Overexpression Of Somatostatin Receptors Research Articles

ESR Essentials: role of PET/CT in neuroendocrine tumors-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Neuroendocrine neoplasms (NEN) originate from the secretory cells of the neuroendocrine system, with the majority arising in the gastrointestinal tract and pancreas. Given the heterogeneity in the biological behavior and morphological differentiation of these tumors, advanced imaging techniques are crucial for supporting the suspected diagnosis, accurate staging, and monitoring therapy. As most well-differentiated NEN demonstrate overexpression of somatostatin receptors (SSR) on the cell surface, SSR-directed PET/CT is considered the reference standard for imaging of this particular entity. SSR-PET/CT should be the imaging method of choice in every NEN G1 or G2 and considered for re-staging after both potentially curative and non-curative surgeries. The extent of SSR expression is also crucial for determining a patient's eligibility for peptide receptor radionuclide therapy (PRRT). 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). PET/CT is a central component of the multidisciplinary management of NEN. Variable follow-up intervals are recommended, considering that tumors with higher proliferation rates or advanced metastatic disease require more frequent assessments. The combination with other imaging modalities, like MRI, complements SSR-PET/CT, further enhancing overall diagnostic accuracy. KEY POINTS: Somatostatin receptor-PET/CT (SSR-PET/CT) is the guideline-recommended reference standard for imaging well-differentiated neuroendocrine tumors (NET). SSR-PET/CT should be the diagnostic imaging of choice for staging and post-therapy re-staging of grade 1 or 2 NET (G1 or G2). Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

Hybrid Somatostatin Receptor PET/MRI of the Head and Neck.

Hybrid PET/MRI has the potential to transform neuro-oncologic imaging, particularly in diagnosis and treatment planning of somatostatin receptor-expressing tumors of the head and neck. Hybrid PET/MRI combines high-resolution MRI with functional information from PET, providing precise anatomic information and overcoming difficulties in localization inherent to PET alone. There is a range of tumors in the head and neck that overexpress somatostatin receptors and are therefore amenable to evaluation with somatostatin receptor PET/MRI. These include meningiomas, paragangliomas, olfactory neuroblastomas, pituitary neuroendocrine tumors, middle ear neuroendocrine tumors, and medullary thyroid carcinomas. The combination of PET and MRI is superior to either modality alone and can address several unique diagnostic challenges associated with these lesions. The authors discuss the superior capabilities of somatostatin receptor PET/MRI, including improved lesion localization, more sensitive demonstration of disease extent, enhanced surveillance, optimized radiation therapy planning, and accurate prediction of response to somatostatin analog therapy. Although there are only a few dedicated PET/MRI units available in clinical practice, commercial software is now available that can automatically fuse PET/CT data with recently acquired MRI data, increasing the availability of this approach. 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. ©RSNA, 2024 See the invited commentary by Shatzkes and Strauss in this issue.

Phosphaturic mesenchymal tumor demonstrated by 68Ga-DOTATATE PET/CT in a patient: a case report

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by abnormally high levels of fibroblast growth factor 23 (FGF-23), most commonly produced and secreted by small phosphaturic mesenchymal tumors (PMT). These tumors can show various anatomic locations throughout soft tissue and bone. The presence of the tumor itself rarely causes symptoms. Nonspecific symptoms such as muscle weakness and musculoskeletal pain are related to the developing hypophosphatemia and osteomalacia as a secondary effect of the increased circulating levels of FGF-23. Therefore, as the initial presentation can mimic a wide range of metabolic or inflammatory diseases, proper diagnosis is often delayed. Localization of the tumor is crucial, as its complete surgical resection is the only curative treatment. Whole-body functional imaging targeting the overexpression of somatostatin receptors (SSTR) on the surface of the PMT cells, is a highly specific and sensitive imaging method to detect the primary tumor site. 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.

