Endocrinology application of molecular imaging: current role of PET/CT.

BACKGROUND: In recent years, nuclear medicine imaging methods have proven to be of paramount importance in a wide variety of diseases, particularly in oncology, where they are crucial for assessing the extent of disease when conventional methods fall short. Moreover, nuclear imaging modalities are able to better characterize lesions using target agents related to specific pathways (e.g. glucose metabolism, cellular proliferation, amino acid transport, lipid metabolism, specific receptor ligands). The clinical presentation of endocrine diseases encompasses a broad spectrum of sign and symptoms. Moreover, endocrine tumors show varying degrees of aggressiveness from well differentiated and indolent to highly aggressive cancers, respectively. RATIONALE: With the application of new medicinal radio-compounds and increasingly advanced tomographic imaging technology, the utility of Positron Emission Tomography/Computed Tomography (PET/CT) in the field of endocrine diseases is expanding. AIM: This review aims to analyze and summarize the primary indications of PET/CT, providing a practical approach for clinicians. A comprehensive literature search on PubMed was conducted to provide an updated overview of the available evidence regarding the use of PET/CT in endocrinology. Within this review, we will discuss the applications of PET/CT, compare different radiopharmaceuticals and highlight the uptake mechanism, excluding neuroendocrine carcinomas from discussion. CONCLUSIONS: PET/CT is a valuable tool in diagnosing and managing endocrine disorders due to its capacity to furnish both functional and anatomical information, facilitate early lesion detection, guide treatment decisions, and monitor treatment response. Its non-invasive nature and precision make it an integral component of modern endocrine healthcare. This review aims to provide physicians with a clear perspective on the role of PET/CT imaging, discussing its emerging opportunities and appropriateness of use in endocrinological diseases.

Comparative Analysis of Diagnostic Efficacy in Primary Hyperparathyroidism: A Comparison Analysis of 11C-Choline PET/CT, Neck Ultrasonography, 99mTc-MIBI Dual-Phase Planar Scintigraphy, and 99mTc-MIBI SPECT/CT Imaging.

Objective: To compare the diagnostic efficacy of 11C-choline PET/CT, neck ultrasonography, 99mTc-MIBI dual-phase planar scintigraphy, and 99mTc-MIBI SPECT/CT imaging in the diagnosis of primary hyperparathyroidism (PHPT). Methods: We conducted a retrospective analysis of 32 patients with PHPT who visited the Nuclear Medicine Department of Jilin University China-Japan Union Hospital between January 2019 and December 2022. All patients underwent 11C-choline PET/CT, neck ultrasonography, 99mTc-MIBI dual-phase planar scintigraphy, and 99mTc-MIBI SPECT/CT examinations within two months before surgery. Sensitivity, specificity, positive predictive value, and negative predictive value of each imaging study were compared using postoperative pathology and follow-up results. Diagnostic efficacy was further analyzed using ROC curve analysis. Factors influencing on 99mTc-MIBI imaging were also investigated. Results: A total of 35 lesions were resected in the 32 patients. The diagnostic sensitivity of 11C-choline PET/CT, neck ultrasonography, 99mTc-MIBI dual-phase planar scintigraphy, and 99mTc-MIBI SPECT/CT was 88.2%, 52.9%, 58.8%, and 67.6%, respectively. Specificity was 96.8%, 95.7%, 96.8%, and 95.7%, respectively. Positive predictive values were 90.9%, 81.8%, 86.9%, and 85.2%, respectively, and negative predictive values were 95.7%, 84.9%, 86.7%, and 89.1%, respectively. The areas under the ROC curve (AUC) were 0.925, 0.743, 0.778, and 0.817, respectively. Among them, 11C-choline PET/CT had higher sensitivity and AUC than other imaging studies (p<0.05), while specificity, positive predictive value, and negative predictive value were similar (p>0.05). The positive group in 99mTc-MIBI SPECT/CT imaging had significantly larger lesion diameters than the negative group (P<0.05), while preoperative blood calcium and PTH showed no statistical differences (P>0.05). Conclusion: 11C-choline PET/CT demonstrates superior preoperative diagnostic efficacy for PHPT compared to neck ultrasonography, 99mTc-MIBI dual-phase planar scintigraphy, and 99mTc-MIBI SPECT/CT. Lesion size may be the primary factor affecting the sensitivity of 99mTc-MIBI imaging.

Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline.

Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[11C]methionine and [11C]choline, was performed, using a microfluidic cassette and an iMiDEVTM module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[11C]methionine and [11C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [11C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[11C]methionine and >60% for [11C]choline (n = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[11C]methionine and [11C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields.

[11C]Choline PET/CT in a Patient with Prostate Cancer Biochemical Recurrence Showing Two Suspicious Findings in the Breast and Liver.

