SSTR Expression

The presented study confirmed similar properties of Ln-complexes, suggesting that lutetium-177 can be replaced by other radiolanthanides, most probably without affecting the tissue distribution profile of the resultant radiopharmaceuticals. On the other hand, the different radii of the lanthanide ions affected their uptake and resorption mechanisms in liver and bones when injected in uncomplexed form.

Multidisciplinary consultation recommended initiation of systemic chemotherapy with cisplatin and etoposide. This case underscores the aggressive nature and poor prognosis associated with malignant insulinomas, particularly those with high proliferative indices. It highlights the complexities of managing refractory hypoglycemia in the context of widespread metastatic disease and emphasizes the urgent need for effective therapeutic strategies to improve patient outcomes.

68Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic EBV-positive nonkeratinizing nasopharyngeal carcinoma and delineating primary tumor boundary.

The longest ECS remission and CMR continues at >17 years. PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.

Our exploratory analysis provides preliminary results showing that imaging indices of inter- and intra-tumor heterogeneity from pretreatment PET/CT images may potentially predict treatment efficacy in NET patients undergoing [177Lu]Lu-DOTA-TATE therapy. However, prospective evaluation in a larger cohort is needed to further assess whether a comprehensive characterization of tumor heterogeneity within a patient can help guide treatment decisions.

Neuroblastomas may be misdiagnosed as phaeochromocytomas given the ability to secrete catecholamines and similarities in radiological appearance. Differentiating neuroblastomas from phaeochromocytomas and paragangliomas (PPGL) is critical, but clinically difficult. Genomics are central for management; diagnosing ALK-positive neuroblastoma triggers consideration of ALK-targeted therapy, which is not relevant for PPGL. A critical eye is required for the accurate diagnosis and management of malignant adrenal incidentalomas.

Volumetric parameters of pretreatment 68[Ga]Ga-DOTA-TATE PET/CT may be useful in prediction of the response to SSA (used in monotherapy as a first-line therapy) in patients with NET.

Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.

However, postoperative histological studies suggested that the intracellular domain of SSTRs were highly expressed, while the extracellular domain may be mutated. We present a rare case of insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression.

However, there is no published case of mucinous adenocarcinoma with 68Ga-DOTATATE uptake. We present a unique case of metastatic mucinous adenocarcinoma of unknown origin on 68Ga-DOTATATE PET/CT.

Postoperatively, patient improved clinically and recovered from hypophosphatemia completely. A distinct focal uptake in a 68Ga- DOTATATE PET-CT in a patient with tumor-induced osteomalacia needs extensive workup and high degree of suspicion to rule out mesenchymal tumor at nonconventional location as seen in the present case.

Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS...Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs...This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68Ga-DOTATATE PET/CT.

Subsequently EN lesions of the lower extremities resolved. We present a rare case of GEP-NET-associated EN, that improved with surgical tumor cytoreduction and hormone therapy.

&lsqb;61Cu]Cu-NODAGA-TOC is superior to &lsqb;61Cu]Cu-DOTA-TOC in vivo. The use of the chelator NODAGA allows quantitative labeling with copper-61 at room temperature and enables the straightforward use of a kit formulation for simple manufacturing in medical centers.

In 27 hospitalized patients with CD at Osaka University Hospital, Osaka, Japan, associations between corticotroph tumor diameter, the response of ACTH and cortisol to differential diagnostic tests for CD (CRH, desmopressin [DDAVP], and high-dose dexamethasone suppression test [HDDST]), the ACTH/cortisol index, and the SSTR5 immunoreactive score were retrospectively investigated. Tests for differential diagnosis of CD, the ACTH/cortisol index, and the corticotroph tumor diameter have the potential for identifying SSTR5 expression in corticotroph tumors. These parameters may reflect the biological characteristics of corticotroph tumors.

Our data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.

However, other malignancies such as lymphomas (both Hodgkin and non-Hodgkin) also have expression of somatostatin receptors, albeit to a lesser degree compared with the neuroendocrine tumors, and thus can be positive on a 68Ga-DOTATATE PET/CT. We describe an atypical presentation of an aggressive large B-cell lymphoma mimicking a metastatic neuroendocrine tumor at initial presentation with high somatostatin receptor expression demonstrated on the 68Ga-DOTATATE PET/CT and a rapidly progressing course on the subsequent 18F-FDG PET/CT.

Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines.

PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET)...Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

Moreover, there was focal 18F-SiTATE uptake in the left caudate and corresponding contrast enhancement due to postischemic blood-brain barrier disruption and reactive SSTR expression. Therefore, increased cortical or subcortical SSTR PET signal may be related to ischemic changes even in the subacute stage after initial stroke.

However, limited cases have been reported demonstrating 68Ga-DOTATATE uptake in the metastases of RCC. Herein, we describe a unique case of RCC with multiple atypical metastatic sites, emphasizing the usefulness of 68Ga-DOTATATE PET/CT in the evaluation and follow-up of patients with RCC.

Radiologists should be aware of the advantages of somatostatin receptor PET/MRI in evaluation of head and neck tumors as well as the potential pitfalls of this approach so that they can accurately advise clinicians and better interpret these studies.

Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue lutetium-177 octreotate (177Lu-DOTATATE), which was well tolerated...The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient's case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes, which will be important to advance treatment strategies based on MRT for children with high-risk NB.

P=N/A, N=940, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Here, we discuss a case of TIO in a patient initially presenting with symptoms of inflammatory spondyloarthritis. SSTR positron emission imaging using 68Ga-DOTATATE was central in diagnosing and localizing the primary tumor.

P1/2, N=30, Recruiting, The First Affiliated Hospital of Xiamen University | Phase classification: P1 --> P1/2 | N=20 --> 30

Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings.

[225Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET.

Here, we present a case of a NET with wandering, large, heterogeneous masses in the abdominopelvic regions that were identified using dual-tracer PET/CT. After the administration of temozolomide chemotherapy in a combined chemotherapy-peptide receptor radionuclide therapy approach, we observed an upregulation in the expression of somatostatin receptor in the abdominopelvic masses.

This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration-approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.

The fixed relative threshold method was found to be the most effective and easily applicable method to measure SRETV on pretreatment 68Ga-DOTATATE PET/CT to predict prognosis in GEPNET patients. WB-SRETV45% (cutoff value of 11.8 cm3) and WB-SRETV60% (cutoff value of 6.3 cm3) were found to be the strongest predictors of prognosis in GEPNET patients.

SSTR PET is mandated to determine eligibility for peptide receptor radionuclide therapy. Here, the role of imaging to aid management of NEN is reviewed.

P1, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases.

Knowledge and consideration of these factors in adjusting &lsqb;177Lu]Lu-oxodotreotide treatment regimen could help prevent or reduce the severity of these toxicities. Further studies are still warranted to refine these results and improve treatment management.

P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. In patients treated with &lsqb;177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.

After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.

PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.

In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering β-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2)...However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.

P2, N=20, Recruiting, Jules Bordet Institute | Trial completion date: Sep 2023 --> Jun 2024 | Trial primary completion date: Sep 2023 --> Jun 2024