Search Results (75)

Meningiomas arise from the meningeal layers covering the central nervous system structures. Although most are benign, meningiomas can still cause neurological morbidity due to the mass effect and compression of the surrounding parenchyma. The prognosis also depends on several factors such as growth pattern or location. Morphological imaging approaches, such as MRI and CT, that emphasize intracranial calcifications, vascular patterns, or invasion of major vessels act as the basis of the diagnosis; PET/CT imaging is a valuable diagnostic tool for assessing somatostatin receptor activity in tumors. It enables the visualization and quantification of somatostatin receptor expression, providing insights into tumor biology, receptor status, and potential therapeutic targets. Aside from radiosurgery and neurosurgical intervention, peptide receptor radionuclide therapy (PRRT) has also shown promising results. Somatostatin receptors 1 and 2 are nearly universally expressed in meningioma tissue. This characteristic is increasingly exploited to identify patients eligible for adjuvant therapy using DOTA-conjugated somatostatin receptor-targeting peptides PET. In the treatment of relapsed/refractory meningiomas, PRRT is increasingly considered a safe and effective therapeutic option. It is often supported by artificial intelligence strategies for dose optimization and side-effect monitoring. The objective of this study is to evaluate the safety and benefits of these strategies based on the latest findings. 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

Gallium-labeled positron emission tomography (PET) probes targeting activated fibroblasts or somatostatin receptor expression are frequently used for varying applications in oncology. With the widespread availability of ⁶⁸Ge/⁶⁸Ga generators and cold kits, ⁶⁸Ga tracers have become a main tool in molecular imaging. These tracers, such as [⁶⁸Ga]Ga-DOTA-TATE, [⁶⁸Ga]Ga-FAPI, and [⁶⁸Ga]Ga-pentixafor, allow targeted imaging of the key pathological processes, including inflammation, fibrosis, and necrosis. This review highlights their potential in conditions like myocardial infarction, cardiac sarcoidosis, myocarditis, and other cardiomyopathies. Clinical and preclinical studies underscore their utility in visualizing active disease processes, predicting outcomes, and guiding therapeutic strategies. However, challenges remain, including the need for standardization, larger clinical trials, and integration into routine practice. These advancements position ⁶⁸Ga-based PET as a promising modality for enhancing diagnostic precision and personalized treatment in cardiovascular disease. Full article

Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against these tumors. Methods: A search for the existing literature on systemic therapies for meningiomas was performed on PubMed and a search for presently accruing clinical trials was performed on ClinicalTrials.gov. Results: Systemic treatments, including chemotherapy, somatostatin analogs, anti-hormone therapy, and anti-angiogenic therapy, have been extensively studied with marginal success. Targeted therapies are actively being studied for the treatment of meningiomas, including focal adhesion kinase (FAK), sonic hedgehog signaling pathway, phosphoinositide-3-kinase (PI3K), and cyclin-dependent kinases (CDK) inhibitors. These driver mutations are present only in a subset of meningiomas. In stark contrast, somatostatin receptor 2 (SSTR2) is ubiquitously expressed in meningiomas and was formerly targeted with somatostatin analogs with modest success. Theranostic SSTR2-targeting via [⁶⁸Ga]DOTATATE for PET imaging and β-emitting [¹⁷⁷Lu]DOTATATE for the treatment of meningiomas are currently under active investigation. Conclusions: A nuanced approach is needed for the treatment of refractory meningiomas. Targeted therapies show promise. Full article

Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change. Full article

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC). Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset. ⁶⁷Ga-DOTATATE uptake was measured, ¹⁷⁷Lu-DOTATATE cytotoxicity was assessed, and ⁶⁸Ga-DOTATATE tumor targeting was evaluated in HCC animal models and a patient via PET/CT imaging. Results: SSTR2 expression was confirmed in HCC cell lines and clinical samples. Radioligand uptake studies demonstrated SSTR2-mediated ⁶⁷Ga-DOTATATE uptake. ¹⁷⁷Lu-DOTATATE treatment reduced cell proliferation and enhanced the anti-tumor efficacy of the multikinase inhibitor sorafenib. ⁶⁸Ga-DOTATATE PET/CT scans successfully identified tumors in HCC animal models and spinal metastases in a patient with HCC. Conclusion: These findings provide evidence that SSTR2-based theranostics could have significant implications for the detection and treatment of HCC. Full article