Nuclear medicine approaches in the diagnosis and treatment of neuroendocrine neoplasms

Despite, or perhaps because of the rarity of neuroendocrine neoplasms, the diagnosis and treatment of these malignancies is of particular importance. Nuclear medicine can make an important contribution to this challenge. It offers the most sensitive and specific imaging of these tumor entities and can be helpful in treatment due to the radiotherapeutic drugs that have recently been approved. This theragnostic (fusion of therapeutic and diagnostic) concept is based on the frequent overexpression of somatostatin receptors on neuroendocrine tumor cells.Using diagnostic and therapeutic pharmaceuticals based on analogues from somatostatin, most applications from the nuclear medicine are successful, an additional therapeutic method is SIRT, also known as TARE, in which the hypervascularization of NEN-metastases is used as a therapeutic target.

68 Ga-DOTATOC Pictorial Essay of Various Recurrent Meningiomas Rejected for Treatment With 177 Lu-DOTATATE : Is There a Place for Another Theranostic Examination?

We report the cases of 4 patients treated for recurrent meningiomas of various grades. Pretreatment 68 Ga-DOTATOC PET/CT was performed prior to screening for vectorized internal radiotherapy with 177 Lu-DOTATATE or prior external radiotherapy to aid contouring. None of these patients had sufficient uptake to be eligible for 177 Lu-DOTATATE or reliable contouring. Most recurrences were grades II and III, suggesting a loss of physiological somatostatin receptor overexpression in these tumors. Therefore, the benefit of treatment with 177 Lu-DOTATATE in the current indication is questionable. In the absence of a validated systemic treatment, and considering a few case reports, treatment with 177 Lu-PSMA could be investigated as an additional vectorized internal radiotherapy option.

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[177Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

Meeting Notes of the Taiwan Neuroendocrine Tumor Society &amp; Taiwan Society of Nuclear Medicine Joint Conference - Peptide Receptor Radionuclide Therapy Targeting for Gastroenteropancreatic Neuroendocrine Tumors: Basic Principles and State-of-the-art Clinical Practice

Abstract Objective: The current study aimed to investigate the basic principles and clinical applications, including the selection of proper candidates, follow-up strategies, and radiation protection issues relating to peptide receptor radionuclide therapy (PRRT). Data Sources and Study Selection: We searched various scientific databases using specific keywords. Results: Due to the overexpression of somatostatin receptors in neuroendocrine tumors (NETs), PRRT is currently considered an important therapeutic modality for the management of NETs. Conclusion: PRRT incorporates the systemic administration of a tumor-targeting radiolabeled peptide to patients with tumors, allowing for more precise delivery of radiation doses to tumor sites while sparing normal tissues.

Comparison of 68Ga-DOTATATE Positron Emmited Tomography/Computed Tomography and Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases from Well-Differentiated Neuroendocrine Tumors.

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET (p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.

Lutétium-177 en Médecine Nucléaire

The most developed clinical fields using lutetium 177 initially concerned neuroendocrine tumors overexpressing somatostatin receptors. Secondary prostate lesions expressing prostate-specific membrane antigen (PSMA) represent a potentially significant new field of application. This article proposes a synthesis concerning this radionuclide, both γ and β- emitter, which is of medical interest for theranostic applications.

68 Ga-DOTATATE PET/CT in the Initial Diagnosis of Patients With Clinical, Imaging, and/or Biochemical Suspicion of a Neuroendocrine Tumor.

The aim of this study was to assess the yield of somatostatin receptor PET in patients with clinical, imaging, and/or biochemical suspicion of a neuroendocrine tumor (NET). This analysis includes patients referred for the initial diagnosis of an unconfirmed NET, as part of a prospective, single-arm registry study (NCT03873870) assessing the utility of 68 Ga-DOTATATE PET/CT in the management of NETs. Inclusion criteria to this cohort consisted of elevated biomarkers and/or clinical presentation suspicious for a NET, with negative conventional cross-sectional imaging, or presence of a lesion suspicious for a NET on conventional imaging, not amenable for biopsy. Patients with histological confirmation of a NET were excluded. There were 220 patients included between April 2019 and March 2022 with a mean age ± SD of 59.5 ± 16.1 years with biochemical, morphological, and/or clinical suspicion of a NET. Overall, 132/220 patients (60%) had a positive 68 Ga-DOTATATE PET/CT. 68 Ga-DOTATATE PET/CT confirmed a type 2 somatostatin receptor overexpressing tumor in 123/171 (71.9%) of patients with a radiographically suspicious abnormality. The positivity rate for pancreatic, small bowel/mesenteric, adrenal, and other sites was 78/96 (81.2%), 38/57 (66.7%), 7/7 (100%), and 1/11 (9.1%), respectively. 68 Ga-DOTATATE PET/CT was positive in 9/49 (18.4%) of those with a biochemical and/or clinical suspicion of a NET. 68 Ga-DOTATATE PET/CT is positive in nearly 3 of 4 patients with morphological suspicion of a NET, with the highest yield in those with pancreatic and small bowel or mesenteric masses, and in approximately 1 of 6 patients with biochemical and/or clinical suspicion of a NET.

