Somatostatin Receptor Imaging Research Articles

Presacral Neuroendocrine Neoplasms: A Multi-site Review of Surgical Outcomes.

Presacral neuroendocrine neoplasms (PNENs) are rare tumors, with limited data on management and outcomes. A retrospective review of institutional medical records was conducted to identify all patients with PNENs between 2008 and 2022. Data collection included demographics, symptoms, imaging, surgical approaches, pathology, complications, and long-term outcomes. Twelve patients were identified; two-thirds were female, averaging 44.8years of age, and, for the most part, presenting with back pain, constipation, and abdominal discomfort. Preoperative imaging included computed tomography scans and magnetic resonance images, with somatostatin receptor imaging and biopsies being common. Half of the patients had metastatic disease on presentation. Surgical approach varied, with anterior, posterior, and combined techniques used, often involving muscle transection and coccygectomy. Short-term complications affected one-quarter of patients. Pathologically, PNENs were mainly well-differentiated grade 2 tumors with positive synaptophysin and chromogranin A. Associated anomalies were common, with tail-gut cysts prevalent. Mean tumor diameter was 6.3cm. Four patients received long-term adjuvant therapy. Disease progression necessitated additional interventions, including surgery and various chemotherapy regimens. Skeletal, liver, thyroid, lung, and pancreatic metastases occurred during follow-up, with no mortality reported. Kaplan-Meier analysis showed a 5-year local recurrence rate of 23.8%, disease progression rate of 14.3%, and de novo metastases rate of 30%. The study underscores the complex management of PNENs and emphasizes the need for multicenter research to better understand and manage these tumors. It provides valuable insights into surgical outcomes, recurrence rates, and overall survival, guiding future treatment strategies for PNEN patients.

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.

Somatostatin receptor imaging of thyroid tissue and differentiated thyroid cancer using gallium-68-labeled radiotracers-a review of clinical studies.

The rise in thyroid cancer incidence, especially papillary thyroid cancer (PTC), has underscored the need for improved diagnostic methods and management strategies. Herein, we aim to comprehensively review the evolving landscape in thyroid cancer diagnosis and the potential utility of Gallium-68 (Ga-68) based somatostatin receptor imaging. We reviewed the clinical studies involving Ga-68 based radiotracers by looking at the following literature databases -PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE. We employed a detailed search strategy with the following search terms; PubMed: ("gallium Ga 68 dotatate" [Supplementary Concept]) AND ("Thyroid Gland"[Mesh] OR "Thyroid Nodule"[Mesh] OR "Thyroid Neoplasms"[Mesh]), Embase ("gallium 68" AND "Thyroid Disease"), Web of Science: ("Gallium 68 and Thyroid"). A comparison between Ga-68 DOTATATE and Ga-68 DOTANOC showed similar sensitivities but a higher uptake for Ga-68 DOTATATE. Studies comparing Ga-68-based SSTR PET with FDG PET highlighted the potential advantages of both approaches, with Ga-68-based SSTR PET being more specific in certain cases. Ga-68-based somatostatin receptor imaging displays clinical utility in RAI-R DTC, offering valuable insight into detecting skeletal lymph node metastases. Notably, it shows potential as a primary imaging tool, potentially augmenting the role of FDG PET. However, SSTR PET imaging's efficacy in distinguishing benign from malignant thyroid nodules varies, with a complex interplay of factors influencing its specificity, indicating its value as an adjunct to existing methods, warranting further research for a refined role in thyroid cancer management. Although study variations exist, Ga-based somatostatin receptor imaging holds potential as a complementary tool alongside diagnostic methods in thyroid cancer diagnosis, with particular relevance to RAI-R DTC. In carefully selected patients demonstrating the presence of Ga-68 DOTATATE avid lesions, further exploration, and investigation into the potential utilization of Lu177 DOTATATE are warranted.

Somatostatin Receptor Imaging with [18F]FET-βAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.

There is a clinical need for 18F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [68Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [18F]fluoroethyl-triazole-[Tyr3]-octreotate ([18F]FET-βAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [18F]FET-βAG-TOCA PET/CT compared with [68Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [18F]FET-βAG-TOCA and [68Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6-180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [18F]FET-βAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [18F]FET-βAG-TOCA PET/CT, and [68Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [18F]FET-βAG-TOCA was significantly lower than that of [68Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [18F]FET-βAG-TOCA was not inferior to [68Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.

Design, Preclinical Evaluation, and Clinical Translation of 68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma.

Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68Ga, its dual-receptor-binding affinity was evaluated invitro and invivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18F-FDG. Results: 68Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68Ga-FAPI-LM3 was significantly higher than that of 68Ga-FAPI-46 and 68Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both invitro and invivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68Ga-FAPI and 68Ga-DOTA-LM3. This study highlights the clinical feasibility of 68Ga-FAPI-LM3 PET/CT for NPC imaging.

Determinants of the uptake of the uncinate process of pancreas in 68Ga-DOTATOC PET/CT: a retrospective study.

an increased uptake of the uncinate process of pancreas (UPP) has been described in about one-third of somatostatin receptor imaging procedures and may hinder image interpretation. The determinants of this uptake are however poorly understood. The aim of this study was to investigate the impact of cold somatostatin analogues (cSA) on UPP 68Ga-DOTATOC uptake. Age and diabetic status were also studied. all adult patients who performed a 68Ga-DOTATOC PET/CT in our center between May 2021 and April 2023 were retrospectively screened. For each one, UPP uptake was visually assessed and measured using SUVmax. Clinical data including cSA medication, age and diabetic status were collected. Univariate and multivariate analyses were conducted using logistic regression. SUVmax comparisons were conducted using a Mann-Whitney Wilcoxon test. 82 patients were included. UPP uptake was significantly lower in patients treated with cSA (OR 0.27, p = 0.015 in multivariate analysis), with a lower SUVmax (4.97 vs. 8.81, p = 0.001). No significant result was found regarding diabetic status or age. cold somatostatin analog treatment decreased the physiological UPP uptake in 68Ga-DOTATOC PET/CT. This effect could be used to reduce interpretation errors in this location.

Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site.

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

Somatostatin Receptor Imaging in Mice with Difference Positive Rate of SSTR2.

Imaging with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 was performed to analyze differences among the three probes, and to analyze the correlation between the image and pathology parameters. Tumor bearing mice with different positive rates of somatostatin receptor II (SSTR2) were established with HEK293-SSTR2 and HEK293 cells, and imaging was performed on the same mouse with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 at 20, 60 and 120 min. The image parameters were obtained, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), standard deviation of SUVmean (SD), tumor volume and coefficient of variation (CoV). Immunohistochemistry of the tumor was performed after imaging to obtain positive rate of SSTR2. Statistical analysis was performed to analyze the differences among the three imaging techniques and the correlations between the relative imaging parameter and immunohistochemistry (IHC). The SUVmax of [18F]AlF-NOTA-JR11 at 20 and 60 min was higher than that of [68Ga]Ga-DOTA-TATE (P=0.0015, 0.0035) and [68Ga]Ga-DOTA-JR11 (P=0.033, 0.019), and no significant difference was found in the other groups (P>0.05). There was a significant positive correlation between the positive rate and SUVmean of tumors with three tracers (P<0.05). However, a significant negative correlation between the positive rate and CoV was found only in the [68Ga]Ga-DOTA-TATE group at 60 min and 120 min (P=0.048, 0.026). [18F]AlF-NOTA-JR11 is more suitable for SSTR imaging within an hour than other two tracers. SUVmean of whole tumor can become an indicator for evaluating the positive rate of IHC, and the higher SUVmean of three tracers means a higher positive rate. However, the CoV is not applicable to the two antagonist tracers for evaluating the positive rate.

Somatostatin Receptor Expression in Lung Neuroendocrine Tumors: An Analysis of DOTATATE PET Scans.

Somatostatin receptor (SSTR) expression in metastatic lung neuroendocrine tumors (NETs) has not been well characterized using PET imaging. Understanding the degree and uniformity of SSTR expression is important to establish the role of SSTR-targeted treatments in lung NETs. Methods: A retrospective institutional review of patients with metastatic lung NETs who underwent DOTATATE PET imaging from March 2017 to February 2023 was performed. Results: In total, 48 patients with metastatic lung NETs who underwent 68Ga- or 64Cu-DOTATATE PET imaging were identified. Four had completely negative SSTR expression, and 10 had very weak expression (less than in a normal liver). Among the remaining 34 patients, 21 had uniformly positive DOTATATE PET scans, and 13 had heterogeneous expression. Only 44% had uniformly positive receptor expression, identifying them as candidates for peptide receptor radionuclide therapy. Conclusion: Most metastatic lung NETs lack uniform SSTR expression and are thus suboptimal candidates for SSTR-targeted therapy. SSTR imaging in lung NETs should be evaluated carefully for uniformity of expression.

