This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. RESULTS: Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4 h, 2.6 ± 1.0; 24 h, 2.2 ± 1.0; kidney: 4 h, 8.9 ± 1.8; 24 h, 7.0 ± 2.0; and spleen; 4 h, 11.3 ± 4.5; 24 h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4 h, p < 0.001; 24 h, p < 0.001) (4 h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24 h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). CONCLUSION: We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms.

OBJECTIVES: We investigated the detectability of somatostatin receptor scintigraphy (SRS) for neuroendocrine neoplasms (NEN). METHODS: From January 2016 to October 2020, 125 SRS examinations using indium-111 pentetreotide performed for patients with NEN lesions were retrospectively evaluated. The detection rate of NEN lesions was determined according to histopathological classification by primary site and by organ. RESULTS: At least one NEN lesion was detected in 73% (91/125) with a positive Krenning score of ≥2 in SRS. The detection of abdominal NENs (gastrointestinal tract, 38; pancreas, 62; and others, 14) was 89% (49/55) for neuroendocrine tumor (NET)-grade (G) 1, 78% (32/41) for NET-G2, 66% (2/3) for NET-G3, 31% (4/13) for neuroendocrine carcinoma (NEC), 100% (1/1) for mixed neuroendocrine-non-neuroendocrine neoplasm, and 0% (0/1) for non-classified NEN. That of thoracic NENs was 33% (2/6) for typical carcinoid tumor and 40% (2/5) for atypical carcinoid tumor. For a total of 226 organ lesions, hepatic lesions were 76% (58/76); pancreatic lesions, 61% (31/51); lymph node lesions, 77% (27/35); bone lesions, 83% (20/24); duodenal lesions, 82% (9/11); and other lesions, 41% (11/27). CONCLUSION: The detectability of SRS for NEN in Japan was verified at a center, and its usefulness was confirmed.

Utility of Multimodality Approach Including Systemic FGF23 Venous Sampling in Localizing Phosphaturic Mesenchymal Tumors.

Context: Tumor-induced osteomalacia (TIO) is one of the most common forms of acquired fibroblast growth factor 23 (FGF23)-related hypophosphatemia and is usually caused by phosphaturic mesenchymal tumors (PMTs). Although the complete resection of PMTs can cure TIO, preoperative localization of tumors by standard imaging modalities is often challenging. In addition to 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET) and 111In-pentetreotide scintigraphy (SRS), systemic FGF23 venous sampling (FGF23VS) has been used to help localize PMTs in specialized institutions. Objective: This study aimed to evaluate the diagnostic performance of each imaging test and their combinations in localizing PMTs. Methods: In an observational retrospective study of patients with adult-onset FGF23-related osteomalacia who underwent all 3 imaging studies (FDG-PET, SRS, and FGF23VS), the rate of successful preoperative localization of the tumors was evaluated only in the patients with pathological diagnoses of PMTs, considering the possibility that pathogenesis of patients without identified tumors might be due to other causes such as late-onset hereditary FGF23-related hypophosphatemia. Results: A total of 30 Japanese patients with TIO (median age, 60 years [range, 28-87 years]; 10 women [33.3%]) were included in the study. The success rate of preoperative localization for each test and combinations of 2 or 3 tests among 18 patients with PMTs was as follows: 72% (FDG-PET), 72% (SRS), 94% (FGF23VS), 89% (FDG-PET, SRS), 100% (FDG-PET, FGF23VS), 94% (SRS, FGF23VS), and 100% (FDG-PET, SRS, and FGF23VS). Conclusion: We observed the highest localization rate of PMTs in patients with identified PMTs with the combination of FDG-PET and FGF23VS.

Development of a new quantification method using partial volume effect correction for individual energy peaks in 111In-pentetreotide SPECT/CT.