Objective: Currently, ⁶⁸Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor uptake and prolonged tumor retention time. To enhance the uptake and retention of tracers in NETs, our goal is to design a ⁶⁸Ga-labeled heterodimer for optimizing pharmacokinetics and assess whether this form is more efficacious than its monomeric equivalents. Methods: Using the somatostatin analog TATE and quinoline-based compound FAPI-46 as raw materials, we designed and synthesized ⁶⁸Ga-labeled TATE-46. The labeling efficiency and stability were verified by Radio-HPLC. The receptor binding properties and tumor targeting were examined both in vitro and in vivo by using NCI-H727 (SSTR2/FAP, positive) and Mc38 (SSTR2/FAP, negative) cell lines and tumor-bearing mouse models. Preclinical evaluation was performed through cell uptake, pharmacokinetics, Micro PET, and biodistribution studies, and the results were compared with [⁶⁸Ga]Ga-DOTA-TATE and [⁶⁸Ga]Ga -FAPI-46. Immunohistochemistry and HE staining were performed on tumor tissues from tumor-bearing mice for further validation. Results: [⁶⁸Ga]Ga-TATE-46 showed comparable SSTR2 and FAP targeting ability to monomeric TATE and FAPI-46 in cell uptake and PET imaging studies. [⁶⁸Ga]Ga-TATE-46 exhibited significantly higher uptake in NCI-H727 (SSTR2/FAP, positive) tumors compared to [⁶⁸Ga]Ga-DOTA-TATE (p < 0.001) and [⁶⁸Ga]Ga-FAPI-46 (p < 0.001). No increased uptake of [⁶⁸Ga]Ga-TATE-46 was observed in MC38 tumors (SSTR2/FAP, negative). Additionally, excess DOTA-TATE and/or unlabeled FAPI-46 significantly blocked the uptake of [⁶⁸Ga]Ga-TATE-46 in NCI-H727 tumors (p < 0.001), confirming its dual-receptor targeting characteristics. The ex vivo biodistribution, immunofluorescence and immunohistochemistry results were in line with the in vivo imaging findings. Conclusion: Compared with ⁶⁸Ga-labeled FAPI-46 and DOTA-TATE mono-specific tracers, the dual-target tracer [⁶⁸Ga]Ga-TATE-46 improves tumor uptake, extends tumor retention, and enhances pharmacokinetics. It is an effective probe for non-invasive detection of tumors expressing FAP and SSTR2, and it is worth further studying its application in the expression of sstr2 and FAP-related tumors. 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

Background: Parathyroid tumors are classified as parathyroid neuroendocrine neoplasia (NEN) by the IARC-WHO classification. These tumors can occur with NENs from other sites, which often require total-body [68Ga]-DOTA-peptides PET/CT. This study aimed to assess the utility of [68Ga]-DOTA-peptide PET/CT in imaging parathyroid NENs and to evaluate the underlying mechanisms. Methods: Fifty patients with primary hyperparathyroidism (PHPT) and parathyroid NENs histologically confirmed as parathyroid adenomas (PAs) were included. PET/CT with [68Ga]-DOTA-peptide was performed in 16 patients with localized PAs, including 10 with MEN1 syndrome. Somatostatin receptor types 2 and 5 (SST2 and SST5) staining was performed on PAs from 48 patients. Somatostatin analogs (SSA) were prescribed in four patients with MEN 1 syndrome and 1 with persistent acromegaly, all with PAs and PHPT. The therapy effects on calcium and parathyroid hormone (iPTH) were evaluated. Results: [68Ga]-DOTA-peptide PET/CT detected 20 PAs with high radiopharmaceutical uptake. SST2 expression was negative on PA cell membranes in all cases and positive on endothelium in 39 (81%) PAs. Membrane SST5 expression was positive in 25 (52%) PAs and endothelial was positive in 40 (83%). Serum calcium levels decreased in patients on SSA therapy, while iPTH did not. Conclusions: PET/CT with [68Ga]-DOTA-peptides can detect parathyroid NENs. The incidental detection of high [68Ga]-DOTA-peptide uptake in the parathyroid region during whole-body PET/CT may prompt biochemical evaluation for PHPT. We suggest that endothelial SST expression mediates high radiopharmaceutical uptake by PAs and that SSA treatment can reduce hypercalcemia in PHPT patients. Full article

