A 75-year-old man with a previous history of left nephrectomy for clear cell renal cell carcinoma in remission was underwent 68 Ga-DOTATATE PET/CT imaging for evaluation of pancreatic body lesion. It showed a mass with intense 68 Ga-DOTATATE uptake in the pancreatic corpus. During the follow-up of the patient who did not want to undergo surgery, 18 F-FDG PET/CT scan was performed due to the increase in the size of the mass, and mild FDG uptake was detected in the pancreatic corpus lesion, and histopathological examination was confirmed as renal cell carcinoma metastasis.

Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009-2022) were retrospectively examined. First-line lanreotide vs. octreotide cohorts were matched 1:1 by propensity scores for demographics, tumour characteristics, and diagnosis year. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier analysis and the Cox proportional hazards model. Results: Among 441 patients, 310 were matched (155 in both the octreotide and lanreotide groups). First-line SSA was monotherapy (63.5%) or combination with other medications (36.5%). A total of 77% of second-line patients (188/244) maintained their initial SSA medication in combination with other therapies. Radioligand therapy with lanreotide (N = 72; 29.5%) or octreotide (N = 70; 28.7%) was the most common second-line treatment. First-line lanreotide and octreotide cohorts had similar median PFS (15.5; 95% CI: 13.6-19.1 vs. 14.0; 95% CI: 12.0-15.8 months), despite octreotide having a 36% higher likelihood of moving to the second line than lanreotide (95% CI: 1.05-1.76, p = 0.018). Multiple metastases (HR = 1.45; p = 0.004, 95% CI: 1.13-1.87) and Ki-67 > 20% (HR = 2.34; p < 0.001, 95% CI: 1.43-3.83) were significantly associated with the worst PFS. First-line lanreotide patients had a median OS of 10.4 years (95% CI: 7.5-NA) and octreotide 9.2 years (95% CI: 7.3-NA) (p = 0.537). Bone metastases increased death risk by 91% (p = 0.014; 95% CI: 1.14-3.20). Conclusions: SSA monotherapy is the main first-line treatment and most subsequent treatments include SSA with additional medications. Cohorts had similar PFS/OS, but octreotide demonstrated a 36% significantly higher likelihood of moving to the second-line treatment.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and biologically diverse group of tumors that are challenging to image. 68Ga-DOTATATE PET/CT is the most sensitive imaging tool for these tumors, and while its use has increased over time, its clinical impact remains unclear, particularly for clinical scenarios involving surveillance after treatment. We sought to reassess its clinical utility across all stages.

Retrospective study of pathologically confirmed GEP-NET patients between 1/1/2020 and 9/1/2022 at a tertiary care center. Demographic, clinical, and radiographic data were analyzed. The primary objective was to determine if PET/CT use was associated with a change in clinical management. The secondary objective was to determine if PET/CT was superior in identifying primary or metastatic lesions compared to traditional imaging.

One hundred twenty-four patients with GEP-NETs underwent 207 PET/CT scans. The majority of scans were obtained for disease surveillance (70.2%) or staging (37.9%), and the remaining (3.2%) were used to aid in diagnosis or before PRRT initiation (3.2%). Following PET/CT scan, 51 patients (41.1%) had a change in clinical management, with change being higher among those with metastatic disease (44.9% vs. 14.5%). Of the 124, 72 patients had traditional imaging available for comparison. In this subgroup, 34 patients (47.2%) had new lesions identified on PET/CT that were not identified using traditional imaging resulting in a change in management in 79.4% favoring patients with M1 versus M0 disease (26.9% M0 vs. 58.7% M1, p = 0.010).

68Ga-DOTATATE PET/CT imaging is clinically most useful for initial staging and in surveillance and monitoring response to therapy in the metastatic setting. It is least useful for surveillance in the early-stage setting and does not support its use following curative intent surgery. It remains superior to unlabeled imaging in sensitivity and the additional disease burden detected is highly likely to change management.

Somatostatin is a peptide that plays a variety of roles such as neurotransmitter and endocrine regulator; its actions as a cell regulator in various tissues of the human body are represented mainly by inhibitory effects, and it shows potent activity despite its physiological low concentrations. Somatostatin binds to specific receptors, called somatostatin receptors (SSTRs), which have different tissue distributions and associated signaling pathways. The expression of SSTRs can be altered in various conditions, including tumors; therefore, they can be used as biomarkers for cancer cell susceptibility to certain pharmacological agents and can provide prognostic information regarding disease evolution. Moreover, based on the affinity of somatostatin analogs for the different types of SSTRs, the therapeutic range includes conditions such as tumors, acromegaly, post-prandial hypotension, hyperinsulinism, and many more. On the other hand, a number of somatostatin antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs. The aim of this review is to present in detail the principal characteristics of all five SSTRs and to provide an overview of the associated therapeutic potential in neoplasias.

Pancreatic neuroendocrine tumors (PNETs) arise from neuroendocrine cells and are a rare class of heterogenous tumors with increasing incidence. The diagnosis, staging, treatment, and prognosis of PNETs depend heavily on identifying the histologic features and biological mechanisms. Here, the authors provide an overview of the diagnostic workup (biomarkers and imaging), grade, and staging of PNETs. The authors also explore associated genetic mutations and molecular pathways and describe updated guidelines on surgical and systemic treatment modalities.

