Search Results (44)

Background: [⁶⁸Ga]Ga-DOTATOC is widely used in PET imaging of neuroendocrine tumors (NETs) due to its high affinity for somatostatin receptors. Given the short physical half-life of gallium-68 (~68 min), rapid, reproducible, and GMP-compliant synthesis is essential for clinical application. Methods: An optimized cassette-based automated synthesis protocol was developed using a commercial cassette. Improvements included direct generator elution into the reactor without pre-purification, use of a SepPak^® C18 Plus Light cartridge for purification, replacement of HEPES with 0.3 M sodium acetate buffer (final pH ~3.8), and implementation of a non-vented sterile filter enabling automated pressure-hold integrity testing. Results: Across all batches, the synthesis yielded [⁶⁸Ga]Ga-DOTATOC with high radiochemical purity (> 97%) and reproducible decay-corrected radiochemical yields up to 88.3 ± 0.6%. Total synthesis time was approximately 13 min. The final product remained stable for at least 3 h post-synthesis. The use of acetate buffer eliminated the need for HEPES-specific testing, streamlining the workflow. Automated filter testing improved GMP-compliant documentation and reduced radiation exposure for personnel. Conclusions: This optimized, cassette-based synthesis protocol enables fast, high-yield, and GMP-compliant production of [⁶⁸Ga]Ga-DOTATOC. It supports clinical theranostic workflows by ensuring product quality, process standardization, and regulatory compliance. Full article

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from ⁶⁸Ge/⁶⁸Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications. Full article

Objective: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and the post-GKRS applications of PET for patient care. Methods: PubMed, Scopus, and ScienceDirect were searched in order to assemble relevant studies regarding the uses of PET in conjunction with GKRS for ICN treatment. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to identify relevant studies on the use of PET in conjunction with GKRS. Particular emphasis was placed on review articles and medical research investigating tumor delineation and post-operative care. Relevant studies were selected and assessed based on quality measures, including study design, sample size, and significance. Inclusion and exclusion criteria were used to examine the yield of the initial search (n = 105). After a secondary review, the included results were identified (n = 50). Results: This study revealed that PET imaging is highly accurate for the planning of GKRS. In fact, many cases indicate that it is more specific than traditional imaging modalities. PET is also capable of complementing traditional imaging techniques through combination imaging. This showed significant efficacy for the planning of GKRS for ICNs. Conclusions: While PET shows a multitude of applications for the treatment of ICNs with GKRS, further research is necessary to assemble a complete set of clinical guidelines for treatment specifications. Importantly, future studies need a greater standardization of methods and expanded trials with a multitude of radiotracers. Full article

Objectives: The aim of our study is to evaluate whether texture analysis of 68Ga-DOTATOC PET/CT images can predict clinical outcome in patients with neuroendocrine tumors (NET). Methods: Forty-seven NET patients who had undergone 68Ga-DOTATOC PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic (n = 35), bronchopulmonary (n = 8), and other (n = 4) districts. NET lesions were segmented using an automated contouring program and subjected to texture analysis, thus obtaining the conventional parameters SUVmax and SUVmean, volumetric parameters of the primary lesion, such as Receptor-Expressing Tumor Volume (RETV) and Total Lesion Receptor Expression (TLRE), volumetric parameters of the lesions in the whole-body, such as wbRETV and wbTLRE, and texture features such as Coefficient of Variation (CoV), HISTO Skewness, HISTO Kurtosis, HISTO Entropy-log₁₀, GLCM Entropy-log₁₀, GLCM Dissimilarity, and NGLDM Coarseness. Patients were subjected to a mean follow-up period of 17 months, and survival analysis was performed using the Kaplan–Meier method and log-rank tests. Results: Forty-seven primary lesions were analyzed. Survival analysis was performed, including clinical variables along with conventional, volumetric, and texture imaging features. At univariate analysis, overall survival (OS) was predicted by age (p = 0.0079), grading (p = 0.0130), SUVmax (p = 0.0017), SUVmean (p = 0.0011), CoV (p = 0.0037), HISTO Entropy-log₁₀ (p = 0.0039), GLCM Entropy-log₁₀ (p = 0.0044), and GLCM Dissimilarity (p = 0.0063). At multivariate analysis, only GLCM Entropy-log₁₀ was retained in the model (χ² = 7.7120, p = 0.0055). Kaplan–Meier curves showed that patients with GLCM Entropy-log₁₀ >1.28 had a significantly better OS than patients with GLCM Entropy-log₁₀ ≤1.28 (χ² = 10.6063, p = 0.0011). Conclusions: Texture analysis of 68Ga-DOTATOC PET/CT images, by revealing the heterogeneity of somatostatin receptor expression, can predict the clinical outcome of NET patients. Full article