Objectives: Somatostatin receptor scintigraphy (SRS) using 111In-pentetreotide has no established quantification method. The purpose of this study was to develop a new quantitative method to correct the partial volume effect (PVE) for individual energy peaks in 111In-pentetreotide single-photon emission computed tomography (SPECT). Methods: Phantom experiments were performed to construct a new quantitative method. In the phantom experiments, a NEMA IEC body phantom was used. Acquisition was performed using two energy peaks (171 keV and 245 keV) on the SPECT/CT system. The volume of interest was set at each hot sphere and lung insert in the SPECT images of each energy peak, and the recovery coefficient (RC) was calculated to understand the PVE. A new quantitative index, the indium uptake index (IUI), was calculated using the RC to correct the PVE. The quantitative accuracy of the IUI in the hot sphere was confirmed. Case studies were performed to clarify the quantitative accuracy. In a case study, the relationship between the IUI and the Krenning score, which is used as a visual assessment, was evaluated for each lesion. Results: The obtained RCs showed that the energy peak at 171 keV was faster in recovering the effect of PVE than that at 245 keV. The IUI in the 17-mm-diameter hot sphere was overestimated by 4.8% and 8.3% at 171 keV and 245 keV, respectively, compared to the actual IUIs. The relationship between IUI and Krenning score was rs=0.773 (p<0.005) at sum, rs=0.739 (p<0.005) at 171 keV, and rs=0.773 (p<0.005) at 245 keV. Conclusion: We have developed a new quantification method for 111In-pentetreotide SPECT/CT using RC-based PVE correction for an individual energy peak of 171 keV. The quantitative accuracy of this method was high even for accumulations of less than 20 mm, and it showed a good relationship with the Krenning score; therefore, the clinical usefulness of IUI was demonstrated.

Mediastinal Cystic Parathyroid Adenoma Diagnosed by Somatostatin Receptor Scintigraphy.

A 71-year-old man complained of nausea and loss of appetite for eight months prior to admission. He was transported to a hospital with disorientation and diagnosed with primary hyperparathyroidism by laboratory examinations. However, ultrasonography, computed tomography, and technetium-99m labeled methoxyisobutyl isonitrile (99mTc-MIBI) with single-photon emission computed tomography did not yield definite results. In contrast, somatostatin receptor scintigraphy successfully identified the lesion responsible for the over-secretion of parathyroid hormone within the middle mediastinum. The tumor was successfully resected by surgery, and a histopathological analysis confirmed the parathyroid adenoma nature of the tumor.

Evaluation of a Correction Method for 111In-Pentetreotide SPECT Imaging of Gastroenteropancreatic Neuroendocrine Tumors.

The number of patients with the extremely rare disease gastroenteropancreatic (GEP) neuroendocrine tumor (NET) has increased rapidly in recent years. 111In-pentetreotide SPECT in somatostatin receptor scintigraphy has been used for the assessment of GEP NET patients. To diagnose GEP NET, appropriate selection of image correction parameters is critical. Correction methods may improve the 111In-pentetreotide SPECT image quality, but there is currently no standard technique. The purpose of this study was to determine the optimal correction parameter settings for 111In-pentetreotide SPECT. Methods: A phantom study produced images with a tumor-to-background ratio of as high as 16:1. A triple energy window was used for scatter correction (SC), and attenuation correction (AC) was CT-based. Correlation analysis was performed in 4 groups: no correction (NC), SC, AC, and combined SC with AC (CC). The 111In-pentetreotide SPECT results for 20 randomly selected patients (13 men and 7 women; age range, 37-81 y) with confirmed GEP NET were analyzed using data collected 4 h after injection of 111 MBq of 111In-pentetreotide. Emission data were reconstructed using ordered-subset expectation maximization (OSEM) with different settings. Different combinations of the correction parameters were used to analyze the contrast-to-noise ratios (CNRs) obtained with the phantom. In the clinical study, 20 GEP NET patients were used to evaluate the GEP NET lesion CNR by 4 different image correction methods obtained from 111In-pentetreotide SPECT images: NC, SC, AC, and CC. NC was used as a reference method. Results: The phantom study revealed that the optimal energy window in the photopeak for somatostatin receptor scintigraphy was 171 keV ± 10% and 245 keV ± 7.5%, and the optimal OSEM reconstruction conditions were 8 subsets and 6 iterations. Among the OSEM collection conditions, CC produced a significantly higher CNR than NC or SC (P < 0.05). In the clinical study, CC was found to increase the CNR (P < 0.05). Conclusion: CC improves the correction in 111In-pentetreotide SPECT studies, compared with NC, providing better contrast and sharper outlines of lesions and organs.