Neuroendocrine tumors (NETs) are relatively uncommon heterogeneous neoplasms arising from endocrine and neuronal origin cells showing highly variable clinical behavior. By the time these tumors are discovered, up to 14% of patients with histologically proven NETs have metastasis, with the liver as the most frequently affected organ. Sometimes, no known primary site can be identified via routine imaging. Neuroendocrine tumors of unknown origin carry a poorer prognosis (compared with metastatic NETs with a known primary site) because of a lack of tailored surgical intervention and appropriate medical therapy (eg, chemotherapy or targeted therapy). A multimethod approach is frequently used in the trial to accurately determine the primary site for NETs of unknown primary sites and may include clinical, laboratory, radiological, histopathological, and surgical data. New molecular techniques using the genomic approach to identify the molecular signature have shown promising results. Various imaging modalities include ultrasound, computed tomography (CT), dual-energy CT, magnetic resonance imaging, and functional and hybrid imaging (positron emission tomography/CT, positron emission tomography/magnetic resonance imaging); somatostatin receptor imaging with new tracers is frequently used in an attempt for localization of the primary site.

Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention.

Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models' bACC, SN, SP, PPV and NPV were collected and compared (Kruskal-Wallis, Mann-Whitney).

LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*).

In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.

Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells. NEN are ideally suited for a theragnostic approach due to their specific expression of somatostatin receptors (SSTR). SSTR imaging of NEN dates back to the 1980s, but has evolved recently due to the introduction of more sensitive SSTR PET radiotracers. SSTR PET is a primary imaging modality for identifying NEN and characterizing SSTR expression. SSTR PET is complementary to anatomic imaging for assessing tumor response to treatment. SSTR PET is mandated to determine eligibility for peptide receptor radionuclide therapy. Here, the role of imaging to aid management of NEN is reviewed.

Molecular imaging with antibodies radiolabeled with positron-emitting radionuclides combines the affinity and selectivity of antibodies with the sensitivity of Positron Emission Tomography (PET). PET imaging allows the visualization and quantification of the biodistribution of the injected radiolabeled antibody, which can be used to characterize specific biological interactions in individual patients. This characterization can provide information about the engagement of the antibody with a molecular target such as receptors present in elevated levels in tumors as well as providing insight into the distribution and clearance of the antibody. Potential applications of clinical PET with radiolabeled antibodies include identifying patients for targeted therapies, characterization of heterogeneous disease, and monitoring treatment response.Antibodies often take several days to clear from the blood pool and localize in tumors, so PET imaging with radiolabeled antibodies requires the use of a radionuclide with a similar radioactive half-life. Zirconium-89 is a positron-emitting radionuclide that has a radioactive half-life of 78 h and relatively low positron emission energy that is well suited to radiolabeling antibodies. It is essential that the zirconium-89 radionuclide be attached to the antibody through chemistry that provides an agent that is stable in vivo with respect to the dissociation of the radionuclide without compromising the biological activity of the antibody.This Account focuses on our research using a simple derivative of the bacterial siderophore desferrioxamine (DFO) with a squaramide ester functional group, DFO-squaramide (DFOSq), to link the chelator to antibodies. In our work, we produce conjugates with an average ∼4 chelators per antibody, and this does not compromise the binding of the antibody to the target. The resulting antibody conjugates of DFOSq are stable and can be easily radiolabeled with zirconium-89 in high radiochemical yields and purity. Automated methods for the radiolabeling of DFOSq-antibody conjugates have been developed to support multicenter clinical trials. Evaluation of several DFOSq conjugates with antibodies and low molecular weight targeting agents in tumor mouse models gave PET images with high tumor uptake and low background. The promising preclinical results supported the translation of this chemistry to human clinical trials using two different radiolabeled antibodies. The potential clinical impact of these ongoing clinical trials is discussed.The use of DFOSq to radiolabel relatively low molecular weight targeting molecules, peptides, and peptide mimetics is also presented. Low molecular weight molecules typically clear the blood pool and accumulate in target tissue more rapidly than antibodies, so they are usually radiolabeled with positron-emitting radionuclides with shorter radioactive half-lives such as fluorine-18 (t1/2 ∼ 110 min) or gallium-68 (t1/2 ∼ 68 min). Radiolabeling peptides and peptide mimetics with zirconium-89, with its longer radioactive half-life (t1/2 = 78 h), could facilitate the centralized manufacture and distribution of radiolabeled tracers. In addition, the ability to image patients at later time points with zirconium-89 based agents (e.g. 4-24 h after injection) may also allow the delineation of small or low-uptake disease sites as the delayed imaging results in increased clearance of the tracer from nontarget tissue and lower background signal.

Liver transplantation (LT) for neuroendocrine liver metastases (NELM) is still in debate. Studies comparing LT with liver resection (LR) for NELM are scarce, as patient selection is heterogeneous and experience is limited. The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.

A scoping literature search on LT and LR for NELM was performed with PubMed, including English articles up to March 2023.