Severe gastroenteritis as presentation of a neuroendocrine tumor of pancreas

Pancreatic neuroendocrine tumors (PanNETs) are a very rare entity, corresponding to 1-2% of all pancreatic neoplasms, although incidence and prevalence are rising. According to hormonal production, they can be functional or nonfunctional, leading to a subset of symptoms. A 45-year-old man, came to our emergency department complaining of vomiting and profuse non-bloody diarrhea for a week, with asthenia and no improvement with medication. He presented with diminished muscular strength and severe electrolytic changes with electrocardiographic repercussion. Patient was admitted to our intensive care unit (ICU) for hypovolemic and distributive shock due to a severe gastroenteritis. Further research studies were carried out which have shown a nodular structure of 5x4cm in the pancreas tail on computed tomography scan. A biopsy was made, and a histopathological exam revealed a pancreatic well differentiated neuroendocrine tumor. Hormonal analysis showed an elevation on vasoactive intestinal polypeptide (VIP). On 68Ga-DOTA-NOC PET/CT, there were 2 nodular lesions with anomalous overexpression of somatostatin receptors, one in the pancreatic tail near splenic hilum and another in the pancreatic head. Patient underwent a total pancreaticoduodenectomy with en bloc splenectomy. Postoperative period was uneventful. Mostly, this kind of pancreatic neuroendocrine tumors are indolent, but till 39% can have an aggressive course, so they have variable prognosis.

RYZ101 (Ac-225 DOTATATE) Opportunity beyond Gastroenteropancreatic Neuroendocrine Tumors: Preclinical Efficacy in Small-Cell Lung Cancer.

Overexpression of somatostatin receptors (SSTR), particularly SSTR2, is found in gastroenteropancreatic neuroendocrine tumors (GEP-NET), and subsets of other solid tumors such as small-cell lung cancer (SCLC). SCLC accounts for approximately 13% to 15% of lung cancer and lacks effective therapeutic options. IHC analysis indicates that up to 50% of SCLC tumors are SSTR2-positive, with a substantial subset showing high and homogenous expression. Peptide receptor radionuclide therapy with radiolabeled somatostatin analogue, Lu-177 DOTATATE, has been approved for GEP-NETs. Different strategies aimed at improving outcomes, such as the use of alpha-emitting radioisotopes, are currently being investigated. RYZ101 (Ac-225 DOTATATE) is comprised of the alpha-emitting radioisotope actinium-225, chemical chelator DOTA, and octreotate (TATE), a somatostatin analogue. In the cell-based competitive radioligand binding assay, RAYZ-10001-La (lanthanum surrogate for RYZ101) showed high binding affinity (Ki = 0.057 nmol/L) to human SSTR2 and >600-fold selectivity against other SSTR subtypes. RAYZ-10001-La exhibited efficient internalization to SSTR2-positive cells. In multiple SSTR2-expressing SCLC xenograft models, single-dose intravenous RYZ101 3 μCi (0.111 MBq) or 4 μCi (0.148 MBq) significantly inhibited tumor growth, with deeper responses, including sustained regression, observed in the models with higher SSTR2 levels. The antitumor effect was further enhanced when RYZ101 was combined with carboplatin and etoposide at clinically relevant doses. In summary, RYZ101 is a highly potent, alpha-emitting radiopharmaceutical agent, and preclinical data demonstrate the potential of RYZ101 for the treatment of patients with SSTR-positive cancers.

