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Abstract: A 61-year-old man underwent splenopancreasectomy for a 3-cm neuroendocrine tumor of the body of the pancreas (G2, pT1 pN0, Ki67 3%). Five months after surgery 68 Ga-DOTATOC PET/CT showed increased radiotracer uptake in a solid tissue of the splenic fossa, possibly referring to a splenosis nodule. After 19 months, a further 68 Ga-DOTATOC PET/CT showed a significant functional and dimensional increase of the previously detected tissue and the appearance of a new finding in the left lateral abdominal wall. In the suspicion of neuroendocrine tumor relapse, the patient underwent surgical excision of the documented lesions. Histology showed splenosis in both nodules., Competing Interests: Conflicts of interest and sources of funding: G.R. received speaker and consultant honoraria from AAA and Bracco Imaging, respectively. The other authors have no relevant financial or nonfinancial interests to disclose. The authors declare that no funds, grants, or other supports were received during the preparation of this manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET., Methods: After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus., Results: A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (from 6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive., Conclusion: Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and 18 F-FDG-PET/CT parameters (when available) were also correlated., Methods: Among 551 patients who underwent SSTR-PET/CT with 68 Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, 18 F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman's rank correlation test., Results: Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUV max values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUV max values corresponding to negative IHC and higher SUV max values to positive IHC (p = 0.002)., Conclusion: This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUV max values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available., (© 2022. The Author(s).)

Purpose: Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine neoplastic syndrome associated with a greater risk of endocrine tumor development like pancreatic neuroendocrine tumors (p-NET), with different clinical characteristics from sporadic ones. This paper aims to compare clinical, hystological and morphological aspects of p-NET in patients affected from MEN1 (MEN1+) and not-affected ones (MEN1-)., Methods: We performed a retrospective observational study. Data was collected between December 2010 and December 2015, including patients with a histological diagnosis of p-NET and radiological imaging. We compared clinical, histological, radiological, and prognostic aspects of MEN+ p-NET with MEN-1 p-NET., Results: Of the 45 patients enrolled, 13 MEN1+ and 21 MEN1- cases were analyzed. Frequency of not secreting p-NETs and insulin secreting p-NETs, histopathological grades and Ki67 expression were superimposable between MEN1+ and MEN1- patients. MEN1+ pNETs are more often multicentric compared to MEN1- pNETs. Frequency of liver and nodes metastatic spread was higher in MEN1- p-NET compared to MEN1+ p-NET. Analyzing p-NET according to the disease outcome, we found that recovered and stable p-NETs in MEN1+ patients, compared to MEN1- cases, are diagnosed at lower age (p = 0.04/p = 0.002) and that are more frequently multifocal lesions (p = 0.009/p = 0.002)., Conclusions: In our study pNETs in MEN1+ and pNETs in MEN1- don't significantly differ for prognosis but only for clinical features. p-NET stage disease and prognosis can be positively influenced by early diagnosis and screening in index patients' first-degree relatives.

Objective: The aim of the study was to assess the value and potential pitfalls of Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) in patients with suspected pancreatic neuroendocrine neoplasms (pNEN)., Methods: Consecutive patients referred for Ga-DOTANOC PET/CT for suspected pNEN between May 1, 2011, and October 31, 2014, were retrospectively assessed. Scan data were compared with cytological/histological final diagnosis. Pancreatic neuroendocrine neoplasm detection rate was determined on per-patient and per-lesion basis. Maximum standardized uptake values of lesions were determined., Results: Fifty-eight patients with 65 lesions were enrolled. Twelve patients had nonconfirmed diagnosis; of these, 7 were positive and 5 negative at PET/CT. Of 46 patients with confirmed diagnosis, 36 had pNEN; of these, 33 were positive, 1 negative, and 2 nonevaluable at PET/CT. Ten patients had non-NE lesions, of which 8 were positive, 1 negative, and 1 nonevaluable at PET/CT. Of 48 patients with positive PET/CT, 8 proved to have non-NE lesions, of which 6 were intrapancreatic accessory spleen. No significant maximum standardized uptake values difference was found between pNEN and non-NE lesions., Conclusions: Intrapancreatic accessory spleen is an important pitfall in Ga-DOTANOC PET/CT for suspected pNEN. Cytological/histological confirmation is mandatory before any surgical procedure is undertaken.

Objectives: The aims of this study were to investigate the added value of diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET) evaluation and to compare magnetic resonance imaging (MRI) to Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) results., Methods: Morphological MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per-patient and per-lesion detection rates (pDR and lDR, respectively) were calculated. Apparent diffusion coefficient values were compared among pNET and surrounding and normal pancreas (control group, 18 patients). Apparent diffusion coefficient and standardized uptake value (SUV) values were compared among different grading and staging groups., Results: No statistically significant differences in PET/CT and MRI session detection rates were found (morphological MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; Ga-DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI + PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value was significantly lower compared with surrounding and normal parenchyma (P < 0.01). The apparent diffusion coefficient and SUV values of pNETs among different grading and staging groups were not statistically different., Conclusions: Conventional MRI, DW-MRI + T2-w sequences, and Ga-DOTANOC PET/CT can be alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in patients with clinical suspicion but negative conventional imaging findings. However, the consensus reading of the 3 techniques seems the best approach.

A 77-year-old man was referred to our center for a suspected neuroendocrine neoplasm in the pancreatic tail, incidentally detected at CT. Ga DOTANOC PET/CT showed intense tracer uptake in the pancreatic lesion. At MRI, the lesion was similar to the spleen on all sequences, suggesting the presence of intrapancreatic accessory spleen. A Tc-colloid SPECT/CT scan performed to differentiate spleen tissue from neuroendocrine tumor revealed a focal uptake in the pancreatic lesion, thus confirming the presence of ectopic spleen and avoiding unnecessary surgery.