Lateral ectopic thyroid mimics carotid body tumor on Indium-111 pentetreotide scintigraphy.

A 34-year old woman with past history of anxiety, depression, and hypothyroidism resulting from prior total thyroidectomy for multinodular goiter presented with complaints of palpitations, sweating, and tachycardia. Clinical examination revealed a painless right lateral neck mass. USG/CT of the neck revealed the soft tissue mass located at the right carotid bifurcation. A subsequent Indium-111 pentetreotide somatostatin receptor scintigraphy (SRS) demonstrated tracer uptake in the mass. Hence, secretory carotid body tumor/paraganglioma was strongly suspected. However, post-surgical histopathological specimen revealed only benign thyroid follicles indicative of lateral ectopic thyroid with no evidence of neuroendocrine cells or malignancy. This case highlights the importance of considering lateral ectopic thyroid, a very rare entity, in the differential diagnosis for carotid bifurcation masses. Also highlighted is the false positivity from normal but ectopic thyroid tissue on Indium-111 pentetreotide SRS mimicking a paraganglioma.

111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden.

Eligibility for somatostatin receptor (SSTR) radionuclide therapy uses the qualitative Krenning score based on 111In-pentetreotide planar scintigraphy as was performed in the NETTER-1 trial. The purpose of this study was to determine the effect of using SSTR PET-based Krenning score in comparison to 111In-pentetreotide. Methods: This was a post hoc head-to-head comparison of 68Ga-DOTATATE-based and 111In-pentetreotide-based Krenning scores in 150 patients included in a prospective phase 2 study (NCT01967537). Patients were imaged using 68Ga-DOTATATE PET/CT, 111In-pentetreotide planar scintigraphy, and SPECT/CT within 1 wk. SSTR ligand uptake was graded using the Krenning score independently by 3 readers. Results: The detection rate of SSTR-expressing disease (Krenning scores 2-4) was 23%, 38%, and 72% with planar imaging, SPECT, and SSTR PET, respectively. The Krenning score was higher with SSTR PET (2.71 ± 1.74) than with planar imaging (0.75 ± 1.37; P < 0.001) or SPECT (1.23 ± 1.57; P < 0.001). In patients with a Krenning score of at least 3 on SSTR PET, the detection rate of planar imaging and SPECT was lower for lesions smaller than 2 cm than lesions 2 cm or larger: 15% and 24% versus 78% and 89%, respectively (P < 0.001). For lesions larger than 5 cm, Krenning scores between SSTR PET and 111In-pentetreotide were nearly equivalent. Lesion size did not have an impact on SSTR PET Krenning scores. Interreader agreement was higher for SSTR PET than for planar imaging or SPECT (0.79 vs. 0.67 and 0.50, respectively). Conclusion: SSTR PET results in higher Krenning scores than 111In-pentetreotide, particularly when lesions measured 2 cm or less. Small lesion size resulted in low Krenning scores using 111In-pentetreotide, but lesion size did not affect SSTR PET-based Krenning scores. The results of the NETTER-1 trial cannot be directly applied to patients with small lesions. Further study of peptide receptor radionuclide therapy in patients with small lesions negative on 111In-pentetreotide imaging and positive on SSTR PET is warranted.

Gamma Emitters in Pancreatic Endocrine Tumors Imaging in the PET Era: Is there a Clinical Space for 99mTc-peptides?