International guidelines recommend LR for NELM in resectable, well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies. Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival. In highly selected patients (based on the Milan criteria) with unresectable NELM, oncologic results of LT are promising. Prognostic factors include tumor biology (G1/G2) and burden, waiting time for LT, patient age and extrahepatic spread. Based on low-level evidence, LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR. The benefits of LT were lost in patients beyond the Milan NELM-criteria.

With adherence to strict selection criteria especially tumor biology, LT for NELM is becoming a valuable option providing oncologic benefits compared to LR. Recent evidence suggests even stricter selection criteria with regard to tumor biology.

New digital detectors and block-sequential regularized expectation maximization (BSREM) reconstruction algorithm improve positron emission tomography (PET)/magnetic resonance (MR) image quality. The impact on image quality may differ from analogue PET/computed tomography (CT) protocol. The aim of this study is to determine the potential reduction of injected [68Ga]Ga-DOTA-TATE activity for digital PET/MR with BSREM reconstruction while maintaining at least equal image quality compared to the current analogue PET/CT protocol.

NEMA IQ phantom data and 25 patients scheduled for a diagnostic PET/MR were included. According to our current protocol, 1.5 MBq [68Ga]Ga-DOTA-TATE per kilogram (kg) was injected. After 60 min, scans were acquired with 3 (≤ 70 kg) or 4 (> 70 kg) minutes per bedposition. PET/MR scans were reconstructed using BSREM and factors β 150, 300, 450 and 600. List mode data with reduced counts were reconstructed to simulate scans with 17%, 33%, 50% and 67% activity reduction. Image quality was measured quantitatively for PET/CT and PET/MR phantom and patient data. Experienced nuclear medicine physicians performed visual image quality scoring and lesion counting in the PET/MR patient data.

Phantom analysis resulted in a possible injected activity reduction of 50% with factor β = 600. Quantitative analysis of patient images revealed a possible injected activity reduction of 67% with factor β = 600. Both with equal or improved image quality as compared to PET/CT. However, based on visual scoring a maximum activity reduction of 33% with factor β = 450 was acceptable, which was further limited by lesion detectability analysis to an injected activity reduction of 17% with factor β = 450.

A digital [68Ga]Ga-DOTA-TATE PET/MR together with BSREM using factor β = 450 result in 17% injected activity reduction with quantitative values at least similar to analogue PET/CT, without compromising on PET/MR visual image quality and lesion detectability.

There is a boom in imaging biomarker-driven companion and complementary diagnostics (CDx) for cancer, which brings opportunity for personalized medicine. Whether adoption of these technologies is likely to be cost-effective is a relevant question, and studies on this topic are emerging. Despite the growing number of economic evaluations, no review of the methods used, quality of reporting, and potential risk of bias has been done. We report a systematic review to identify, summarize, and critique the cost-effectiveness evidence for the use of biomarker-driven and imaging-based CDx to inform cancer treatments.

The Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Systematic literature searches until 30 December 2022 were performed in PubMed, Web of Science, Medline, Embase, and Scopus for economic evaluations of imaging biomarker-based CDx for cancer. The inclusion and exclusion of studies were determined by pre-specified eligibility criteria informed by the 'Patient, Intervention, Comparison, Outcome' (PICO) framework. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) was used to assess the quality of reporting, and the Bias in Economic Evaluation (ECOBIAS) was used to examine the potential risk of bias of included studies.

A total of 12 papers were included, with eight model-based and four trial-based studies. Implementing biomarker-driven, imaging-based CDx was reported to be cost-effective, cost saving, or dominant (cost saving and more effective) in ten papers. Inconsistent methods were found in the studies, and the quality of reporting was lacking against the CHEERS reporting guideline. Several potential sources of 'risk of bias' were identified. These should be acknowledged and carefully considered by researchers planning future health economic evaluations.

Despite favorable results towards the implementation of imaging biomarker-based CDx for cancer, there is room for improvement regarding the quantity and quality of economic evaluations, and that is expected as the awareness of current study limitations increases and more clinical data become available in the future.

Molecular changes in malignant tissue can lead to an increase in the expression levels of various proteins or receptors that can be used to target the disease. In oncology, diagnostic imaging and radiotherapy of tumors is possible by attaching an appropriate radionuclide to molecules that selectively bind to these target proteins. The term "theranostics" describes the use of a diagnostic tool to predict the efficacy of a therapeutic option. Molecules radiolabeled with γ-emitting or β+-emitting radionuclides can be used for diagnostic imaging using single photon emission computed tomography or positron emission tomography. Radionuclide therapy of disease sites is possible with either α-, β-, or Auger-emitting radionuclides that induce irreversible damage to DNA. This Focus Review centers on the chemistry of theranostic approaches using metal radionuclides for imaging and therapy. The use of tracers that contain β+-emitting gallium-68 and β-emitting lutetium-177 will be discussed in the context of agents in clinical use for the diagnostic imaging and therapy of neuroendocrine tumors and prostate cancer. A particular emphasis is then placed on the chemistry involved in the development of theranostic approaches that use copper-64 for imaging and copper-67 for therapy with functionalized sarcophagine cage amine ligands. Targeted therapy with radionuclides that emit α particles has potential to be of particular use in late-stage disease where there are limited options, and the role of actinium-225 and lead-212 in this area is also discussed. Finally, we highlight the challenges that impede further adoption of radiotheranostic concepts while highlighting exciting opportunities and prospects.

