Diagnostic performance of [18 F]FDOPA PET/CT and other tracers in pheochromocytoma: A meta-analysis.

RATIONALE AND OBJECTIVES: PET-CT is extensively used in the diagnosis of pheochromocytoma (PHEO). However, various PET-CT tracers are recommended for the diagnosis of PHEO. Therefore, this study evaluated the diagnostic performance of all tracers currently used in the PET-CT detection of PHEO. METHODS: Studies were retrieved from PubMed, Web of Science, Embase, and Cochrane Library from inception to Feb. 7, 2024. The studies were screened according to the eligibility criteria and the data were extracted. Quality of the included studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (sROC) curve (AUC) were pooled in Stata 15, and diagnostic accuracy was pooled in R 4.3.3. RESULTS: Sixteen studies were included in the meta-analysis. The sensitivity and specificity of [18 F]FDOPA PET/CT for initial PHEO diagnosis were 97% (95% CI: 91%-99%, I2 = 46.14%, p > 0.01) and 94% (95% CI: 86%-98%, I2 = 87.90%, p < 0.01), respectively. The AUC was 0.99 (95% CI: 0.98-1.00). The diagnostic accuracy of [18 F]FDOPA PET/CT was 98.9% (95% CI: 95%-100%) for PHEO patients and 89.7% (95% CI: 85.4%-92.8%) for PHEO lesions. [68Ga]DOTATATE PET/CT had a diagnostic accuracy of 86.9% (95% CI: 78.2%-93.9%) for PHEO and 87.5% (95% CI: 70.3%-95.4%) for PHEO lesions. FDG PET/CT had a diagnostic accuracy of 85.2% (95% CI: 73.6%-94.1%) for PHEO and 86.8% (95% CI: 73%-94.2%) for PHEO lesions. [68Ga]DOTANOC PET/CT had a diagnostic accuracy of 79.3% (95% CI: 49.2%-98.3%) for PHEO. CONCLUSIONS: In general, PET/CT demonstrates superior performance in the diagnosis of PHEO. In addition, [18 F]FDOPA PET/CT has the best diagnostic performance in PHEO compared with other tracers. Given the limited research on other PET/CT tracers and the potential constraints on their widespread use, additional multicenter and multiregional studies are warranted to further evaluate their diagnostic performance and provide recommendations for clinical use.

Complex Diagnostic Challenges in Glioblastoma: The Role of 18F-FDOPA PET Imaging.

Glioblastoma multiforme (GBM) remains one of the most aggressive and lethal forms of brain cancer, characterized by rapid proliferation and diffuse infiltration into the surrounding brain tissues. Despite advancements in therapeutic approaches, the prognosis for GBM patients is poor, with median survival times rarely exceeding 15 months post-diagnosis. An accurate diagnosis, treatment planning, and monitoring are crucial for improving patient outcomes. Core imaging modalities such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are indispensable in the initial diagnosis and ongoing management of GBM. Histopathology remains the gold standard for definitive diagnoses, guiding treatment by providing molecular and genetic insights into the tumor. Advanced imaging modalities, particularly positron emission tomography (PET), play a pivotal role in the management of GBM. Among these, 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-FDOPA) PET has emerged as a powerful tool due to its superior specificity and sensitivity in detecting GBM and monitoring treatment responses. This introduction provides a comprehensive overview of the multifaceted role of 18F-FDOPA PET in GBM, covering its diagnostic accuracy, potential as a biomarker, integration into clinical workflows, impact on patient outcomes, technological and methodological advancements, comparative effectiveness with other PET tracers, and its cost-effectiveness in clinical practice. Through these perspectives, we aim to underscore the significant contributions of 18F-FDOPA PET to the evolving landscape of GBM management and its potential to enhance both clinical and economic outcomes for patients afflicted with this formidable disease.

Automation of Copper-Mediated 18F-Fluorination of Aryl Pinacol Boronates Using 4-Dimethylaminopyridinium Triflate.

