18F-DOPA PET Research Articles

Short-course hypofractionated proton beam therapy, incorporating 18F-DOPA PET and contrast-enhanced MRI targeting, for patients aged 65 years and older with newly diagnosed glioblastoma: a single-arm phase 2 trial.

Older patients (aged ≥65 years) with glioblastoma have a worse prognosis than younger patients and a median overall survival of 6-9 months. 3,4-Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA) PET sensitively and specifically identifies metabolically active glioblastoma for preferential targeting. Proton beam therapy potentially improves quality of life (QOL) by sparing more healthy brain tissue than photon radiotherapy. With improved targeting and the dosimetric advantages of proton beam therapy, we aimed to test whether hypofractionated proton beam therapy could improve survival and QOL in older patients with glioblastoma. In this single-arm phase 2 trial, we enrolled patients aged 65 years and older with an Eastern Cooperative Oncology Group performance status score of 0-2 and newly diagnosed WHO grade 4, malignant glioblastoma from two Mayo Clinic campuses (Phoenix, AZ, and Rochester, MN, USA). Radiotherapy target volumes were defined by 18F-DOPA PET and MRI regions of contrast enhancement. Patients were given dose-escalated hypofractionated proton beam therapy (35-40 Gy equivalents in five or ten treatments) plus oral concurrent temozolomide (75 mg/m2 daily on days 1-7 for the five-treatment regimen or on days 1-14 for the ten-treatment regimen), and 1 month after completing radiotherapy patients were given adjuvant temozolomide (150-200 mg/m2 on days 1-5 for six 28-day cycles). The primary endpoint was overall survival at 12 months after enrolment. The primary endpoint and safety were assessed in the intention-to-treat population (defined as all eligible patients who started radiotherapy). This study is registered with ClinicalTrials.gov, NCT03778294, and is now complete. Between May 22, 2019, and May 25, 2021, 43 patients were enrolled, of whom four did not receive treatment because of progression (n=2), death (n=1), or insurance denial (n=1), such that 39 patients received treatment (median age 70·2 years [IQR 67·4-74·3]; 11 [28%] of 39 patients were female, 28 [72%] were male, 37 [95%] were White, one [3%] was Black or African American, and one chose not to disclose their race). As of data cutoff (Jan 30, 2024), median follow-up was 25·4 months (IQR 22·1-29·7). 22 (56% [95% CI 39-72]) of 39 patients were alive at 12 months. Median overall survival was 13·1 months (95% CI 11·1-19·1). Grade 3 baseline-adjusted, treatment-associated adverse events were CNS necrosis (four [10%] of 39) and thrombocytopenia (one [3%]). No baseline-adjusted, treatment-associated grade 4 adverse events or deaths occurred. We observed improved overall survival compared with historical controls and a promising adverse event profile by using 18F-DOPA PET-guided, dose-escalated, hypofractionated proton beam therapy. These findings have resulted in the opening of a phase 2 study (NCT05781321) investigating this regimen versus standard-of-care treatment in adults of any age with newly diagnosed glioblastoma. Mayo Clinic Marley Endowment Funds and the Lawrence W and Marilyn W Matteson Fund in Cancer Research.

A New Tool for Extracting Static and Dynamic Parameters from [18F]F-DOPA PET/CT in Pediatric Gliomas

Background/Objectives: PET imaging with [18F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. Methods: In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [18F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [18F]F-DOPA uptake. A total of 73 subjects with treatment-naïve low- and high-grade gliomas, who underwent brain MRI within two weeks of [18F]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. Results: For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357); however, significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Conclusions: Our framework aids in analyzing [18F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

The role of [18F]FDOPA PET as an adjunct to conventional MRI in the diagnosis of aggressive glial lesions.