Merkel cell carcinoma (MCC) but metastases to the pancreas are very rare. There are only a few cases of isolated metastases of MCC to the pancreas. Because of this rarity, it can be wrongly diagnosed as a neuroendocrine tumor of the pancreas(pNET), especially the poorly differentiated neuroendocrine carcinoma (PNEC) subtype, in which the treatment is vastly different than that of MCC with isolated metastases of the pancreas.

An electronic search of the PubMed and google scholar databases was performed to obtain the literature on MCC with pancreatic metastases, using the following search terms: Merkel cell carcinoma, pancreas, and metastases. Results are limited to the following available article types: case reports and case series. We identified 45 cases of MCC with pancreatic metastases from the PubMed and Google Scholar database search and examined their potential relevance. Only 22 cases with isolated pancreatic metastases were taken for review including one case that we encountered.

The results from our review of cases of isolated pancreatic metastases of MCC were compared to the characteristics of the poorly differentiated pancreatic neuroendocrine tumor (PNEC). We found the following: (a) MCC with isolated pancreatic metastases occurred at an older age than PNEC and with male gender predominance (b) Most of the metastases occurred within 2 years of initial diagnosis of MCC (c) Resection of pancreatic mass was the first line treatment in case of resectable PNECs whereas resection of metastases was infrequently performed in MCC with pancreatic metastases.

Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions.

Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68 Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion.

Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions.

Our results show that 68 Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost.

PRRT can be an option for all-grade GEP-NETs, but selecting patients is challenging. In this scenario, clinical-pathological and radiological characteristics, such as pre-treatment Ga-68 DOTA PET/CT, might have the potential to help.

A retrospective chart review was conducted on advanced GEP-NETs treated with at least one PRRT dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Krenning Score (KS), and the maximum standardized uptake value (SUVmax) were derived from the pre-treatment scans. A maximally selected rank statistics test was used for SUVmax simple cut point estimate.

Among 36 patients, 19 had primary pancreatic tumors. The numbers of G1, G2, and G3 tumors were 10, 18, and 7, respectively. During a median follow-up of 90.5 months, 4 patients died. Median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 (p = 0.001). Median PFS was 23 months, with G3 showing lower PFS compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2-31.0; p = 0.001)].

PRRT provides long-term PFS in patients with G1/G2 GEP-NETs independent of clinical characteristics and primary site. G3 has worse survival, but selected patients may experience long OS after PRRT treatment.

Neuroendocrine tumors (NET) may affect the heart by cardiac metastasis or carcinoid heart disease. NET metastasis to the heart is rare, with limited data characterizing it. We sought to evaluate 68Ga-DOTATATE PET scan imaging features and associated cardiac imaging characteristics where available in those with NET cardiac metastases. 68Ga-DOTATATE positron emission tomography (PET)/CT scans performed on patients with gastroenteropancreatic (GEP) NET at our institution were reviewed for cardiac involvement. Those identified with cardiac metastases had their electronic medical record, transthoracic echocardiogram (TTE) and cardiac magnetic resonance imaging (MRI) reviewed for characterization. From a total of 1426 68Ga-DOTATATE PET/CT scans performed on patients with GEP-NET, 25 (1.75%) had cardiac uptake consistent with metastasis. Of these, 22 had myocardial metastases (29 distinct myocardial lesions: left ventricle - 16, right ventricle - 6, and ventricular septum -7) and 3 had periradial lymph node involvement only. NET patients with cardiac metastases as identified by DOTATATE scan did not appear to have any hemodynamically significant TTE features, aside from those (2/25) who had concomitant carcinoid heart disease. Of the 14 patients who had available TTE for review, only one with high metastatic cardiac tumor burden had detectable cardiac mass. Of the 6 cases who had available MRI, all had metastatic cardiac lesions seen with excellent correlation with tumor localization on 68Ga-DOTATATE PET scan. 68Ga-DOTATATE PET has excellent capability for the diagnosis of cardiac NET metastasis. Cardiac MRI may provide further anatomic and tissue characterization evaluation. Those with myocardial NET metastases without carcinoid heart disease did not have significant hemodynamic effect based on echocardiographic criteria.

Sinonasal cancers are uncommon malignancies with a generally unfavorable prognosis, often presenting at an advanced stage. Their high rate of recurrence supports close imaging surveillance and the utilization of functional imaging techniques. Whole-body 18F-FDG PET/CT has very high sensitivity for the diagnosis of sinonasal malignancies and can also be used as a "metabolic biopsy" in the characterization of some of the more common subgroups of these tumors, though due to overlap in uptake, histological confirmation is still needed. For certain tumor types, radiotracers, such as 11C-choline, and radiolabeled somatostatin analogs, including 68Ga-DOTATATE/DOTATOC, have proven useful in treatment planning and surveillance. Although serial scans for posttreatment surveillance allow the detection of subclinical lesions, the optimal schedule and efficacy in terms of survival are yet to be determined. Pitfalls of 18F-FDG, such as post-surgical and post-radiotherapy crusting and inflammation, may cause false-positive hypermetabolism in the absence of relapse.

Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.

To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery.

This retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE.

Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040).

SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.

The aim of this retrospective study was to compare the diagnostic accuracy of somatostatin receptor (SSR)-PET/CT to liver MRI as reference standard in the evaluation of hepatic involvement in neuroendocrine tumors (NET).

An institutional database was screened for "SSR" imaging studies between 2006 and 2021. 1000 NET Patients (grade 1/2) with 2383 SSR-PET/CT studies and matching liver MRI in an interval of +3 months were identified. Medical reports of SSR-PET/CT and MRI were retrospectively evaluated regarding hepatic involvement and either confirmed by both or observed in MRI but not in SSR-PET/CT (false-negative) or in SSR-PET but not in MRI (false-positive).

Metastatic hepatic involvement was reported in 1650 (69.2%) of the total 2383 SSR-PET/CT imaging studies, whereas MRI detected hepatic involvement in 1685 (70.7%) cases. There were 51 (2.1%) false-negative and 16 (0.7%) false-positive cases. In case of discrepant reports, MRI and PET/CT were reviewed side by side for consensus reading. SSR-PET/CT demonstrated a sensitivity of 97.0% (95%CI: 96.0%, 97.7%), a specificity of 97.7% (95%CI: 96.3%, 98.7%), a PPV of 99.0% (95%CI: 98.4%, 99.4%) and NPV of 93.0% (95%CI: 91.0, 94.8%) in identifying hepatic involvement. The most frequent reason for false-negative results was the small size of lesions with the majority < 0.6 cm.

This study confirms the high diagnostic accuracy of SSR-PET/CT in the detection of hepatic involvement in NET patients based on a patient-based analysis of metastatic hepatic involvement with a high sensitivity and specificity using liver MRI imaging as reference standard. However, one should be aware of possible pitfalls when a single imaging method is used in evaluating neuroendocrine liver metastases in patients.

Radiolabeled somatostatin analogs are increasingly used in the diagnosis and treatment of neuroendocrine tumors. Diagnostic imaging with 68Ga-DOTATATE PET/CT has demonstrated the improved sensitivity in detecting primary and metastatic neuroendocrine lesions compared with conventional imaging and prior generation somatostatin receptor imaging. Peptide receptor radionuclide therapy with 177Lu-DOTATATE is now frequently included in the management of neuroendocrine neoplasms, with prospective randomized control studies demonstrating its beneficial impact on survival and quality of life. Nonetheless, peptide rector radionuclide therapy is still considered palliative rather than curative and may be accompanied by adverse effects.

Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.

The imaging report is essential for the communication between physicians in patient care. The information it contains must be clear, concise with evidence-based conclusions and sufficient to support clinical decision-making. In recent years, several classification schemes and/or reporting guidelines for PET have been introduced. In this manuscript, we will review the classifications most frequently used in oncology for interpreting and reporting 18F-FDG PET imaging in lymphoma, multiple myeloma, melanoma and head and neck cancers, PSMA-ligand PET imaging for prostate cancer, and 68Ga-DOTA-peptide PET in neuroendocrine tumors (NET).

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.

Radiopharmaceutical analysis is limited by conventional methods. Radio-HPLC may be inaccurate for some compounds (e.g., 18F-radiopharmaceuticals) due to radionuclide sequester. Radio-TLC is simpler, faster, and detects all species but has limited resolution. Imaging-based readout of TLC plates (e.g., using Cerenkov luminescence imaging) can improve readout resolution, but the underlying chromatographic separation efficiency may be insufficient to resolve chemically similar species such as product and precursor-derived impurities. This study applies a systematic mobile phase optimization method, PRISMA, to improve radio-TLC resolution. The PRISMA method optimizes the mobile phase by selecting the correct solvent, optimizing solvent polarity, and optimizing composition. Without prior knowledge of impurities and by simply observing the separation resolution between a radiopharmaceutical and its nearest radioactive or non-radioactive impurities (observed via UV imaging) for different mobile phases, the PRISMA method enabled the development of high-resolution separation conditions for a wide range of 18F-radiopharmaceuticals ( [18F]PBR-06, [18F]FEPPA, [18F]Fallypride, [18F]FPEB, and [18F]FDOPA). Each optimization required a single batch of crude radiopharmaceutical and a few hours. Interestingly, the optimized TLC method provided greater accuracy (compared to other published TLC methods) in determining the product abundance of one radiopharmaceutical studied in more depth ( [18F]Fallypride) and was capable of resolving a comparable number of species as isocratic radio-HPLC. We used the PRISMA-optimized mobile phase for [18F]FPEB in combination with multi-lane radio-TLC techniques to evaluate reaction performance during high-throughput synthesis optimization of [18F]FPEB. The PRISMA methodology, in combination with high-resolution radio-TLC readout, enables a rapid and systematic approach to achieving high-resolution and accurate analysis of radiopharmaceuticals without the need for radio-HPLC.