Currently, the copper-mediated radiofluorination of aryl pinacol boronates (arylBPin) using the commercially available, air-stable Cu(OTf)2Py4 catalyst is one of the most efficient synthesis approaches, greatly facilitating access to a range of radiotracers, including drug-like molecules with nonactivated aryl scaffolds. Further adjustment of this methodology, in particular, the [18F]fluoride recovery step for the routine preparation of radiotracers, has been the focus of recent research. In our recent study, an organic solution of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAPOTf) was found to be an efficient PTC for eluting radionuclides retained on the weak anion exchange cartridge, Oasis WAX 1cc, employing the inverse sorption-elution protocol. Notably, the following Cu-mediated radiofluorination of arylBPin precursors in the presence of the Cu(OTf)2(Py)4 catalyst can be performed with high efficiency in the same solvent, bypassing not only the conventional azeotropic drying procedure but any solvent replacement. In the current study, we aimed to translate this methodology, originally developed for remote-controlled operation with manual interventions, into the automated synthesis module on the TRACERlab automation platform. The adjustment of the reagent amounts and solvents allowed for high efficiency in the radiofluorination of a series of model arylBPin substrates on the TRACERlab FXFE Pro synthesis module, which was adapted for nucleophilic radiofluorinations. The practical applicability of the developed radiofluorination approach with DMAPOTf elution was demonstrated in the automated synthesis of 6-L-[18F]FDOPA. The radiotracer was obtained with an activity yield (AY; isolated, not decay-corrected) of 5.2 ± 0.5% (n = 3), with a synthesis time of ca. 70 min on the TRACERlab FX N Pro automation platform. The obtained AY was comparable with one reported by others (6 ± 1%) using the same boronate precursor, while a slightly higher AY of 6-L-[18F]FDOPA (14.5 ± 0.5%) was achieved in our previous work using commercially available Bu4NOTf as the PTC.

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.

Validation of cardiac image-derived input functions for functional PET quantification.

PURPOSE: Functional PET (fPET) is a novel technique for studying dynamic changes in brain metabolism and neurotransmitter signaling. Accurate quantification of fPET relies on measuring the arterial input function (AIF), traditionally achieved through invasive arterial blood sampling. While non-invasive image-derived input functions (IDIF) offer an alternative, they suffer from limited spatial resolution and field of view. To overcome these issues, we developed and validated a scan protocol for brain fPET utilizing cardiac IDIF, aiming to mitigate known IDIF limitations. METHODS: Twenty healthy individuals underwent fPET/MR scans using [18F]FDG or 6-[18F]FDOPA, utilizing bed motion shuttling to capture cardiac IDIF and brain task-induced changes. Arterial and venous blood sampling was used to validate IDIFs. Participants performed a monetary incentive delay task. IDIFs from various blood pools and composites estimated from a linear fit over all IDIF blood pools (3VOI) and further supplemented with venous blood samples (3VOIVB) were compared to the AIF. Quantitative task-specific images from both tracers were compared to assess the performance of each input function to the gold standard. RESULTS: For both radiotracer cohorts, moderate to high agreement (r: 0.60-0.89) between IDIFs and AIF for both radiotracer cohorts was observed, with further improvement (r: 0.87-0.93) for composite IDIFs (3VOI and 3VOIVB). Both methods showed equivalent quantitative values and high agreement (r: 0.975-0.998) with AIF-derived measurements. CONCLUSION: Our proposed protocol enables accurate non-invasive estimation of the input function with full quantification of task-specific changes, addressing the limitations of IDIF for brain imaging by sampling larger blood pools over the thorax. These advancements increase applicability to any PET scanner and clinical research setting by reducing experimental complexity and increasing patient comfort.

Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient.

Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.

[18F]FDOPA PET/CT in Solid Pseudopapillary Tumor of the Pancreas: a Recurred Tumor Mimicking Splenosis.

Solid pseudopapillary tumor (SPT) of the pancreas is a neoplasm with low malignant potential. It is often challenging to diagnose SPT due to its nonspecific clinical and radiological features, and [18F]FDOPA is effective in diagnosing SPT, particularly in differentiating SPT from benign conditions such as splenosis. A 55-year-old woman underwent distal pancreatectomy and splenectomy for histologically confirmed SPT. She was also initially diagnosed with splenosis. During follow-up, sizes of multiple nodular lesions were increased, raising the possibility of peritoneal seeding of SPT. For diagnosis, a spleen scan and SPECT/CT were performed using 99mTc-labeled damaged red blood cells, which showed no uptake in the peritoneal nodules. Subsequent [18F]FDOPA PET/CT revealed [18F]FDOPA-avidity of the nodules. The patient underwent tumor resection surgery, and the nodules were pathologically confirmed as SPT.