Effects of somatostatin analogs on uptake of radiolabeled somatostatin analogs on imaging: a systematic review and meta-analysis.

The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients. The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 vs. 7.62±2.12, P=0.001) and spleen (25.74±7.14 vs. 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique. Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.

Nuclear Imaging Modalities in the Diagnosis and Management of Thyroid Cancer.

In this review we have brought forward various nuclear imaging modalities used in the diagnosis, staging, and management of thyroid cancer. Thyroid cancer is the most common endocrine malignancy, accounting for approximately 3% of all new cancer diagnoses. Nuclear imaging plays an important role in the evaluation of thyroid cancer, and the use of radioiodine imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the management of this disease. Radioiodine imaging involves the use of Iodine-123 [I-123] or Iodine-131 [I-131] to evaluate thyroid function and detect thyroid cancer. I-123 is a gamma-emitting isotope that is used in thyroid imaging to evaluate thyroid function and detect thyroid nodules. I-131 is a beta-emitting isotope that is used for the treatment of thyroid cancer. Radioiodine imaging is used to detect the presence of thyroid nodules and evaluate thyroid function. FDG imaging is a PET imaging modality that is used to evaluate the metabolic activity of thyroid cancer cells. FDG is a glucose analogue that is taken up by cells that are metabolically active, such as cancer cells. FDG PET/CT can detect primary thyroid cancer and metastatic disease, including lymph nodes and distant metastases. FDG PET/CT is also used to monitor treatment response and detect the recurrence of thyroid cancer. Somatostatin receptor imaging involves the use of radiolabeled somatostatin analogues to detect neuroendocrine tumors, including thyroid cancer. Radiolabeled somatostatin analogues, such as Indium-111 octreotide or Gallium-68 DOTATATE, are administered to the patient, and a gamma camera is used to detect areas of uptake. Somatostatin receptor imaging is highly sensitive and specific for the detection of metastatic thyroid cancer. Methods: A comprehensive search of relevant literature was done using online databases of PubMed, Embase, and Cochrane Library using the keywords "thyroid cancer," "nuclear imaging," "radioiodine imaging," "FDG PET/CT," and "somatostatin receptor imaging" to identify relevant studies to be included in this review. Conclusion: Nuclear imaging plays an important role in the diagnosis, staging, and management of thyroid cancer. The use of radioiodine imaging, thyroglobulin imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the evaluation of thyroid cancer. With further research and development, nuclear imaging techniques have the potential to improve the diagnosis and management of thyroid cancer and other endocrine malignancies.

Quantitative uptake in 99m Tc-EDDA/HYNIC-TOC somatostatin receptor imaging - the effect of long-acting release somatostatin analogue therapy.

Withdrawal of long-acting release somatostatin analogue (LAR-SSA) treatment before somatostatin receptor imaging is based on empirical reasoning that it may block uptake at receptor sites. This study aims to quantify differences in uptake of 99m Tc-EDDA/HYNIC-TOC between patients receiving LAR-SSA and those who were not. Quantification of 177 patients (55 on LAR-SSA) imaged with 99m Tc-EDDA/HYNIC-TOC was performed, with analysis of pathological tissue and organs with physiological uptake using thresholded volumes of interest. Standardised uptake values (SUVs) and tumour/background (T/B) ratios were calculated and compared between the two patient groups. SUVs were significantly lower for physiological organ uptake for patients on LAR-SSA (e.g. spleen: SUV max 13.3 ± 5.9 versus 33.9 ± 9.0, P  < 0.001); there was no significant difference for sites of pathological uptake (e.g. nodal metastases: SUV max 19.2 ± 13.0 versus 17.4 ± 11.5, P  = 0.552) apart from bone metastases (SUV max 14.1 ± 13.5 versus 7.7 ± 8.0, P  = 0.017) where it was significantly higher. LAR-SSA has an effect only on physiological organ uptake of 99m Tc-EDDA/HYNIC-TOC, reducing uptake. It has no significant effect on pathological uptake for most sites of primary and metastatic disease. This should be taken into account if making quantitative measurements, calculating T/B ratios or assigning Krenning Scores. There is the potential for improved dosimetric results in Peptide Receptor Radionuclide Therapy by maintaining patients on LAR-SSA.