Amino acid PET is recommended for the initial diagnosis of brain lesions, but its value for identifying aggressive lesions remains to be established. The current study therefore evaluates the added-value of dynamic [18F]FDOPA PET as an adjunct to conventional MRI for determining the aggressiveness of presumed glial lesions at diagnosis. Consecutive patients, with a minimal 1 year-follow-up, underwent contrast-enhanced MRI (CE MRI) and dynamic [18F]FDOPA PET to characterize their suspected glial lesion. Lesions were classified semi-automatically by their CE MRI (MRI-/+), and PET parameters (static tumor-to-background ratio, TBR; dynamic time-to-peak ratio, TTPratio). Diagnostic accuracies of MRI and PET parameters for the differentiation of tumor aggressiveness were evaluated by chi-square test or receiver operating characteristic analyses. Aggressive lesions were either defined as lesions with dismal molecular characteristics based on the WHO 2021 classification of brain tumors or with compatible clinico-radiological profiles. Time-to-treatment failure (TTF) and overall survival (OS) were evaluated. Of the 109 patients included, 46 had aggressive lesions (45 confirmed by histo-molecular analyses). CE MRI identified aggressive lesions with an accuracy of 73%. TBRmax (threshold of 3.2), and TTPratio (threshold of 5.4min) respectively identified aggressive lesions with an accuracy of 83% and 76% and were independent of CE MRI and clinical factors in the multivariate analysis. Among the MRI-lesions, 11/56 (20%) were aggressive and respectively 55% and 50% of these aggressive lesions showed high TBRmax and short TTPratio in PET. High TBRmax and short TTPratio in PET were significantly associated to poorer survivals (p ≤ 0.009). Dynamic [18F]FDOPA PET provides a similar diagnostic accuracy as contrast enhancement in MRI to identify the aggressiveness of suspected glial lesions at diagnosis. Both methods, however, are complementary and [18F]FDOPA PET may be a useful additional tool in equivocal cases.

Amino-acid PET as a prognostic tool after post Stupp protocol temozolomide therapy in high-grade glioma patients

PurposeThis study aimed to evaluate the prognostic performance of amino-acid PET in high-grade gliomas (HGG) patients at the time of temozolomide (TMZ) treatment discontinuation, after the Stupp protocol.MethodsThe analysis included consecutive HGG patients with dynamic [18F]FDOPA PET imaging within 3 months of the end of TMZ therapy, post-Stupp protocol. Static and dynamic PET parameters, responses to RANO criteria for MRI and clinical and histo-molecular factors were correlated to progression-free (PFS).ResultsThirty-two patients (59.4 [54.0;67.6] years old, 13 (41%) women) were included. Static PET parameters peak tumor-to-background ratio and metabolic tumor volume (respective thresholds of 1.9 and 1.5 mL) showed the best 84% accuracies for predicting PFS at 6 months (p = 0.02). These static PET parameters were also independent predictor of PFS in multivariate analysis (p ≤ 0.05).ConclusionIn HGG patients having undergone a Stupp protocol, the absence of significant PET uptake after TMZ constitutes a favorable prognostic factor.

Paragangliomas of the Head and Neck: A Review of the Latest Diagnostic and Treatment Methods.

Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100,000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as 18F-FDA and 18F-FDG PET/CT, 18F-DOPA PET, 123I-MIBG, and 68Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

510 Dopaminergic Neuronal Cell Therapy for Parkinson’s Disease: Results From a Phase 1 Study of Bemdaneprocel

INTRODUCTION: None of the available therapies for PD directly address the loss of dopaminergic neurons. Bemdaneprocel is an investigational cellular therapy composed of midbrain dopaminergic neuronal cells derived from human embryonic stem cells. METHODS: In this open-label study 12 subjects have received 1 of 2 doses of bemdaneprocel to the putamen bilaterally, along with a 1-year immunosuppression regimen. Safety and tolerability have been assessed, along with assessments of engraftment and clinical impact. RESULTS: At screening, the average age was 66.4 yrs and the mean time since diagnosis was 9.1 yrs. All subjects presented at screening with a Hoehn and Yahr stage of 2 in the on-medication state. The mean MDS-UPDRS part III score was 46.6 (15-73) when assessed in the off-medication state, and patients presented with 4.3 (1.4-6.2) average daily hours of OFF time as assessed by PD diaries. In both cohorts, the safety profile is favorable with the vast majority of reported treatment-emergent AEs being mild to moderate. All but one AE deemed potentially related to the intervention were attributed to the immunosuppression regimen. There were no AEs reported as possibly related to the cell therapy. Patients enrolled in both cohorts to date have demonstrated clinical improvement as measured by the MDS-UPDRS, PD diaries, PDQ-39, and others. F-DOPA PET imaging supports evidence of engraftment, survival and functionality of the cells at 1 year. CONCLUSIONS: Results from at least 1 year of follow-up in this phase 1 study will be presented. An acceptable safety profile, evidence of sustained engraftment, and positive exploratory clinical outcomes in this study support further investigation of bemdaneprocel for the treatment of PD. Unpublished data, will be partly shown in a poster at MDS

Mismatch Between Brain MRIs and 18 F-DOPA PET/CT : Impact on the Management of a Long Survivor With EGFR-Mutated Lung Adenocarcinoma.