We report a rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome caused by a metastatic neuroendocrine tumor (NET) of the pancreas detected by PET/CT using different tracers. A 43-year-old female patient with Cushing syndrome (CS) by suspected ectopic ACTH secretion underwent a 68Ga-DOTANOC and a 18F-FDG PET/CT. Both these functional imaging techniques revealed increased tracer uptake in a pancreatic mass and multiple liver metastases. Histology showed the presence of a mildly differentiated pancreatic NET. 68Ga-DOTANOC PET/CT may be a useful functional imaging method, complementary to 18F-FDG PET/CT, in detecting ACTH-secreting pancreatic NETs.

We report the case of a pulmonary neuroendocrine tumor (NET) incidentally detected by F-CH PET/CT performed during restaging in a 68-year-old patient affected by prostate cancer. To clarify the nature of the pulmonary lesion, the patient underwent a CT-guided biopsy which revealed the presence of a pulmonary NET. A subsequent Ga-DOTANOC PET/CT demonstrated the somatostatin receptor expression in the pulmonary lesion. The patient underwent a right lung lobectomy; at pathology, a well-differentiated NET was confirmed. Our case highlights that pulmonary NETs should be considered in the differential diagnosis of pulmonary lesions showing uptake of radiolabeled choline.

Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns ((18)F-DOPA and (11)C-5-HTP) or specific receptor expression ((68)Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of (18)F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, (11)C-5-HTP performs better than (18)F-DOPA even though its use is hampered by its complex production and limited availability and experience; (68)Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, (68)Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy.

Unlabelled: Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs., Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91-95%) and 91% (95% CI: 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.

Purpose: Somatostatin receptor scintigraphy with [(111)In]-diethylene triamine pentaacetate acid (DTPA)-octreotide is an accurate method for detecting neuroendocrine tumours (NETs) but often does not provide clear anatomical localisation of lesions. The aim of this study was to assess the clinical usefulness of anatomical-functional image fusion., Materials and Methods: Fifty-four patients with known or suspected NET were included in the study. Planar and single-photon-emission computed tomography (SPECT) imaging was performed using a dual-head gamma camera equipped with an integrated X-ray transmission system, and the images were first interpreted alone by two nuclear medicine physicians and then compared with SPECT/CT fusion images together with a radiologist. The improvement provided by SPECT/CT in the interpretation of SPECT data alone and any modification in patient management were recorded., Results: Fusion images improved SPECT interpretation in 23 cases, providing precise anatomical localisation of increased tracer uptake in 20 cases and disease exclusion in sites of physiological uptake in 5. In 10 patients, SPECT/CT allowed definition of the functional significance of lesions detected by diagnostic CT. SPECT/CT data modified clinical management in 14 cases by changing the diagnostic approach in 8 and the therapeutic modality in 6., Conclusions: Our study demonstrates that image fusion is clearly superior to SPECT alone, allowing precise localisation of lesions and reducing false-positive results.

Neuroendocrine tumors (NETs) are rare neoplasms, which are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. Radiolabeled metaiodobenzylguanidine (MIBG) was the first radiopharmaceutical used to specifically depict and localize catecholamine-secreting tumors (pheochromocytomas, paragangliomas, and neuroblastomas) and is still regarded as a first-choice imaging technique for diagnosis and follow-up; in patients with malignant disease, MIBG scintigraphy is an essential step to select patients for (131)I-MIBG therapy. Scintigraphy with (111)In- or (99m)Tc-labeled somatostatin analogs has become the main imaging technique for NETs, particularly those expressing a high density of somatostatin receptors, such as gastroenteropancreatic tumors; this procedure is used routinely for localizing the primary tumor, evaluating disease extension, monitoring the effect of treatment and for selecting patients for radioreceptor therapy. Since the recent development of hybrid machines, it has been possible to obtain images that simultaneously hold both anatomic (computed tomography [CT]) and functional (single-photon emission computed tomography [SPECT] or positron emission tomography [PET]) information, with great impact on diagnostic accuracy. Significant improvements have been made during the past few years with the development of highly specific radiopharmaceuticals for PET studies that reflect the different metabolic pathways of NETs, such as glucose metabolism ((18)F-fluorodeoxyglucose), the uptake of hormone precursors ((11)C-5-hydroxytryptophan, (11)C- or (18)F-dihydroxyphenylalanine, (18)F-fluorodopamine), the expression of receptors ((68)Ga-labeled somatostatin analogs), as well as the synthesis, storage, and release of hormones ((11)C-hydroxyephedrine and others). Among these radiopharmaceuticals, (68)Ga-labeled somatostatin analogs are increasingly used in specialized centers in Europe for PET and PET/CT imaging and show very promising results with high diagnostic sensitivity. New somatostatin analogs with different receptor affinity as well as other peptides are currently under investigation and will further improve our diagnostic and therapeutic capabilities in the future.

Introduction: Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) is a valuable diagnostic tool for patients with neuroendocrine tumors (NET). To date, a meta-analysis about the diagnostic accuracy of this functional imaging method is lacking. Aim(s): To meta-analyze published data about the diagnostic performance of SMSR PET or PET/CT in patients with NET. Materials and methods: A comprehensive literature search of studies published in PubMed, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NET was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or gastroenteropancreatic (GEP) NET were selected (medullary thyroid tumors and paragangliomas were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR-PET or PET/CT in NET. Results: Seventeen studies comprising 587 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NET were 93% (95% CI, 91-95%) and 91% (95% CI, 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. Conclusion: In patients with suspicious thoracic and/or GEPNET, SMSR PET or PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious NET. [ABSTRACT FROM AUTHOR]