We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68Ga-DOTATOC; 68Ga-DOTATATE; 68Ga-DOTANOC; 99mTc-EDDA/HYNIC-TOC; 64Cu-DOTATATE; and 111In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111In-DTPA-Octreotide and 68Ga-DOTATOC/TATE. Few papers compared 64Cu-DOTATATE and 68Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111In-DTPA-Octreotide, 99mTc-EDDA/HYNIC-TOC, 68Ga-DOTATATE/TOC and 64Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.

The aim of this study was to assess the utility of serum chromogranin A (CgA) along the clinical pathway of patients with neuroendocrine tumors (NETs).

A retrospective review of medical records was conducted of patients with NET who had at least 1 measurement of CgA between January 2015 and April 2021 at a large metropolitan Australian hospital. Chromogranin A was classified as increased or decreased if there was at least a 25% change in sequential levels and was compared with disease response by anatomical or functional imaging if within 6 weeks (considered concurrent).

Of 102 patients with NETs, 67 had at least 1 serum CgA level: 50 had been ordered during diagnostic workup, of which 33 were elevated (sensitivity: 66%; 95% confidence interval, 51%-79%). Of 129 CgA results concurrent with imaging, the sensitivity for detecting progressive disease was 28% (95% confidence interval, 15%-44%).

Our findings support previous concerns that CgA adds little value in clinical decision-making.

The aim of this study was to identify and evaluate the role of 68 Ga-DOTA-somatostatin analog (SSA) PET/CT in guiding treatment for patients with neuroendocrine tumors (NETs) based on published literature, with specific focus on the ability of PET/CT to impact clinical management and predict peptide receptor radionuclide therapy (PRRT) response.

A systematic literature search of articles up to December 2021 was performed using PubMed and Scopus. Eligible studies included ≥10 patients with confirmed or suspected NETs who had undergone pretreatment staging 68 Ga-DOTA-SSA PET/CT. A meta-analysis using the random-effects model was conducted to determine the overall change in management after PET/CT, whereas PET/CT-derived parameters that correlated with PRRT outcome were summarized from studies that assessed its predictive capabilities.

A total of 39 studies were included in this systemic review, of which 2266 patients from 24 studies were included for meta-analysis. We showed that PET/CT resulted in a change in clinical management in 36% (95% confidence interval, 31%-41%; range, 3%-66%) of patients. Fifteen studies consisting of 618 patients examined the prognostic ability of 68 Ga-DOTA-SSA PET/CT for PRRT. Of those, 8 studies identified a higher pretreatment SUV to favor PRRT, and 4 identified PET-based radiomic features for somatostatin receptor heterogeneity to be predictive of PRRT response.

Along with its diagnostic abilities, 68 Ga-DOTA-SSA PET/CT can impact treatment decision-making and may predict PRRT response in patients with NETs. More robust studies should be conducted to better elucidate the prognostic role of somatostatin receptor PET/CT in optimizing treatment for clinical outcome.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors in childhood. Up to 40% of PPGL are currently thought to be associated with a hereditary predisposition. Nuclear medicine imaging modalities such as fluorodeoxyglucose positron emission tomography (¹⁸ F-FDG PET), ⁶⁸ Ga-DOTATATE PET, and ¹²³ I-metaiodobenzylguanidine (¹²³ I-MIBG) scintigraphy play an essential role in the staging, response assessment, and determination of suitability for targeted radiotherapy in patients with PPGL. Each of these functional imaging modalities targets a different cellular characteristic and as such can be complementary to anatomic imaging and to each other. With the recent US Food and Drug Administration approval and increasing use of ⁶⁸ Ga-DOTATATE for imaging in children, the purpose of this article is to use a case-based approach to highlight both the advantages and limitations of DOTATATE imaging as it is compared to current radiologic imaging techniques in the staging and response assessment of pediatric PPGL, as well as other neuroendocrine malignancies.

⁶⁸Ga-labeled somatostatin analog (SSA) PET/CT is now a standard-of-care component in the management of neuroendocrine tumors (NETs). However, treatment response for NETs is still assessed with morphologic size measurements from other modalities, which can result in inaccuracy about the disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared with morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. Methods: The clinical and imaging data of 327 NET patients were collected at Memorial Sloan Kettering Cancer Center between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 wk and were excluded if they had any intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated SSA. Lesions were excluded if they contained necrotic components or were lobulated. This exclusion resulted in 94 lesions in 20 patients. The FTV for each lesion was evaluated with a hand-drawn assessment and 3 automated techniques: 50% threshold from SUV_max, 42% threshold from SUV_max, and background-subtracted lesion activity. These measurements were compared with volume calculated from morphologic volume measurements. Results: The FTV calculation methods showed varying correlations with morphologic volume measurements. FTV using a 42% threshold had a 0.706 correlation, hand-drawn volume from PET imaging had a 0.657 correlation, FTV using a 50% threshold had a 0.645 correlation, and background-subtracted lesion activity had a 0.596 correlation. The Bland-Altman plots indicated that all FTV methods had a positive mean difference from morphologic volume, with a 50% threshold showing the smallest mean difference. Conclusion: FTV determined with thresholding of SUV_max demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method was more accurate than FTV calculated from hand-drawn volume assessments. Threshold-based automated FTV assessment promises to better determine disease extent and prognosis in patients with NETs.