After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.

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.

Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis.

In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.

Evaluation of Parkinson's disease early diagnosis using single-channel EEG features and auditory cognitive assessment.

Parkinson's disease (PD) often presents with subtle early signs, making diagnosis difficult. F-DOPA PET imaging provides a reliable measure of dopaminergic function and is a primary tool for early PD diagnosis. This study aims to evaluate the ability of machine-learning (ML) extracted EEG features to predict F-DOPA results and distinguish between PD and non-PD patients. These features, extracted using a single-channel EEG during an auditory cognitive assessment, include EEG feature A0 associated with cognitive load in healthy subjects, and EEG feature L1 associated with cognitive task differentiation. Participants in this study are comprised of cognitively healthy patients who had undergone an F-DOPA PET scan as a part of their standard care (n = 32), and cognitively healthy controls (n = 20). EEG data collected using the Neurosteer system during an auditory cognitive task, was decomposed using wavelet-packet analysis and machine learning methods for feature extraction. These features were used in a connectivity analysis that was applied in a similar manner to fMRI connectivity. A preliminary model that relies on the features and their connectivity was used to predict initially unrevealed F-DOPA test results. Then, generalized linear mixed models (LMM) were used to discern between PD and non-PD subjects based on EEG variables. The prediction model correctly classified patients with unrevealed scores as positive F-DOPA. EEG feature A0 and the Delta band revealed distinct activity patterns separating between study groups, with controls displaying higher activity than PD patients. In controls, EEG feature L1 showed variations between resting state and high-cognitive load, an effect lacking in PD patients. Our findings exhibit the potential of single-channel EEG technology in combination with an auditory cognitive assessment to distinguish positive from negative F-DOPA PET scores. This approach shows promise for early PD diagnosis. Additional studies are needed to further verify the utility of this tool as a potential biomarker for PD.

Performance of capsule endoscopy for the detection of small intestinal neuroendocrine tumors in familial carcinoid: a prospective single-site study

Background and AimsSmall bowel neuroendocrine tumors are slow growing, clinically silent tumors whose prognosis depends on disease stage. Members of kindreds with a familial form of small intestine neuroendocrine tumors (SI-NET) represent a high-risk population for whom early detection improves disease outcome. The aim was to determine the utility of small bowel capsule endoscopy (SB-CE) for screening high-risk asymptomatic relatives from kindreds with familial carcinoid. Methods174 asymptomatic subjects with a family history (≥ 2 family members) of SI-NET were screened under Protocol NCT00646022, Natural History of Familial Carcinoid Tumor at the National Institutes of Health. All patients were imaged with SB-CE and 18F-DOPA PET/CT and results were independently analyzed. Patients with a positive imaging study underwent surgical exploration. ResultsThirty-five of 174 asymptomatic subjects screened for SI-NET were positive on either SB-CE or 18F-DOPA PET. Thirty-two of 35 patients with a positive study were confirmed at surgery. SB-CE was positive in 28 of 32 patients with confirmed tumors for a per patient sensitivity of 87.5%. SB-CE had a specificity of 97.3% and a negative predictive value (NPV) of 96.5%. The average tumor number and size was 7.7 and 5.0 mm, respectively, and 81.2% of patients had multiple tumors. 18F-DOPA PET/CT imaging had a similar sensitivity of 84% versus surgery. ConclusionsSB-CE is a sensitive and specific method comparable to 18F-DOPA PET/CT for screening high-risk patients with familial SI-NET.