A 79-year-old man with prostate cancer (PCa) was referred to our center to perform a [11C]Choline PET/CT for biochemical recurrence. Positron emission tomography/computed tomography (PET/CT) scan detected PCa recurrence in the prostate gland and several pelvic and abdominal lymph nodes. Two abnormal uptakes were also identified in the right breast and in the liver, respectively. Breast histological findings turned out to be gynecomastia, while the liver lesion resulted in a benign perfusion anomaly at follow-up magnetic resonance imaging (MRI). Although incidental findings were benign in this case, it is important to always investigate abnormal uptakes of [11C]Choline, as it could be an expression of further metastases or synchronous malignancies such as breast cancer and hepatocellular carcinoma.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

An 18F-MD-PSMA (Multi-dentate PMSA Imaging Agent) PET/CT in Prostate Cancer Relapse: Results of a Retrospective Trial.

PURPOSE: This study aimed to evaluate the performance of 18F-MD-PSMA PET/CT in patients previously treated for prostate cancer by either surgery or therapy, but later relapsed biochemically. METHODS: This retrospective study enrolled 213 patients in sequence previously treated for prostate cancer by either surgery or therapy, but later PSA relapsed. A total of 191 of these 213 patients were included in this analysis. All patients were biochemically relapsed after radical prostatectomy or therapy, had 18F-MD-PSMA PET/CT scan within 1 week, and were off hormonal therapy at the time of the scans. The new tracer was compared directly with 11C-choline in sensitivity. RESULTS: In 3 patients, a side-by-side comparison between 18F-MD-PSMA and 11C-choline was performed, and it was found that the former was about 3 times more sensitive than the latter. The analysis of PET imaging using 18F-MD-PSMA in 191 relapsed patients showed that less than 10% of patients showed the disease limited in the prostate. Among the remote lesions, the number in decreasing order was bone, followed by lymph nodes and other organs. The maximal SUV in lesions in each patient followed an exponential decay, with SUV inclined to the lower end. The Gleason score measured at the diagnosis showed no correlation with the average number of lesions in each patient, the average maximal SUV values among this cohort of patients, and the PSA values measured at the time of PET imaging. The number of lesions observed in each patient has no correlation with the PSA value measured at the time of PET imaging. When PSA value was measured as an independent biomarker at the time of PET imaging, the positivity of PET imaging using 18F-MD-PSMA increased along with an increase in PSA value, but with exceptions where PSMA expression was low or negative. From the PET imaging of this radioligand, the majority of patients showed oligo-metastasis, favoring using local therapy to manage the disease. CONCLUSION: An 18F-MD-PSMA as a radioligand was found to be superior to 11C-choline in the setting of patients with biochemical relapse after previous treatment. Its PET imaging results matched those of established PSMA radioligands, but its chemical structure was found to have added features to conjugate with other functional molecules, such as those with therapeutic properties. This radioligand lays the foundation for our further work.

Effectiveness of 11C-choline PET/CT in prostate cancer surveillance.

AIM: Our aim was to analyse the performance of [11C]choline PET/CT in prostate cancer (PCa) surveillance, especially in patients with prostate specific antigen (PSA) < 1 ng/mL. MATERIAL AND METHODS: Three hundred and twenty-nine [11C]choline PET/CT examinations from 191 patients (68.2 ±â€¯7.2 years) submitted for PCa surveillance or biochemical recurrence were retrospectively evaluated. PSA at study was 13.0 ±â€¯84.2 ng/mL. Main initial treatment was radical prostatectomy (RP) in 81 patients, and other treatments (radiotherapy, chemotherapy, hormonotherapy) in 110. PET/CT was acquired 20' after injection of 555-740 MBq of [11C]choline. Minimum follow-up was 12 months. RESULTS: Two hundred and nineteen (66.6%) out of the 329 PET/CT examinations were positive. The percentage of positive examinations was significantly higher in patients with other initial treatment than RP compared to patients with RP (85.6% vs. 43.6%, respectively). One hundred and thirty PET/CT (59.4%) showed local recurrence, 48 (21.9%) distant recurrence, and 41 (18.7%) local plus distant recurrence. Initial therapeutic approach was changed in 139 cases (63.5%). In the subgroup of 81 [11C]choline PET/CT scans performed with PSA < 1 ng/mL, 23 (28.4%) showed a positive result. Initial therapeutic approach was changed in 9 (11.1%). Three (4.8%) out of 63 patients died as per PCa. CONCLUSION: [11C]choline PET/CT demonstrated its effectiveness in PCa surveillance and restaging, even in patients with serum PSA < 1 ng/mL. The diagnostic performance was different depending on the initial treatment, been higher in patients with non-surgical treatment.

Questionable value of [99mTc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound.

PURPOSE: A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [99mTc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. METHODS: A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. RESULTS: From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13-93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [99mTc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [11C]-methionine or [11C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24-33.56). CONCLUSION: [11C]-Methionine or [11C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.