BACKGROUND: Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms, sporadic or familial, even being part of a syndrome. Their diagnosis is based on symptoms, hormonal disorders or may be fortuitous. The role of Nuclear Medicine is important, mainly because of the possibility of a theranostic strategy. This approach is allowed by the availability of biochemical agents, which may be labeled with radionuclides suitable for diagnostic or therapeutic purposes, showing almost identical pharmacokinetics. The major role for radiopharmaceuticals is connected with radiolabeled Somatostatin Analogues (SSA), since somatostatin receptors are highly expressed on some of the neoplastic cell types. DISCUSSION: Nowadays, in the category of radiolabeled SSA, although 111In-pentetreotide, firstly commercially proposed, is still used, the best choice for diagnosis is related to the so called DOTAPET radiotracers labeled with 68-Gallium (Ga), such as 68Ga-DOTATATE, 68Ga-DOTANOC, and 68Ga-DOTATOC. More recently, labeling with 64-Copper (Cu) (64Cu-DOTATATE) has also been proposed. In this review, we discuss the clinical interest of a SAA (Tektrotyd©) radiolabeled with 99mTc, a gamma emitter with better characteristics, with respect to 111Indium, radiolabeling Octreoscan ©. By comparing both pharmacokinetics and pharmacodynamics of Octreoscan©, Tektrotyd© and PET DOTA-peptides, on the basis of literature data and of our own experience, we tried to highlight these topics to stimulate further studies, individuating actual clinical indications for all of these radiotracers. CONCLUSION: In our opinion, Tektrotyd© could already find its applicative dimension in the daily practice of NETs, either pancreatic or not, at least in centers without a PET/CT or a 68Ga generator. Because of wider availability, a lower cost, and a longer decay, compared with respect to peptides labeled with 68Ga, it could be also proposed, in a theranostic context, for a dosimetry evaluation of patients undergoing Peptide Receptor Radionuclide Therapy (PRRT), and for non-oncologic indications of radiolabelled SSA. In this direction, and for a more rigorous cost/effective evaluation, more precisely individuating its clinical role, further studies are needed.

Rare Orbital Metastasis Originating From a Neuroendocrine Tumor.

BACKGROUND: This case study details a rare orbital metastasis originating from the gastrointestinal tract. A patient presented with proptosis of the right eye precipitated by a slow-growing orbital tumor. A biopsy confirmed a low-grade neuroendocrine tumor. Imaging studies were completed, with magnetic resonance (MR) imaging of the orbits providing the most detailed images of the mass. Fusion software images were created from the MR images and indium In 111 pentetreotide (octreoscan) studies, which confirmed the presence of the neuroendocrine carcinoid tumor. DISCUSSION: Orbital metastases are a rare condition associated with various symptoms, most commonly proptosis and diplopia. Imaging modalities, such as MR, computed tomography, and nuclear medicine technology, are instrumental in detecting and assessing these masses. Fusion imaging software can provide additional opportunities for facilities without hybrid scanners. The treatment of choice for orbital metastases is octreotide therapy; however, radiation therapy, partial or complete surgical removal of the tumor, and chemotherapy also are used. CONCLUSION: Traditional imaging techniques and fusion imaging techniques are essential for diagnosing and treating orbital metastases.

Diffuse Pancreatic Neuroendocrine Tumor: A Rare Presentation.

Diffuse involvement of the pancreas in neuroendocrine tumor is a rare presentation, and its appearance on In-111 pentetreotide scan has not been reported earlier in the literature. We present the whole body images from In-111 pentetreotide scan, contrast-enhanced computed tomography images, and histopathology correlation.

Imaging Somatostatin Receptor Activity in Neuroendocrine-differentiated Prostate Cancer.

Neuroendocrine-differentiated prostate cancer (NEPC) is a rare pathophysiology. We herein report a patient diagnosed with conventional prostate adenocarcinoma before hormone therapy, which was later diagnosed as NEPC. The nadir of prostate-specific antigen (PSA) was achieved once. However, adenocarcinoma changed to NEPC in recurrence, and the serum progastrin-releasing peptide (Pro-GRP) and neuron-specific enolase (NSE) values increased. A prostate needle biopsy revealed neuroendocrine differentiation. The chemotherapy regimen was changed, and somatostatin receptor scintigraphy (SRS) helped to determine the distribution and features of lesions as well as the effects of therapy. When prostate cancer worsens despite conventional therapy, NEPC should be considered.

68Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis.

68Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of 68Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. Methods: The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with 111In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. Results: The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with 111In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for 111In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Conclusion:68Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than 111In-octreotide. Although 68Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs.

Radioguided surgery (RGS) is a surgical technique that, using intra-operative probes, enables the surgeon to identify tissues preoperatively "marked" by a radiopharmaceutical. Somatostatin receptors (SSTRs) are present in the majority of neuroendocrine cells and may be over-expressed not only by tumor cells, but also by endothelial cells of peritumoral vessels, inflammatory cells and cells of the immune system, such as activated lymphocytes, monocytes and epithelioid cells. This extra neoplastic uptake is the rationale for the use of radiolabeled somatostatin analogs (SSAs) either in some tumors not expressing SSTRs or in various non-oncological diseases. The crucial point of RGS technique lays in the establishment of a favorable tumor-to-background ratio (TBR). A wide range of probe systems are available with different detectors and many radiopharmaceuticals have been experimented and utilized, mainly using g-detection probes; in order to widen RGS application field, newer approaches with b- or b+ emitting radioisotopes have also been proposed. Together with the consolidated clinical use, a promising and effective employment of RGS may be found in neuroendocrine tumors (NETs) using 111In-pentetreotide (OCT). RGS with OCT has been demonstrated useful in the management of patients with gastroenteropancreatic (GEP) tumors, lung, brain and breast cancer. Preoperative scintigraphy or PET with DOTA-peptides combined with RGS increases the rate of successful surgery. Preliminary studies with b- probes using 90Y-SSA suggest the possible interest of this approach in patients undergoing peptide receptor radiotherapy.

Non-functioning gastroenteropancreatic (GEP) tumors: a 111In-Pentetreotide SPECT/CT diagnostic study.

In a retrospective study performed in non-functioning GEP tumor patients we further investigated 111In-Pentetreotide SPECT/CT usefulness in diagnosis, staging and follow-up also evaluating whether the procedure may give more information than conventional imaging procedures (CIP), such as CT, MRI, US. We enrolled 104 consecutive patients with non-functioning GEP tumors, 30 in initial diagnosis and staging phases (IDS) and 74 in follow-up (FU). All patients underwent somatostatin receptor scintigraphy (SRS) whole body scan at 4, 24 and, if necessary, 48 hours followed by abdominal and chest SPECT/CT after 111In-Pentetreotide 148-222 MBq i.v. injection. The patients previously underwent 2 to 3 CIP. At both CIP and SPECT/CT, 34/104 patients were classified as no evidence of disease (NED); in 70/104 patients, neoplastic lesions were ascertained and 12 IDS and 17 FU were classified as not operable and treated with octeotride or chemotherapy. SPECT/CT and CIP were concordantly positive in 44 patients, while only CIP was positive in 6 cases and only SPECT/CT in 20. Both per-patient sensitivity and accuracy of SPECT/CT (91.4 and 94.2%, respectively) were higher than CIP (71.4 and 80.8%, respectively), but not significantly. Globally, 292 lesions were ascertained: 141 hepatic, 78 abdominal extra-hepatic and 73 extra-abdominal. CIP detected 191/292 (65.4%) lesions in 50 patients, while SPECT/CT 244/292 (83.6%) in 64, the difference being significant (p<0.0001). No false positive results were found at both SPECT/CT and CIP. Both SPECT/CT sensitivity and accuracy were higher than CIP in G1, G2, neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) patients, but significantly only for G1. Globally, SPECT/CT incremental value than CIP was 35.6%. SPECT/CT correctly modified CIP classification and patient management in 27.9% of cases, while it down-staged the disease than CIP in 9.6% of cases. However, the two procedures combined use could achieve the highest accuracy value. 111In-Pentetreotide SRS, acquired as SPECT/CT, showing high sensitivity and accuracy values, more elevated than CIP in the present study, can still have a wide employment in the routine diagnostic protocol of non-functioning GEP tumors with significant impact on patient management and therapy planning. The procedure is simple to perform, has limited cost and wide availability in all Nuclear Medicine Centers.