Case report: Peptide receptor radioligand therapy in metastatic pediatric neuroendocrine tumors

Neuroendocrine tumors (NETs) are not commonly diagnosed in children. Metastatic NETs tend to have poor outcomes, and this is seen in adult and pediatric populations. The role of somatostatin receptor imaging using [68Ga]Ga-DOTA-TATE for imaging and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE in children is currently not well established. The guidelines for treating pediatric neuroendocrine tumors are still lacking. Extensive trials have been conducted in adult patients and have demonstrated improved survival in metastatic NETs with PRRT using [177Lu]Lu-DOTA-TATE. We present two pediatric patients with metastatic NETs who were imaged with [68Ga]Ga-DOTA-TATE PET/CT and treated with [177Lu]Lu-DOTA-TATE therapy.

Imaging surveillance in multiple endocrine neoplasia type 1: Ten years of experience with somatostatin receptor positron emission tomography.

Guidelines for multiple endocrine neoplasia type 1 (MEN1) recommend intensive imaging surveillance without specifying a superior regimen, including the role of somatostatin receptor imaging (SRI) with positron emission tomography (PET). The primary outcomes were to: (1) Assess change in treatment of duodenal-pancreatic neuroendocrine neoplasms (DP-NENs), bronchopulmonary NENs, and thymic tumors attributed to use of SRI PET/computed tomography (CT) and (2) estimate radiation from imaging and risk of cancer death attributed to imaging radiation. This was a retrospective single center study, including all MEN1 patients, who had had at least one SRI PET/CT. A total of 60 patients, median age 42 (range 21-54) years, median follow-up 6 (range 1-10) years were included. Of 470 cross sectional scans (MRI, CT, SRI PET/CT), 209 were SRI PET/CT. The additional information from SRI PET had implications in 1/14 surgical interventions and 2/12 medical interventions. The estimated median radiation dose per patient was 104 (range 51-468) mSv of which PET contributed with 13 (range 5-55) mSv and CT with 91 mSv (range 46-413 mSv), corresponding to an estimated increased median risk of cancer death of 0.5% during 6 years follow-up. SRI PET had a significant impact on 3/26 decisions to intervene in 60 MEN1 patients followed for a median of 6 years with SRI PET/CT as the most frequently used modality. The surveillance program showed a high radiation dose. Multi-modality imaging strategies designed to minimize radiation exposure should be considered. Based on our findings, SRI-PET combined with CT cannot be recommended for routine surveillance in MEN1 patients.

In-Vivo Somatostatin-Receptor Expression in Small Cell Lung Cancer as a Prognostic Image Biomarker and Therapeutic Target.

Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). A total of 67 patients (26 females; age, 41-80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = -0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients.

Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors.

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

Somatostatin Receptor Targeted PET-CT and Its Role in the Management and Theranostics of Gastroenteropancreatic Neuroendocrine Neoplasms

Somatostatin receptor (SSTR) agonist-based Positron Emission Tomography-Computed Tomography (PET-CT) imaging is nowadays the mainstay for the assessment and diagnostic imaging of neuroendocrine neoplasms (NEN), especially in well-differentiated neuroendocrine tumors (NET) (World Health Organization (WHO) grade I and II). Major clinical indications for SSTR imaging are primary staging and metastatic workup, especially (a) before surgery, (b) detection of unknown primary in metastatic NET, (c) patient selection for theranostics and appropriate therapy, especially peptide receptor radionuclide therapy (PRRT), while less major indications include treatment response evaluation on and disease prognostication. Dual tracer PET-CT imaging using SSTR targeted PET tracers, viz. [68Ga]Ga-DOTA-Tyr3-Octreotate (DOTA-TATE) and [68Ga]Ga-DOTA-NaI3-Octreotide (DOTA-NOC), and fluorodeoxyglucose (FDG), have recently gained widespread acceptance for better assessment of whole-body tumor biology compared to single-site histopathology, in terms of being non-invasive and the ability to assess inter- and intra-tumoral heterogeneity on a global scale. FDG uptake has been identified as independent adverse risk factor in various studies. Recently, somatostatin receptor antagonists have been shown to be more sensitive and specific in detecting the disease. The aim of this review article is to summarize the clinical importance of SSTR-based imaging in the clinical management of neuroendocrine and related tumors.