Background: [⁶⁸Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [⁶⁸Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine tumors and determine its predictive capability for metastasis. Methods: Patients with pathologically diagnosed well-differentiated, non-functional pancreatic neuroendocrine tumors who underwent [⁶⁸Ga]-DOTATOC PET/CT between 2015 and 2021 were included. Medical records and [⁶⁸Ga]-DOTATOC PET/CT indices (maximal and mean standardized uptake values, somatostatin receptor-expressing tumor volume, and total lesion somatostatin receptor expression in pancreatic tumors) were retrospectively reviewed. Correlations between indices were analyzed to determine their collective diagnostic significance. Results: Among 93 patients who were pathologically diagnosed with pancreatic neuroendocrine tumors and underwent [⁶⁸Ga]-DOTATOC PET/CT, 48 with well-differentiated, non-functional pancreatic neuroendocrine tumors without accompanying genetic syndromes were included. The pancreatic neuroendocrine tumors were classified as WHO grade 1 (n = 30, 62.5%) and grade 2 (n = 18, 37.5%), with tumors in 25% of the patients exhibiting initial metastases. A higher incidence of metastasis was observed in larger metabolically active tumors (somatostatin receptor-expressing tumor volume, p < 0.001; total lesion somatostatin receptor expression, p < 0.001). Conclusions: Volumetric parameters derived from [⁶⁸Ga]-DOTATOC PET/CT correlates with initial metastasis in well-differentiated pancreatic neuroendocrine tumors. Full article

Metastases to the breast from non-mammary malignancies are rare, accounting for 0.1–5% of all breast malignancies. Neuroendocrine tumors (NETs) rarely metastasize to the breast. PET-CT somatostatin receptor imaging plays a pivotal role in the staging and follow-up of NETs, leveraging tracers like 68Ga-DOTATOC that bind to somatostatin receptors (SSTRs) expressed on tumor cells. While both primary and metastatic NETs express SSTRs, primary breast tumors may also exhibit an uptake of 68Ga-somatostatin analogs, making the differential diagnosis between primary breast tumors and neuroendocrine metastases challenging. Additionally, imaging characteristics of breast metastases from NETs are poorly documented in the literature, posing a diagnostic challenge that extends to pathology, particularly when in the absence of clinical suspicion. Misdiagnosis in such cases can lead to inappropriate therapeutic interventions. We report the case of a 75-year-old female patient with a history of pancreatic NET who presented to our breast clinic for further evaluation of a breast mass after a PET-CT scan revealed moderate 68Ga-DOTATOC uptake. Multimodality breast examination, including mammography and multiparametric US with B-mode, Color Doppler, Strain Elastography (SE), Shear Wave Elastography (SWE), and contrast-enhanced US (CEUS), was performed. Following a core biopsy, the lesion underwent surgical excision, revealing the diagnosis of NET metastasis. This case highlights a rare instance of neuroendocrine tumor metastasis to the breast, assessed using various ultrasound techniques, with detailed imaging and quantitative analysis. The comprehensive multimodal assessment contributes to the limited body of literature and provides elements for the differential diagnosis of a rare breast lesion that should always be considered in the presence of a known primary NET. Full article

Background: ⁶⁸Ga-DOTATOC PET/CT is a functional imaging modality that has revolutionized the evaluation of well-differentiated neuroendocrine tumors (NETs) by targeting somatostatin receptors. This technique has largely replaced conventional gamma camera imaging with 111In-labeled octreotide due to its superior sensitivity and resolution. While the physiologic distribution, normal variations, and common pitfalls associated with ⁶⁸Ga-DOTATOC imaging are well documented, rare but clinically significant pitfalls can still occur. Methods: We present a case highlighting one such pitfall: focal ⁶⁸Ga-DOTATOC uptake at the cervicothoracic junction, specifically within the stellate ganglia, which mimicked metastatic involvement of a NET. Results: Initially, the uptake was interpreted as a potential right cervical metastasis. To clarify this finding, a follow-up ⁶⁸Ga-DOTATOC PET/CT was performed, which demonstrated no evidence of cervical metastases, thereby confirming the initial uptake as a physiologic variation rather than pathological activity. This case underscores the dynamic variability of ⁶⁸Ga-DOTATOC uptake within the stellate ganglia in the same patient over time. On occasion, the intensity of physiologic uptake in these structures can be pronounced enough to mimic metastatic disease, posing a diagnostic challenge. Conclusions: Awareness of this rare phenomenon is essential to avoid misdiagnosis and unnecessary interventions. Full article

Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a ⁶⁸Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a ⁶⁸Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in ⁶⁸Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. Full article

Introduction and aim: Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. Methods: From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with ¹⁸F-6-fluoro-L-dihydroxyphenylalanine (¹⁸FDOPA, n = 30), ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸FDG, n = 21), or ⁶⁸Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (⁶⁸Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6–12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. Results: The mean age was 61 [extremes, 31–92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7–381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. Conclusion: Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure. Full article

Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (⁶⁸Ga) or fluoro-18 (¹⁸F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [¹⁸F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. Methods: We performed a bibliographic search on three different databases until February 2024 using the following terms: “positron emission tomography”, “PET”, “PET/CT”, “Prostate-specific membrane antigen”, “PSMA”, “non-prostate”, “not prostate cancer”, “solid tumor”, “FDG”, “Fluorodeoxyglucose”, “FAPi”, “FET”, “MET”, “DOPA”, “choline”, “FCH”, “FES”, “DOTATOC”, “DOTANOC”, and “DOTATATE”. Only original articles edited in English with at least 10 patients were included. Results: Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [¹⁸F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. Conclusions: The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [¹⁸F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications. Full article

Background and Objectives: Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension and sweating, but could also be accompanied by symptoms involving multiple organs. Surgery is the gold standard treatment for both PGLs and pheochromocytomas (PHEOs). Material and Methods: We used a computerized endocrine surgery registry to record the demographic and clinical data of 153 patients who underwent surgery for PPGL between 2010 and 2023 at our hospital. Results: Thirteen patients (8.43%) with paragangliomas underwent surgery at our institute. Five patients presented symptomatic syndrome. Preoperative investigations included enhanced abdominal CT (nine patients) and enhanced MRI (seven patients). In cases of suspicious mass, we performed 131I-MIBG scans (two patients) or 68GA-DOTATOC PET-CT scans (11 patients). Laparoscopic approach was used in four cases (30.7%) and abdominal laparotomy in the other nine (69.3%). Biochemical tests were performed on all patients. Conclusions: In this retrospective study, we discuss the multidisciplinary management in our institute of this rare disease, from its challenging diagnosis to the surgical strategy for PGLs. Laparoscopic surgery is the gold standard, but a tailored approach should be adopted for each patient. Full article

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [⁶⁸Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [⁶⁸Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [⁶⁸Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [⁶⁸Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [⁶⁸Ga]Ga-DOTATOC PET/CT. Full article

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. Full article

⁶⁸Ga-DOTATOC PET could be a noninvasive, highly sensitive, and specific technique for the challenging diagnosis of optic nerve sheath meningioma (ONSM). Our objective was to report the use and results of ⁶⁸Ga-DOTATOC PET in suspected ONSM. Twelve subjects who underwent ⁶⁸Ga-DOTATOC PET for suspected ONSM in our department were retrospectively included. Standardised clinical and radiological data were collected. The PET examination results were classified as positive or negative, and lesion standardised uptake values (SUV_max) were recorded. ⁶⁸Ga-DOTATOC PET confirmed positive uptake in six cases (SUV_max > 5), leading to ONSM diagnoses followed by radiation therapy in patients with vision loss. Six ⁶⁸Ga-DOTATOC PET scans were considered negative (SUV_max < 5); these comprised one case of neurosarcoidosis, one cavernous malformation, and four uncertain diagnoses, leading to further investigation. ⁶⁸Ga-DOTATOC PET was helpful in tumour volume delineation before radiation therapy, leading to a decrease in dose exposure. Noninvasive ⁶⁸Ga-DOTATOC PET should be performed before treating nonhistologically proven meningiomas with radiotherapy or stereotactic radiosurgery, particularly in cases of uncertain diagnosis with MRI, which characterises most ONSM cases. PET SUV_max thresholds to distinguish meningioma from nonspecific uptake in other lesions need to be adapted to ONSM. ⁶⁸Ga-DOTATOC PET improves the intraorbital lesion diagnostic approach and therefore impacts therapeutic management. Full article

Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical carcinoid (AC). TC differ from AC not only for its histopathological features but also for its “functional imaging pattern” and prognosis. ACs are more undifferentiated and characterized by higher aggressiveness. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSA) labeled with Gallium-68 (⁶⁸Ga-DOTA-TOC, ⁶⁸Ga-DOTA-NOC, ⁶⁸Ga-DOTA-TATE) has widely replaced conventional imaging with gamma camera using ¹¹¹In- or ^99mTc-labelled compounds and represents now the gold standard for diagnosis and management of NENs. In this setting, as already described for gastro-entero-pancreatic NENs, ¹⁸F-Fluorodeoxiglucose ([¹⁸F]FDG) in addition to ⁶⁸Ga-SSA can play an important role in clinical practice, particularly for ACs that show a more aggressive behavior compared to TCs. The aim of this systematic review is to analyze all original studies collected from the PubMed and Scopus databases regarding PCs in which both ⁶⁸Ga-SSA PET/CT and [¹⁸F]FDG PET/CT were performed in order to evaluate the clinical impact of each imaging modality. The following keywords were used for the research: “¹⁸F, ⁶⁸Ga and (bronchial carcinoid or carcinoid lung)”. A total of 57 papers were found, of which 17 were duplicates, 8 were reviews, 10 were case reports, and 1 was an editorial. Of the remaining 21 papers, 12 were ineligible because they did not focus on PC or did not compare ⁶⁸Ga-SSA and [¹⁸F]FDG. We finally retrieved and analyzed nine papers (245 patients with TCs and 110 patients with ACs), and the results highlight the importance of the combined use of ⁶⁸Ga-SSA and [¹⁸F]FDG PET/CT for the correct management of these neoplasms. Full article