Decoupling Dopamine Synthesis from Impulsive Action, Risk-Related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [18F]-FDOPA PET Study in Roman High- and Low-Avoidance Rats.

Impulsive action and risk-related decision-making (RDM) are two facets of impulsivity linked to a hyperdopaminergic release in the striatum and an increased propensity to cocaine intake. We previously showed that with repeated cocaine exposure, this initial hyperdopaminergic release is blunted in impulsive animals, potentially signaling drug-induced tolerance. Whether such dopaminergic dynamics involve changes in dopamine (DA) synthesis as a function of impulsivity is currently unknown. Here, we investigated the predictive value of DA synthesis for impulsive action, RDM, and the propensity to take cocaine in a rat model of vulnerability to cocaine abuse. Additionally, we assessed the effects of cocaine intake on these variables. Rats were tested sequentially in the rat Gambling Task (rGT) and were scanned with positron emission tomography and [18F]-FDOPA to respectively assess both impulsivity facets and striatal DA synthesis before and after cocaine self-administration (SA). Our results revealed that baseline striatal levels of DA synthesis did not significantly predict impulsive action, RDM, or a greater propensity to cocaine SA in impulsive animals. Besides, we showed that impulsive action, but not RDM, predicted higher rates of cocaine taking. However, chronic cocaine exposure had no impact on DA synthesis, nor affected impulsive action and RDM. These findings indicate that the hyper-responsive DA system associated with impulsivity and a propensity for cocaine consumption, along with the reduction in this hyper-responsive DA state in impulsive animals with a history of cocaine use, might not be mediated by dynamic changes in DA synthesis.

18F-FDOPA PET/CT Semi-Quantitative Analysis in Improving the Diagnostic Efficacy of Parkinson's Disease / 中国医学影像学杂志

Purpose To investigate the diagnostic value of 18F-FDOPA PET/CT imaging and semi-quantitative analysis platform for the diagnosis of Parkinson's disease(PD).Materials and Methods There were 27 healthy controls and 56 clinically diagnosed PD patients,including 33 early PD(Hoehn-Yahr class Ⅰ-Ⅱ)and 23 advanced PD(Hoehn-Yahr class Ⅲ-Ⅳ),underwent 18F-FDOPA PET imaging in Nanjing First Hospital,Nanjing Medical University were consecutively enrolled from January 2018 to December 2019.The striatal to occipital ratio(SORs)in radioactivity was calculated by HERMES BRASS platform,thereby completing the semi-quantitative analysis of the brain based on regions of interest and observing the asymmetry of the striatal subregions in early-stage PD and late-stage PD patients.Using artificial intelligence techniques to perform principal component analysis on the SORs of the striatal subregions in PD group and healthy control group,the degree of data aggregation and the distinguishability between groups were observed.Results The SORs was significantly reduced in the whole caudate,anterior,posterior putamen and striatum of advanced PD patients(t=9.02-11.72,P<0.000 1).The area under the curve was 0.952,0.973,0.995 and 0.982,respectively.Compared with the healthy control group,the loss of striatal asymmetry index(mean)in each subregion of the striatum in early PD group was caudate(7.61±5.50)%,anterior putamen(11.43±8.97)%,posterior putamen(17.17±11.63)%,and whole striatum(10.65±7.46)%,respectively.The uptake of 18F-FDOPA in the striatum of PD patients was significantly reduced,and the most obvious loss of early PD patients was contralateral posterior putamen,with a decrease of 34%.Conclusion The platform semi-quantitative analysis of 18F-FDOPA PET/CT images provides objective semi-quantitative values for early diagnosis and differential diagnosis of PD.Asymmetry in the striatum,especially in the putamen,may be an important parameter for early diagnosis of PD..