68Ga-DOTA-peptide PET/CT for radiotherapy planning and evaluating treatment response in the management of meningiomas.

Meningiomas overexpress somatostatin receptors (SSTR). PET imaging with SSTR ligands such as 68Ga-DOTA-peptide has recently shown high diagnostic accuracy in identification of meningiomas due to lack of normal bone and brain activity. PET-derived parameters, especially gross tumour volume (GTV) delineation improves inter-observer variability and appears to be particularly promising for RT planning. The potential strength of 68Ga-DOTA in the ongoing assessment of treatment response and disease progression in meningioma, particularly in the post-surgical and post-radiation settings is encouraging. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and 177Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of 177Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. 177Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study

BackgroundPeptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282).ResultsThe sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity.ConclusionThis study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.

Technetium-99m labelled somatostatin analogue myocardial uptake in subacute and “old” myocardial infarction: initial experience

Background. It has been shown that prognosis following acute myocardial infarction (MI) strongly correlates with intensity of inflammatory reactions in response to myocardial injury. Thereby diagnostic methods for myocardial post-infarction inflammation (PII) monitoring are needed. Scintigraphy with somatostatin receptor targeted radiotracers has prospects for PII imaging, but its clinical value is poorly studied.Methods. Six patients with ST-segment elevation anterior myocardial infarction (STEMI) were examined by chest SPECT/СT with 99mTc-Tektrotyd and rest myocardial perfusion scintigraphy (MPS) at subacute and remote (8 th month) period of the disease. Parameters of both scintigraphic methods were estimated.Results. In subacute stage of MI myocardial perfusion defects were revealed in all 6 patients (mean SRS 11.83 ± 8.89), 99mTc-Tektrotyd uptake in myocardium was revealed in 3 of 6 patients. At remote period intense uptake of 99mTc-Tektrotyd was found only in 1 patient. This uptake was more spread and clears, comparing with accumulation in subacute stage of AMI.Conclusion. Myocardium scintigraphy with 99mTc-Tektrotyd allows identifying overexpression of somatostatin receptors in areas of recent and old myocardium infarction. In some patients the radiopharmaceutical uptake may expands to a remote period of the disease. Further larger studies and histological validation of scintigraphic results are needed.

Ga-68 DOTATATE PET/CT in the Evaluation of Paragangliomas and Other Indeterminate Lesions in the Head and Neck.

Paragangliomas (PGLs) are rare neuroendocrine tumors with imaging features that can overlap with other entities. This study hypothesizes that given overexpression of somatostatin receptor (SSTR) 2, PGLs can be differentiated on Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) from other benign or malignant lesions. Ninety-six patients with known tumors of the head and neck who underwent Ga-68 DOTATATE PET/CT from May 2017 to December 2021 were retrospectively reviewed from a single institution. Of these, 43 patients had histopathological confirmation and 66 positive lesions were discovered on PET/CT. For each lesion, the SUV max, the SUV lesion to liver ratio, and the SUV lesion to spleen ratio were analyzed. PGLs (n = 37) showed the most intense uptake, and the mean of SUVmax was 69.3 (range 3.7-225.9). Metastatic PGL and metastasis from other neuroendocrine tumors (n = 13) demonstrated intermediate uptake, the mean of SUVmax was 15.16 (range 2.3-40.3). Meningiomas (n = 3) had intermediate uptake, and the mean of SUVmax was 12.37 (range 2.5-19.4). One patient with esthesioneuroblastoma had 5 lesions in the head and neck, and the mean of SUVmax was 18.9 (range 6.9-49.4). Schwannomas (n = 4) had very low uptake, and the mean of SUVmax was 1.75 (range 1.1-2.2). Other rare cases with low uptake included 1 each of osteosarcoma, acinic cell carcinoma, ectopic thyroid tissue, and plasmacytoma, and the mean of SUVmax was 4.75 (range 2.3-6.1). Ga-68 DOTATATE PET/CT can be a useful adjunct in differentiating tumors in the head and neck. PGLs demonstrate the highest uptake. Meningioma, esthesioneuroblastoma, and neuroendocrine tumor metastasis have intermediate uptake. Schwannomas and other rare tumors exhibit low uptake.