Evaluation of 11 C-choline positron emission tomography/computed tomography for determining treatment response in castration-resistant prostate cancer patients.

OBJECTIVE: The utility of 11 C-choline positron emission tomography/computed tomography for determining treatment response as compared with prostate-specific antigen response and prognosis prediction in castration-resistant prostate cancer patients was investigated. METHODS: Eighty-four 11 C-choline-positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium-223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration-resistant prostate cancer patients were retrospectively examined. Prostate-specific antigen values were determined before and after treatment. Using the Kaplan-Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate-specific antigen response and prognostic impact was evaluated. RESULTS: Pretreatment 11 C-choline-positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate-specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was -48.9%, -55.0% (range -92.4% to -19.1%), -4.2% (-33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate-specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer-specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11 C-choline-positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer-specific survival showed significant stratification (P < 0.001). CONCLUSIONS: 11 C-choline-positron emission tomography/computed tomography may reflect castration-resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations.

18F-FDG Versus Non-FDG PET Tracers in Multiple Myeloma.

Multiple myeloma (MM) accounts for 0.9% of cancer diagnoses, and incidence and mortality rate have increased in previous years. 18F-fluorodeoxyglucose (FDG) PET-computed tomography (CT) is an established modality for MM evaluation. MR imaging is helpful where 18F-FDG PET-CT is lacking. To standardize PET reporting, methods like Italian Myeloma Criteria for PET Use and Deauville criteria have been studied. Tracers like 11C-acetate and 11C-choline/18F-fluoromethylcholine (FCH) have shown higher sensitivity and detected more focal lesions and diffuse involvement than 18F-FDG PET-CT. 18F-FCH showed higher maximum standardized uptake value than 18FDG. 11C-methionine appears to be the best radiopharmaceutical, apart from 18F-FDG, for evaluating MM.

Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

Atypical Metastases in the Abdomen and Pelvis From Biochemically Recurrent Prostate Cancer: 11C-Choline PET/CT With Multimodality Correlation.

PET with targeted radiotracers has become integral to mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with 11C-choline is part of the National Comprehensive Cancer Network and European Association of Urology guidelines for evaluation of BCR. With advances in PET technology, increasing use of targeted radiotracers, and improved survival of patients with BCR because of novel therapeutics, atypical sites of metastases are being increasingly encountered, challenging the conventional view that prostate cancer rarely metastasizes beyond bones or lymph nodes. The purpose of this article is to describe such atypical metastases in the abdomen and pelvis on 11C-choline PET (including metastases to the liver, pancreas, genital tract, urinary tract, peritoneum, abdominal wall, and perineural spread) and to present multimodality imaging features and relevant imaging pitfalls. Given atypical metastases' inconsistent relationship with the serum PSA level and the nonspecific presenting symptoms, atypical metastases are often first detected on imaging. Awareness of their imaging features is important because their detection affects clinical management, patient counseling, prognosis, and clinical trial eligibility. Such awareness is particularly critical because the role of radiologists in the imaging and management of BCR will continue to increase given the expanding regulatory approvals of other targeted and theranostic radiotracers.

Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends.

Accurate primary staging is the cornerstone in all malignancies. Different morphological imaging modalities are employed in the evaluation of prostate cancer (PCa). Regardless of all developments in imaging, invasive histopathologic evaluation is still the standard method for the detection and staging of the primary PCa. Magnetic resonance imaging (MRI) and computed tomography (CT) play crucial roles; however, functional imaging provides additional valuable information, and it is gaining ever-growing acceptance in the management of PCa. Targeted imaging with different radiotracers has remarkably evolved in the past two decades. [111In]In-capromab pendetide scintigraphy was a new approach in the management of PCa. Afterwards, positron emission tomography (PET) tracers such as [11C/18F]choline and [11C]acetate were developed. Nevertheless, none found a role in the primary staging. By introduction of the highly sensitive small molecule prostate-specific membrane antigen (PSMA) PET/CT, as well as recent developments in MRI and hybrid PET/MRI systems, non-invasive staging of PCa is being contemplated. Several studies investigated the role of these sophisticated modalities in the primary staging of PCa, showing promising results. Here, we recapitulate the role of targeted functional imaging. We briefly mention the most popular radiotracers, their diagnostic accuracy in the primary staging of PCa, and impact on patient management.

Prostate cancer: Molecular imaging and MRI.

The role of molecular imaging in initial evaluation of men with presumed or established diagnosis of prostate cancer and work up of biochemical recurrence and metastatic disease is rapidly evolving due to superior diagnostic performance compared to anatomic imaging. However, variable tumor biology and expression of transmembrane proteins or metabolic alterations poses a challenge. We review the evidence and controversies with emphasis on emerging PET radiopharmaceuticals and experience on clinical utility of PET/CT and PET/MRI in diagnosis and management of prostate cancer.