Slowing of EEG waves correlates with striatal [18 F]fluorodopa PET/CT uptake and executive dysfunction in Parkinson's disease.

Parkinson's disease (PD) research on specific neuroimaging and neurophysiological biomarkers revealing executive dysfunction mechanisms is limited, necessitating validation. Thus, our study aimed to assess associations between electroencephalographic power spectral density (PSD-EEG), striatal [18 F]Fluorodopa uptake and neuropsychological executive function (EF) testing parameters in PD, while also estimating their diagnostic accuracy. We compared resting PSD-EEG, striatal [18 F]Fluorodopa uptake ratios based on positron emission computed tomography ([18 F]FDOPA PET/CT) and neuropsychological EF tests outcomes [Trail Making Test (TMT) and Stroop Test (ST)] between PD patients and healthy controls (HCO) and then calculated correlations among these measures separately for each group. Additionally, we estimated PD diagnostic accuracy of the PSD-EEG and [18 F]FDOPA PET/CT parameters. In PD patients, we observed the following: (i) slower EEG waves, reflected in increased power of the EEG theta and lower-alpha bands in frontal lobe areas; (ii) reduced [18 F]FDOPA PET/CT uptake in the putaminal and caudate nuclei, along with a decreased putamen-to-caudate ratio ([18 F]FDOPA PET/CT PCR); and (iii) longer performance times evident in nearly all EF tests' parameters. Slower EEG waves correlated negatively with [18 F]FDOPA PET/CT PCR and positively with most of the EF test parameters. Furthermore, we found negative correlations between [18 F]FDOPA PET/CT PCR and certain EF measures related to ST. [18 F]FDOPA PET/CT ratios and several PSD-EEG parameters, particularly those from the prefrontal cortex, demonstrated clinically reasonable diagnostic accuracy for PD. In conclusion, EEG waves slowing in the frontal lobe were correlated with striatal dopaminergic deficiency and impaired executive function in mild PD patients and showed promise as a biomarker of PD-related executive dysfunction.

High Tumor Uptake on 18F-FDOPA PET/CT Indicates Poor Prognosis in Patients with Metastatic Midgut Neuroendocrine Tumors: A Study from the Groupe d'étude des Tumeurs Endocrines and ENDOCAN-RENATEN Network.

PET/CT with 6-18F-fluoro-l-dopa (18F-FDOPA) has high diagnostic performance for midgut neuroendocrine tumors (NETs). We explored the prognostic role of 18F-FDOPA PET/CT uptake in metastatic midgut NETs. Methods: We included, in a test cohort (n = 166) and a full external validation cohort (n = 86), all consecutive patients with metastatic midgut NETs who underwent 18F-FDOPA PET/CT in 5 expert centers from 2010 to 2021. We measured the maximal uptake (SUVmax and SUVpeak) of the tumor and nontumor liver on each 18F-FDOPA PET/CT scan. We measured overall survival (OS) from the time of PET/CT and assessed prognostic factors using Kaplan-Meier and multivariable Cox proportional-hazards analyses in the test cohort, with replication in the validation cohort. Results: Patients had similar characteristics in both cohorts. In the test cohort, median follow-up was 60.3 mo. Patients with an SUVpeak tumor-to-liver (T/L) ratio of more than 4.2 had significantly shorter survival than those with a ratio of 4.2 or less (P = 0.01), with a 5-y OS rate of 74.1% ± 4.5% versus 95% ± 3.4%, respectively. On multivariable analysis, an SUVpeak T/L ratio of more than 4.2 remained associated with shorter OS (hazard ratio, 2.30; 95% CI, 1.02-5.22; P = 0.046) after adjustment for age, grade, number of previous lines, number of metastatic sites, and presence of carcinoid syndrome. In the validation cohort, the 5-y OS rate was 100% versus 57.8% ± 12.5% in patients with an SUVpeak T/L ratio ≤ 4.2 or > 4.2, respectively (P = 0.075). An increasing SUVpeak T/L ratio over time tended to have a pejorative prognostic impact. Conclusion: Tumor uptake on 18F-FDOPA PET/CT is an independent prognostic factor in patients with metastatic midgut NETs.