68Ga-DOTATATE PET/CT is an imaging technique used in the diagnosis of neuroendocrine tumors. Since renal cell carcinoma (RCC) expresses the somatostatin receptors, 68Ga-DOTATATE PET/CT could be used in the surveillance of RCC. However, limited cases showing 68Ga-DOTATATE uptake in the metastases of RCC have been reported before. Herein, we report a case of a 55-year-old woman with a history of left nephrectomy for clear cell renal cell carcinoma 2 years before, and referred to 68Ga-DOTATATE PET/CT for the evaluation of adrenal mass. 68Ga-DOTATATE PET/CT showed intense 68Ga-DOTATATE uptake on the adrenal mass. Histopathology of the adrenal mass confirmed the diagnosis of clear cell renal cell carcinoma metastasis.

Neuroendocrine tumors are a heterogeneous group of neoplasms that arise from the peptide-producing cells of the neuroendocrine system. Different functional imaging methods have been suggested to diagnose NETs. There is still not enough evidence to recommend 68Ga-DOTATATE as a standard diagnostic tool in NETs. Therefore, the aim of this study was to assess the value of 68Ga-DOTATATE scan in detecting NETs.

This was a cross-sectional study. All patients with a pathologically confirmed NET tumor referred to Masih Daneshvari Hospital affiliated to Shahid Beheshti University of Medical Sciences entered the study. Patients underwent a 68Ga-DOTATATE PET/CT. All statistical analysis were performed by SPSS software version 18.

Forty patients with a mean age of 48.1±15.80 years entered the study. Twenty-one (52.5%) were male and 19 (47.5%) female. In the studied patients, neuroendocrine tumor was present in 19 cases (47.5%) in pancreas and gastrointestinal tract, 9 (22.5%) in lung, 3 (7.5%) in mediastinum and adrenal gland, 6 cases (5%) in liver and 3 other sites. There was no significant association between mean age and gender with primary location of the tumor. The mean SUVmax was 11.62±20.02 and the the mean tumor size was 38.25±31.35 mm. The mean size of the metastasis was 40.55±24.53 mm. The mean percentage of ki-67 was 12.54±18.40. There was no significant correlation between SUVmax of the lesion and age (r=0.063, P=0.701), tumor size (r=-0.63, P=0.067) or Ki-67 (r=0.011, P=0.960). In 20 cases, metastases were reported, of which 14 were (70%) in the liver, 3 in the lungs (15%), 2 in the gastrointestinal and cervical lymph nodes, and 1 in the bones and pancreas(%5).

68Ga-DOTA-peptide PET/CT could find the primary or metastasis sites of NETs with good quality images. In general, this modality can enhance the management in patients with NETs.

^123/131I-MIBG scintigraphy has shown a high specificity for imaging pheochromocytoma and paraganglioma however with low sensitivity due to low spatial resolution. ¹²⁴I-MIBG PET may overcome this limitation to improve the staging of patients with (suspected) pheochromocytoma. Methods: We analyzed the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of ¹²⁴I-MIBG PET in 43 consecutive patients with suspected (recurrence of) pheochromocytoma using histopathological (n = 25) and clinical validation (n = 18) as standard of truth. Furthermore, we compared ¹²⁴I-MIBG PET versus contrast enhanced CT (CE-CT) per-patient and per-lesion detection rate of ¹²⁴I-MIBG PET in 13 additional patients with known metastatic malignant pheochromocytoma (MMP). Results: ¹²⁴I-MIBG PET/CT was positive in 19/43 (44%) patients with suspected pheochromocytoma. Presence of pheochromocytoma was confirmed in 22/43 (51%). ¹²⁴I-MIBG PET/CT sensitivity, specificity, PPV, NPV were 86%, 100%, 100%, 88%, respectively. ¹²⁴I-MIBG PET was positive in 11/13 (85%) MMP patients. Combined ¹²⁴I-MIBG PET and CE-CT detected 173 lesions, of which 166 (96%) and 118 (68%) were visible on ¹²⁴I-MIBG PET and CE-CT, respectively. Discussion: ¹²⁴I-MIBG PET detects pheochromocytoma with high accuracy at initial staging and high detection rate at re-staging. Superior diagnostic performance aids guidance of surgical and medical management including personalized ¹³¹I-MIBG therapy.

68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation.

This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVmax of the most intense lesion and the most intense organ-matched lesion were determined. Demographics and pathology results for Ki-67 and MI were collected from the electronic medical record. Correlations and trends for correlations of SUVmax to Ki-67 and MI were performed using Kruskal-Wallis and Cuzick trend tests.

A trend for an association between SUVmax and Ki-67 grade was found; median SUVmax of Ki-67 < 3%, 3-20%, and > 20% was 35.2, 31.8, and 12.8 (p = 0.077), respectively. There was also a trend between SUVmax and Ki-67 categories in organ-matched lesions (p = 0.08). The median organ-matched SUVmax of MI < 2, 2-20, and > 20 lesions was 34.2, 18, and 21.7, respectively, (Cuzick trend test p = 0.066). The median SUVmax for small bowel, pancreatic, and other primary locations was 27.6, 46.9, and 9.3 (p < 0.01), respectively.