Utility of radiomic zones for risk classification and clinical outcome predictions using supervised machine learning during simultaneous 11 C-choline PET/MRI acquisition in prostate cancer patients.

PURPOSE: In most radiomic studies related to cancer research, the traditional tumor-centric view has predominated. In this retrospective study, we go beyond the single-tumor region and investigate the utility of proposed radiomic zones for risk classification and clinical outcome predictions using radiomic features extracted from 11 C-choline positron emission tomography (PET) imaging and supervised machine learning in prostate tumors. MATERIALS AND METHODS: Seventy-seven prostate tumors were selected and delineated. The prostate organ was divided into three radiomic zones, with zone-1 being the metabolic tumor zone, zone-2 the proximal peripheral tumor zone, and zone-3 the extended peripheral tumor zone. LIFEx was used for PET-radiomic feature extraction. Risk groups were created using Gleason scores (GS), prostate-specific antigen (PSA) levels, clinical TNM staging, and progression-free survival (PFS). Random forest (RF) and AdaBoost advanced machine learning algorithms were used for supervised machine learning. Accuracy, positive predictive value, area under the receiver operating characteristic curve (AreaROC), and other metrics were calculated for comparisons of predictive performance between zones. RESULTS: For the GS risk classification group, the accuracies of risk classification predictions were 71%, 71%, and 67% using RF and 65%, 64%, and 63% using AdaBoost for zones -1, -2, and -3, respectively. For the PSA group, the accuracies of risk classification predictions were 74%, 65%, and 64% using RF and 76%, 66%, and 67% using AdaBoost for zones -1, -2, and -3, respectively. For the TNM group, the accuracies of risk classification predictions were 68%, 76%, and 78% using RF and 66%, 75%, and 80% using AdaBoost for zones -1, -2, and -3, respectively. For the PFS group, the accuracies of clinical outcome predictions were 77%, 75%, and 83% using RF and 77%, 74%, and 83% using AdaBoost in zones -1, -2, and -3, respectively. CONCLUSIONS: We proposed three radiomic zones with different standard uptake value characteristics and created four risk groups of prostate cancer patients for testing this idea. We showed that these radiomic zones have different predicting strengths in classifying risk groups and might allow us to identify a radiomic zone with higher accuracy for patient outcome prediction.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study.

BACKGROUND: Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss' kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. RESULTS: Intra-observer agreement was 'good' to 'near perfect' for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were 'high' in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. CONCLUSION: 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

The Heterogeneous Metabolic Patterns of Ganglia in 68Ga-PSMA, 11C-choline, and 18F-FDG PET/CT in Prostate Cancer Patients.

PURPOSE: Studies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM). METHODS: Thirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM. RESULTS: 329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration. CONCLUSION: 68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible.

The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis.

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the "blinded" prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

A retrospective analysis of the diagnostic performance of 11C-choline PET/CT for detection of hyperfunctioning parathyroid glands after prior negative or discordant imaging in primary hyperparathyroidism.

BACKGROUND: Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the diagnostic performance of 11C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging. METHODS: This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing 11C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the 11C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard. RESULTS: In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on 11C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of 11C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions. CONCLUSIONS: In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by 11C-choline PET/CT with high sensitivity and accuracy.

Prognostic Value of Metabolic Imaging Data of 11C-choline PET/CT in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

11C-choline positron emission tomography/computed tomography (PET/CT) has been used for patients with some types of tumors, but few data are available for hepatocellular carcinoma (HCC). We queried our prospective database for patients with HCC staged with 11C-choline PET/CT to assess the clinical impact of this imaging modality. Seven parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), liver standardized uptake value (SUVliver), metabolic tumor volume (MTV), photopenic area, metabolic tumor burden (MTB = MTVxSUVmean), and SUVratio (SUVmax/SUVliver). Analysis was performed to identify parameters that could be predictors of overall survival (OS). Sixty patients were analyzed: fourteen (23%) were in stage 0-A, 37 (62%) in stage B, and 9 (15%) in stage C of the Barcelona classification. The Cox regression for OS showed that Barcelona stages (HR = 2.94; 95%CI = 1.41-4.51; p = 0.003) and MTV (HR = 2.11; 95%CI = 1.51-3.45; p = 0.026) were the only factors independently associated with OS. Receiver operating characteristics curve analysis revealed MTV ability in discriminating survival (area under the curve (AUC) = 0.77; 95%CI = 0.57-097; p < 0.001: patients with MTV ≥ 380 had worse OS (p = 0.015)). The use of 11C-choline PET/CT allows for better prognostic refinement in patients undergoing hepatectomy for HCC. Incorporation of such modality into HCC staging system should be considered.