Dopamine Synthesis Capacity and GABA and Glutamate Levels Separate Antipsychotic-Naïve Patients With First-Episode Psychosis From Healthy Control Subjects in a Multimodal Prediction Model.

Background: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects. Methods: We included 23 patients (mean age 22.3 years, 9 male) and 20 control subjects (mean age 22.4 years, 8 male). We determined dopamine metabolism in the nucleus accumbens and striatum from 18F-fluorodopa (18F-FDOPA) positron emission tomography. We measured GABA levels in the anterior cingulate cortex (ACC) and glutamate plus glutamine levels in the ACC and left thalamus with 3T proton magnetic resonance spectroscopy. We used binominal logistic regression for unimodal prediction when we modeled neurotransmitters individually and for multimodal prediction when we combined the 3 neurotransmitters. We selected the best combination based on Akaike information criterion. Results: Individual neurotransmitters failed to predict group. Three triple neurotransmitter combinations significantly predicted group after Benjamini-Hochberg correction. The best model (Akaike information criterion 48.5) carried 93.5% of the cumulative model weight. It reached a classification accuracy of 83.7% (p = .003) and included dopamine synthesis capacity (Ki4p) in the nucleus accumbens (p = .664), GABA levels in the ACC (p = .019), glutamate plus glutamine levels in the thalamus (p = .678), and the interaction term Ki4p × GABA (p = .016). Conclusions: Our multimodal approach proved superior classification accuracy, implying that the pathophysiology of patients represents a combination of neurotransmitter disturbances rather than aberrations in a single neurotransmitter. Particularly aberrant interrelations between Ki4p in the nucleus accumbens and GABA values in the ACC appeared to contribute diagnostic information.

Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study.

BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.

The Role of 18F-FDOPA PET/CT in Recurrent Medullary Thyroid Cancer Patients with Elevated Serum Calcitonin Levels.

Objectives: To evaluate the diagnostic performance of 18F-dihydroxyphenylalanine (FDOPA) positron emission tomography/computed tomography (PET/CT) in the detection of medullary thyroid carcinoma (MTC) recurrence in patients with elevated calcitonin levels. Methods: The patients who had undergone 18F-FDOPA PET/CT imaging for elevated calcitonin levels after primary surgery of MTC were included in the study. addition, if available 18F-fluorodeoxyglucose (FDG) PET/CT and Gallium-68 (68Ga)- DOTATATE PET/CT images of the patients were evaluated retrospectively. The sensitivity and diagnostic performance of 18F-DOPA PET/CT were investigated. Results: A total of 14 patients (9 F and 5 M; median age: 45) were included in the analysis. Three patients had MEN IIA syndrome and 1 patient had MEN IIB syndrome, 10 patients had a diagnosis of sporadic MTC. Median calcitonin levels of the patients were calculated as 757.5 (min-max: 28.5-7911) pg/mL. Nine patients and 5 patients had undergone ultrasound and contrast-enhanced computed tomography (ceCT) of the neck, respectively, before 18F-FDOPA PET/CT imaging. 18F-FDOPA PET/CT revealed pathological uptake in the thyroid bed, lymph nodes, and distant organs in three, five and two patients, respectively. Median maximum standardized uptake value for the recurrent or metastatic lesions were calculated as 6.4 (min-max: 1.9-18.4). The sensitivity of 18F-FDOPA PET/CT in the detection of recurrent disease was calculated as 64%. Eight patients had 68Ga-DOTATATE PET/CT and 7 of them had 18F-FDG PET/CT within 3 months period before 18F-FDOPA PET/CT. 18F-FDOPA PET/CT revealed recurrent disease in 4 of 5 and 2 of the 5 patients who had negative 18F-FDG PET/CT and negative 68Ga- DOTATATE PET/CT, respectively. Conclusion: 18F-FDOPA PET/CT can detect recurrence in about two- thirds of patients with elevated calcitonin levels after primary surgery for MTC. Due to variable differentiation degree, different receptor status, and clinical behavior of MTC, all three radiopharmaceuticals can be beneficial and are complementary to each other in patient management.

Differentiating high-grade glioma progression from treatment-related changes with dynamic [18F]FDOPA PET: a multicentric study.