Association of guideline adherence in diagnosis and treatment of pancreatic neuroendocrine tumors with survival.

e16241 Background: Clinical guidelines and their adherence are important instruments to ensure quality in diagnosis and treatment, especially when treating rare diseases like pancreatic neuroendocrine tumors (PanNET). However, data on guideline adherence and its impact on outcome in PanNET is limited. Methods: Cases of PanNET according to 2017 WHO definition at our university hospital between 2010 and 2019 were retrospectively identified. Adherence to ENETS guideline 2007/2012 and the German S2k guideline was evaluated among four categories (diagnostics: chromogranin A (CgA) testing, somatostatin receptor imaging, discussion in an interdisciplinary tumor board; pathology: reporting of grading, Ki67 and synaptophysin expression; surgical treatment; systemic treatment including aftercare). Guideline adherence within these categories was valued with one point per fulfilled criterion and a final score between 0-8 points was calculated. Data was analyzed using Student’s t-test, Chi-square test and Spearman’s correlation coefficient test. Results were considered significant at α = 0.05. Results: Overall, 115 patients (47% female) with a diagnosis of PanNET were identified. Mean age was 61 (±13.5) years. Mean overall survival (OS) was 45 months, mean recurrence free survival (RFS) was 47 months. During the study period 21 patients (18%) had died, 6 patients (5%) were lost-to-follow-up and 11 patients (10%) had a recurrent disease after initially curative resection. 24 patients (21%) presented with metastatic disease upon diagnosis. Guideline adherence concerning pathology reports (97%) as well as systemic (91%) and surgical treatment (75%) was high, while complete adherence in diagnostic modalities was low (5%). However, the latter was mainly driven by lack of CgA testing (31%), and somatostatin receptor imaging (11%) not being performed on initial diagnosis, but in most cases during follow-up. Subsequently, complete guideline adherence (8/8) across all categories was rare (3%). However, a higher overall score was associated with survival (p = 0.032, V = 0.321). Long term survivors had a higher mean overall adherence score (5.6 vs. 6.1; p = 0.05). In addition, the composite score of surgical and systemic therapy was significantly correlated with RFS (ρ = 0.254, p = 0.016). Conclusions: The quality in diagnosis and treatment of PanNET in our cohort was high. These are the first data to demonstrate a positive impact of guideline adherence on survival and RFS in PanNET.

Detection of acute myocarditis by ECG-triggered PET imaging of somatostatin receptors compared to cardiac magnetic resonance: preliminary results

AbstractSomatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered digital-PET imaging of somatostatin receptors (68Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting. MethodsFourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered 68Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology 68Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients. ResultsAn increased myocardial 68Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial 68Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months. ConclusionThese preliminary results suggest that 68Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.

Prospective evaluation of the utility of concurrent 18F-FDG PET/CT and 68Ga-DOTA-TOC imaging in gastroenteropancreatic neuroendocrine neoplasms (GEPNENs): The PETNET study.

4022 Background: Somatostatin receptor imaging (SRI) is a standard of care for patients with GEPNETs. The additional value of concurrent 18F-FDG PET/CT (FDG PET) remains unclear. We reviewed a prospective functional imaging study to determine the utility of FDG PET in GEPNENs. Methods: PETNET is a prospective study in British Columbia, Canada, which provides all 68Ga-DOTA-TOC (DOTA PET) imaging in the province. Every patient receives a DOTA PET scan and an FDG PET within 30 days. PETNET enrolls all patients with an indication for SRI. Scans are ordered per treating physician discretion at any point in the disease course. This abstract focuses on the WD-GEPNEN population. Only the first dual functional imaging scans were analyzed and FDG was interpreted qualitatively (positive/negative). Results: From 04/2017-01/2023, 375 patients with NEN were enrolled, 165 (44%) with metastatic GEPNENs. Baseline characteristics are described. Median time between scans was 4 days (IQR 1-11). The proportion of patients with positive FDG PET at baseline increased with WHO grade. For patients with well differentiated G1 to G3 GEPNENs (N=161), overall survival was significantly lower with a positive FDG PET (HR: 4.22; 95%CI 1.61-11.02 p=0.001). FDG remained prognostic when G3 tumors were excluded (N=148) (HR 3.52; 95%CI 1.32-9.42 p= 0.007). When analyzing dual tracer PET imaging, patients with DOTA+/FDG- had reduced risk of dying in comparison with DOTA+/FDG+ (HR:0.26; 95%CI 0.09-0.67 p=0.01). After multivariate analysis, FDG positivity remained independently associated with reduced survival (HR 2.87; 95%CI 1.06-7.75 p=0.04) when controlling for grade of tumor and age. Conclusions: In this prospective cohort of metastatic GEPNENs, a positive FDG PET was significantly associated with reduced overall survival. These results provide additional evidence to support dual tracer functional imaging use in metastatic well differentiated GEPNEN’s. [Table: see text]