Investigational PET tracers in neuro-oncology-What's on the horizon? A report of the PET/RANO group.

Many studies in patients with brain tumors evaluating innovative PET tracers have been published in recent years, and the initial results are promising. Here, the Response Assessment in Neuro-Oncology (RANO) PET working group provides an overview of the literature on novel investigational PET tracers for brain tumor patients. Furthermore, newer indications of more established PET tracers for the evaluation of glucose metabolism, amino acid transport, hypoxia, cell proliferation, and others are also discussed. Based on the preliminary findings, these novel investigational PET tracers should be further evaluated considering their promising potential. In particular, novel PET probes for imaging of translocator protein and somatostatin receptor overexpression as well as for immune system reactions appear to be of additional clinical value for tumor delineation and therapy monitoring. Progress in developing these radiotracers may contribute to improving brain tumor diagnostics and advancing clinical translational research.

Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors

BackgroundNeuroendocrine tumors (NETs) overexpress somatostatin receptors (SSTRs).MethodsWe developed a second-generation, ligand-based, anti-SSTR chimeric antigen receptor (CAR) incorporating the somatostatin analog octreotide in its extracellular moiety.ResultsAnti-SSTR CAR T cells exerted antitumor...

Prognostic Value of the Largest Lesion Size for Progression-Free Survival in Patients with NET Undergoing Salvage PRRT with [177Lu]Lu-DOTATOC.

Simple SummaryPeptide receptor radionuclide therapy (PRRT) using radionuclide-labeled somatostatin analogues is based on the overexpression of somatostatin receptors on neuroendocrine tumors and is shown to have a good safety profile and efficacy in different types of metastatic neuroendocrine tumors. As this therapy is usually not curative, most patients experience disease progression after initial PRRT. In these cases, retreatment with PRRT, also called salvage PRRT, can be a treatment option, but little is known about the efficacy and possible risk factors. In this retrospective study that included 32 patients, we found that the size of the largest lesion is a significant predictor of disease progression after salvage PRRT. This risk factor is easy to obtain and can help identify patients who may benefit from intensified follow-up strategies.(1) Background: retreatment with radionuclide-labeled somatostatin analogues following disease progression after initial treatment cycles is often referred to as salvage peptide receptor radionuclide therapy (salvage PRRT). Salvage PRRT is shown to have a favorable safety profile in patients with metastatic neuroendocrine tumors (NETs), but numerous questions about the efficacy and prognostic or predictive factors remain to be answered. The purpose of this study was to evaluate two parameters that have shown prognostic significance in progression-free survival (PFS) in initial PRRT treatment, namely the size of the largest lesion (LLS) and the De Ritis ratio (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)), as prognostic factors in the context of salvage PRRT. In addition, the PFS after initial PRRT was evaluated as a predictor of the PFS following salvage PRRT. (2) Methods: retrospective, monocentric analysis in 32 patients with NETs (gastroenteropancreatic, 23; unknown primary, 7; kidney, 1; lung, 1) and progression after initial PRRT undergoing retreatment with [177Lu]Lu-DOTATOC. The prognostic values of LLS, the De Ritis ratio, and PFS after initial treatment cycles regarding PFS following salvage PRRT were evaluated with univariable and multivariable Cox regression. PFS was defined as the time from treatment start until tumor progression according to RECIST 1.1 criteria, death from any cause or start of a new treatment due to progression of cancer-related symptoms (namely carcinoid syndrome). (3) Results: progression after salvage PRRT was observed in 29 of 32 patients with median PFS of 10.8 months (95% confidence interval (CI), 8.0–15.9 months). A higher LLS (hazard ratio (HR): 1.03; p = 0.002) and a higher De Ritis ratio (HR: 2.64; p = 0.047) were associated with shorter PFS after salvage PRRT in univariable Cox regression. PFS after initial PRRT was not associated with PFS following salvage PRRT. In multivariable Cox regression, only LLS remained a significant predictor. (4) Conclusions: the size of the largest lesion is easy to obtain and might help identify patients at risk of early disease progression after salvage PRRT. Validation is required.