The association between 68Ga-DOTATATE SUVmax, histologic grade, and primary site of NEN demonstrates its potential use for prognostication, or potentially as a surrogate for histologic grading when biopsy is not possible.

Neuroendocrine tumors (NETs) are a relatively rare entity; however, the incidence and prevalence of these tumors are increasing, likely attributed to improved diagnostic accuracy. The diagnosis of suspected NETs is facilitated by clinical symptoms, laboratory test abnormalities such as elevated chromogranin-A, and other diagnostic modalities such as the use of computed tomography scans, magnetic resonance imaging scans, positron emission tomography (PET) scans, and biopsy. The expression of high levels of somatostatin receptors in NETs enables the use of a specialized PET scan using the radiolabeled somatostatin analogues 68Ga-DOTATATE. The sensitivity and specificity of 68Ga-DOTATATE PET is very high for the diagnosis of NETs, but the specificity decreases especially with no clear symptoms and with only borderline elevated tumor markers. We present a case of a suspected NET, which was initially diagnosed as a metastatic NET by virtue of a positive 68Ga-DOTATATE PET scan; however, on biopsy it was revealed to be a squamous cell carcinoma originating from the head and neck.

Sinonasal tumors are relatively rare and radiographically challenging to evaluate due to their wide variety of pathologies and imaging features. However, sinonasal tumors possessing somatostatin receptor overexpression have the benefit of utilizing a multimodality anatomic and functional imaging for a more comprehensive evaluation. This is particularly evident with esthesioneuroblastoma, with computed tomography and magnetic resonance imaging defining the anatomic extent of the tumor, whereas somatostatin receptor imaging, particularly with gallium-68 DOTATATE positron emission tomography/computed tomography, is used to assess the presence of metastatic disease for staging purposes as well as in the surveillance for tumor recurrence. In addition, areas which accumulate gallium-68 DOTATATE are potentially amenable to treatment with peptide receptor radionuclide therapy. In this manner, a combined approach of anatomic and functional imaging is critical for optimal imaging evaluation and treatment strategy of patients with sinonasal tumors.

In addition to gastroenteropancreatic neuroendocrine neoplasms, a wide variety of tumors express somatostatin receptors. Somatostatin receptor imaging, heavily utilized in neuroendocrine oncology, may also have utility in the diagnosis of other neoplasms and raises the possibility of potential therapeutic options. We describe the case of a 60-year-old man who underwent 68Ga-DOTATATE PET/CT, demonstrating an avid invasive pituitary macroadenoma. This mass was persistent and refractory despite traditional treatment options. Because of the avidity, 177Lu-DOTATATE therapy was offered, although not ultimately performed, demonstrating a potential treatment for challenging cases utilizing the principles of theranostics.

Several studies have demonstrated the effectiveness of somatostatin receptor (SSTR)-targeted imaging for diagnosis, staging, evaluating the possibility of treatment with cold somatostatin analogs, as well peptide receptor radionuclide therapy (PRRT), and evaluation of treatment response. PET with ⁶⁸Ga-labeled somatostatin analogs provides excellent sensitivity and specificity for diagnosing and staging neuroendocrine tumors (NETs). Metabolic imaging with PET with fludeoxyglucose ¹⁸F/computed tomography (CT) complements the molecular imaging with ⁶⁸Ga-SSTR PET/CT toward a personalized therapy in NET patients. The documented response rate of PRRT in NET summing up complete response, partial response, minor response, and stable disease is 70% to 80%.

OBJECTIVE. The purpose of this article is to review the clinical manifestations, endocrine tumors types, and multimodality diagnostic tools available to physicians involved in the management of patients with multiple endocrine neoplasia (MEN) syndrome, in addition to discussing relevant imaging findings and appropriate imaging follow-up. CONCLUSION. Thorough knowledge of the spectrum of tumors associated with MEN gene mutations aids in the screening, diagnostic workup, and posttreatment monitoring of patients with MEN-related gene mutations.

A 37-year-old active duty male Air Force instructor pilot, with no prior medical history, was found unresponsive at his home after awakening with symptoms of altered mental status when the Emergency Medical Service (EMS) was called. The patient was found to be hypoglycemic with a glucose of 37 mg/dL. The patient recovered after administration of a dextrose bolus. Further investigation revealed that over the last several years, the patient exhibited symptoms of lightheadedness and tremors if fasted greater than 3 hours. Further clinical workup strongly suggested the presence of a neuroendocrine tumor. Initial imaging studies to include a multiphasic dedicated pancreatic computed tomography (CT) scan did not demonstrate a pancreatic lesion. However, the utilization of an innovative new nuclear medicine imaging modality, a 68Ga-Dotatate PET/CT, clearly demonstrated a 19 × 16 mm lesion of the distal pancreatic tail, which guided surgical resection. He underwent a robotic-assisted laparoscopic distal pancreatectomy, pathologically characterized as an insulinoma. The patient's symptoms immediately resolved with no recurrence over the next 6 months. The pilot was granted a waiver, returning him to his flying duties. The 68Ga-Dotatate PET/CT enabled the identification of an otherwise occult pancreatic neuroendocrine tumor ultimately leading to this patient's definitive cure and the salvage of this military asset's aviation career.