We present the case of a 60-year-old male with recurrent atypical meningioma in the right parietal lobe, previously treated with surgery and radiation therapy. Magnetic resonance imaging (MRI) performed 5 years after radiation therapy suggested a possible recurrence. A somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) scan with Gallium-68 DOTATATE was performed to confirm this suspicion. SR-PET/CT confirmed the presence of recurrent meningioma, showing a novel “rosary sign” with multiple adjacent areas of focal tracer uptake along the resection margins of the previous surgical site in the right parietal region. This novel imaging pattern improved diagnostic accuracy by detailing disease extent and identifying additional lesions not visible via MRI. Given the failure of prior treatments and high SR expression, peptide receptor radionuclide therapy (PRRT) was proposed as a therapeutic option for the patient. Full article

Non-somatostatin receptor expressing hypovascular insulinomas can be challenging to prove through imaging. This case highlights the utility of a structured approach to molecular imaging in patients with confirmed endogenous hyperinsulinemia. A 54-year-old woman was admitted because of a sudden loss of consciousness. Her relative reported that she complained of dizziness, intense sweating, blurry vision, and upper extremity tingling before becoming unresponsive for 20 min, after which the patient had little recollection of the event. She experienced similar episodes of shorter duration, trouble recalling everyday events, and unintentional weight gain of over 10 kg during the previous two years. Abdominal magnetic resonance imaging (MRI) and multidetector computerized tomography (MDCT) were unremarkable. Selective arterial calcium stimulation significantly increased hepatic venous insulin concentrations when the superior mesenteric and gastroduodenal arteries were stimulated. Technetium-99m (99mTc) octreotide single-photon emission computed tomography (SPECT) did not localize the lesion. Gallium-68 DOTA-Exendin-4 PET/CT acquisition was performed. A single intense 2 cm hyperperfused pancreatic lesion was located anteriorly in the head of the pancreas. Earlier targeted PET/CT imaging and recognition of significant neuropsychiatric symptoms attributable to the patient’s hypoglycemic state might have accelerated the resolution of her condition and obviated the need for unnecessary testing. 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

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. ¹⁸F-FDG PET/CT has been widely used and has demonstrated prognostic value, but ¹⁸F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice. Full article

The overexpression of somatostatin receptor type 2 (SSTR2) is a property of various tumor types. Hybrid imaging utilizing [⁶⁸Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) may improve the differentiation between tumor and healthy tissue. We conducted an experimental study on 47 anonymized patient cases including 30 meningiomas, 12 PitNET and 5 SBPGL. Four independent observers were instructed to contour the macroscopic tumor volume on planning MRI and then reassess their volumes with the additional information from DOTA-PET/CT. The conformity between observers and reference volumes was assessed. In total, 46 cases (97.9%) were DOTA-avid and included in the final analysis. In eight cases, PET/CT additional tumor volume was identified that was not detected by MRI; these PET/CT findings were potentially critical for the treatment plan in four cases. For meningiomas, the interobserver and observer to reference volume conformity indices were higher with PET/CT. For PitNET, the volumes had higher conformity between observers with MRI. With regard to SBGDL, no significant trend towards conformity with the addition of PET/CT information was observed. DOTA PET/CT supports accurate tumor recognition in meningioma and PitNET and is recommended in SSTR2-expressing tumors planned for treatment with highly conformal radiation. Full article

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [⁶⁸Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [¹⁷⁷Lu]LuDOTA-LM3 and [²²⁵Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest–abdomen–pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity. Full article