OBJECTIVES: Diagnostic accuracy of amino-acid PET for distinguishing progression from treatment-related changes (TRC) is currently based on single-center non-homogeneous glioma populations. Our study assesses the diagnostic value of static and dynamic [18F]FDOPA PET acquisitions to differentiate between high-grade glioma (HGG) recurrence and TRC in a large cohort sourced from two independent nuclear medicine centers. METHODS: We retrospectively identified 106 patients with suspected glioma recurrences (WHO GIII, n = 38; GIV, n = 68; IDH-mutant, n = 35, IDH-wildtype, n = 71). Patients underwent dynamic [18F]FDOPA PET/CT (n = 83) or PET/MRI (n = 23), and static tumor-to-background ratios (TBRs), metabolic tumor volumes and dynamic parameters (time to peak and slope) were determined. The final diagnosis was either defined by histopathology or a clinical-radiological follow-up at 6 months. Optimal [18F]FDOPA PET parameter cut-offs were obtained by receiver operating characteristic analysis. Predictive factors and clinical parameters were assessed using univariate and multivariate Cox regression survival analyses. RESULTS: Surgery or the clinical-radiological 6-month follow-up identified 71 progressions and 35 treatment-related changes. TBRmean, with a threshold of 1.8, best-differentiated glioma recurrence/progression from post-treatment changes in the whole population (sensitivity 82%, specificity 71%, p < 0.0001) whereas curve slope was only significantly different in IDH-mutant HGGs (n = 25). In survival analyses, MTV was a clinical independent predictor of progression-free and overall survival on the multivariate analysis (p ≤ 0.01). A curve slope > -0.12/h was an independent predictor for longer PFS in IDH-mutant HGGs CONCLUSION: Our multicentric study confirms the high accuracy of [18F]FDOPA PET to differentiate recurrent malignant gliomas from TRC and emphasizes the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant HGGs. KEY POINTS: • The diagnostic accuracy of dynamic amino-acid PET, for distinguishing progression from treatment-related changes, is currently based on single-center non-homogeneous glioma populations. • This multicentric study confirms the high accuracy of static [18F]FDOPA PET images for differentiating progression from treatment-related changes in a homogeneous population of high-grade gliomas and highlights the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant high-grade gliomas. • Dynamic acquisitions should be performed in IDH-mutant glioma patients to provide valuable information for the differential diagnosis of recurrence and treatment-related changes.

Paragangliomas and Pheochromocytomas: Positron Emission Tomography/Computed Tomography Diagnosis and Therapy.

Molecular imaging evaluation of pheochromocytomas and paragangliomas depends on multiple factors, such as localized versus metastatic disease, the genetic, and biochemical profile of tumors. Positron emission tomography/computed tomography (PET/CT) imaging of these tumors outperforms Meta-Iodo-Benzyl-Guanidine (MIBG) scintigraphy in most cases. A few PET radiotracers have been studied in evaluating these patients with somatostatin receptor PET imaging and have shown superior performance compared with other agents in most of these patients. 18F-fluorodeoxyglucose PET/CT imaging is useful in select patients, such as those with succinate dehydrogenase complex subunit B-associated disease. Treatment strategy depends on multiple factors and necessitates a multidisciplinary approach.

Comparing [18F]FET PET and [18F]FDOPA PET for glioma recurrence diagnosis: a systematic review and meta-analysis.

Purpose: The purpose of our meta-analysis and systematic review was to evaluate and compare the diagnostic effectiveness of [18F]FET PET and [18F]FDOPA PET in detecting glioma recurrence. Methods: Sensitivities and specificities were assessed using the DerSimonian and Laird methodology, and subsequently transformed using the Freeman-Tukey double inverse sine transformation. Confidence intervals were computed employing the Jackson method, while heterogeneity within and between groups was evaluated through the Cochrane Q and I² statistics. If substantial heterogeneity among the studies was observed (P < 0.10 or I² > 50%), we conducted meta-regression and sensitivity analyses. Publication bias was assessed through the test of a funnel plot and the application of Egger's test. For all statistical tests, except for assessing heterogeneity (P < 0.10), statistical significance was determined when the two-tailed P value fell below 0.05. Results: Initially, 579 publications were identified, and ultimately, 22 studies, involving 1514 patients(1226 patients for [18F]FET PET and 288 patients for [18F]FDOPA PET), were included in the analysis. The sensitivity and specificity of [18F]FET PET were 0.84 (95% CI, 0.75-0.90) and 0.86 (95% CI, 0.80-0.91), respectively, while for [18F]FDOPA PET, the values were 0.95 (95% CI, 0.86-1.00) for sensitivity and 0.90 (95% CI, 0.77-0.98) for specificity. A statistically significant difference in sensitivity existed between these two radiotracers (P=0.04), while no significant difference was observed in specificity (P=0.58). Conclusion: It seems that [18F]FDOPA PET demonstrates superior sensitivity and similar specificity to [18F] FET PET. Nevertheless, it's crucial to emphasize that [18F]FDOPA PET results were obtained from studies with limited sample sizes. Further larger prospective studies, especially head-to-head comparisons, are needed in this issue. Systematic Review Registration: identifier CRD42023463476.

Comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT acquired in clinical practice for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome.

PURPOSE: Two commonly used imaging techniques to aid in the diagnosis of neurodegenerative parkinsonian syndromes are dopamine transporter (DAT) imaging with [123I]-FP-CIT single-photon emission computed tomography (DAT-SPECT) and positron emission tomography with [18F]-FDOPA (FDOPA-PET). This paper provides a unique series of parkinsonian patients who received both FDOPA-PET and DAT-SPECT in routine clinical practice and compares the reported results to assess potential differences between these two imaging techniques. METHODS: We present 11 patients with a clinically uncertain parkinsonian syndrome (CUPS), who received both FDOPA-PET and DAT-SPECT. All patients received an FDOPA-PET scan and DAT-SPECT as part of routine clinical care. RESULTS: The median time between the F-DOPA-PET scan and DAT-SPECT scan was 6 months (range 0-15 months). There was a discrepancy in the reported results of the FDOPA-PET and DAT-SPECT scans in nine patients, including 7 patients whose FDOPA-PET scan was reportedly normal, whereas their DAT-SPECT scan was abnormal. CONCLUSIONS: In this case series of CUPS patients, DAT-SPECT was more often rated as abnormal than FDOPA-PET. The striatal loss of FDOPA uptake can be less pronounced than that of DAT binding in CUPS patients in early disease stages. Consequently, the interpretation of FDOPA-PET scans in CUPS can sometimes be challenging in routine practice.

Case Report: 18F-Fluoro-L-Phenylalanine Positron Emission Tomography Findings and Immunoreactivity for L-Type Amino Acid Transporter 1 in a Dog With Meningioma.

A 12-year-old intact female Miniature Pinscher dog weighing 5.4 kg presented with a history of seizures. On neurological examination, postural reactions were decreased in the left-sided limbs, and menace responses were bilaterally absent. Magnetic resonance imaging (MRI) of the brain was performed, and a solitary amorphous mass (2.7 × 1.9 × 2.2 cm) was observed on the right side of the frontal lobe. Based on the signalment, clinical signs, and MRI findings, a brain tumor was tentatively diagnosed, and meningioma was suspected. The dog was treated with hydroxyurea, prednisolone, and other antiepileptic drugs. One week after the treatment began, postural reactions returned to normal, and the menace response improved. At 119 days after treatment, 18F-fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) was performed. Marked 18F-FDOPA uptake was observed in the lesion. The mean and maximal standardized uptake values of the lesion were 2.61 and 3.72, respectively, and the tumor-to-normal tissue ratio was 1.95. At 355 days after the initial treatment, a second MRI scan was performed and the tumor size had increased to 3.5 × 2.8 × 2.9 cm. The dog died 443 days after the initial treatment and was definitively diagnosed with grade 1 meningioma by histopathological examination. Immunohistochemical staining for Ki67 and L-type amino acid transporter 1 was positive and negative for p53, respectively. The labeling index of Ki67 was 2.4%. This is the first case to demonstrate 18F-FDOPA PET findings in a clinical case of a dog histologically diagnosed with a meningioma.