OR08-04 Paradigm Shift In SDHAF2-Related Familial Paraganglioma Syndrome

Abstract Disclosure: A. Fernandez-Pombo: None. G. Rodriguez-Carnero: None. N. Otero Mato: None. J. Cameselle Teijeiro: None. L. Loidi: None. Z. Nogareda Seoane: None. V. Pubul Nunez: None. M. Martinez Olmos: None. J. Cabezas Agricola: None. Introduction: The recommendations of the clinical practice guidelines regarding the management of SDHAF2-related familial paraganglioma syndrome are based on what is described in the literature in relation to two carrier families of the p.Gly78Arg variant in this gene. To date, among other characteristics, paragangliomas (PGLs) have been thought to occur exclusively in the head and neck, with no metastatic disease observed. Objective: To describe the clinical profile of SDHAF2-related familial paraganglioma syndrome in order to increase knowledge of this disorder. Subjects and Methods: A total of 64 individuals were evaluated after the detection of 7 index cases with the same pathogenic variant (p.Gly78Arg) in the SDHAF2 gene. The clinical data of the 46 patients found to be carrying this variant were collected. In addition to the molecular study, these patients underwent a biochemical evaluation, as well as anatomical imaging. PET with 68Ga-DOTA- TOC and 18F-DOPA were also carried out. The surgical specimens were analyzed. Results: A total of 27 patients developed the disease, with a mean age of 37.0 ± 17.2 years at diagnosis (59.2% women). Inheritance in affected patients was of paternal origin in all known cases. All patients manifested PGLs in the head and neck (96.3% carotid bifurcation, 25.9% jugulotympanic and 14.8% glomus vagale), with a high frequency of multifocality (85.2%). Six patients also manifested mediastinal PGLs (retrocardiac, paraaortic, epicardial, paratracheal, phrenic nerve) and two normetanephrine-secreting pheochromocytomas. All extraadrenal PGLs were non-functioning, with the exception of one case with hypersecretion of 3-methoxytyramine. Throughout the follow-up, three patients manifested distant metastasis (bone and lung metastases). Surgical treatment occurred in 85.1% of cases, radiotherapy in 29.6%, radiosurgery in 14.8% and sunitinib in one case, and 58.3% patients reported some type of complication. 68Ga-DOTA-TOC PET was superior to 18F-DOPA PET in identifying extraadrenal PGLs and metastatic involvement, with an overall detection rate of 100% in the case of 68Ga-DOTA-TOC PET (SUVmax 87.6 ± 60.3 g/ml) and 61.0% in the case of 18F-DOPA PET (SUVmax 19.0 ± 16.2 g/ml), p <0.0001. Regarding the immunohistochemical analysis, no positivity for SDHB was observed and Ki-67 index was <3% in all cases. Conclusions: Certain phenotypic variations have been observed in the current study regarding SDHAF2-related familial paraganglioma syndrome, which have not previously been described and which will contribute to modifying the management of this disease. Presentation: Friday, June 16, 2023

P17.10.B VOLUMETRIC DIFFERENCES IN TARGET DEFINITON OF RECURRENT HIGH-GRADE GLIOMAS USING CONTRAST ENHANCED MRI VS.[18F] FDOPA PET IN RADIOSURGICAL PLANNING

Abstract BACKGROUND Radiosurgical treatment of high-grade gliomas usually bases target definition on contrast-enhanced T1-weighted MRI images. Despite advances in several MRI techniques, a number of limitations exist, primarily due to the disruption of the blood-brain barrier, making the target delineation less accurate, particularly when treating recurrences. Several studies support the use of amino acid PET/MRI in distinguishing progression from post-operative/post-radiation inflammation. However, no established guidelines define the biological target volume when using amino acid PET/MRI in radiosurgical treatment planning. We aimed to explore the volumetric differences in target volumes obtained with standard contrast-enhanced MRI versus [18F]FDOPA PET in patients with recurrent high-grade gliomas (rHGG). MATERIAL AND METHODS Ten patients obtained [18F]FDOPA PET/MRI within 1 week before radiosurgical treatment. We co-registered these images with the 3D MPRAGE-MRI typically used for stereotactic target definition and performed a follow-up PET/MRI scan 4-6 weeks after treatment. We reviewed and compared the method of tumor delineation, target volumes, and stereotactic accuracy in both modalities. RESULTS Radiosurgical treatment delivers high radiation doses to defined targets. The target volume and the proximity to eloquent structures limit the dose, thus depending on high-accuracy imaging. The invasive nature of malignant brain tumors makes anatomical delineation insufficient, particularly when treating recurrences. In such cases, amino acid PET supplies additional information. However, the spatial resolution afforded by [18F]FDOPA uptake alone is insufficient for stereotactic definition, which to a large degree is based on contrast-enhanced T1-weighted MRI images in order to achieve the sub-millimeter resolution needed for radiosurgical planning. Hybrid PET/MRI allows the combination of metabolic information of [18F]FDOPA-PET with the anatomical precision of stereotactic MRI. In the recurrent setting, [18F]FDOPA-PET supplies the necessary information for targeting the biologically active tumour, differentiating it from radiation necrosis, thus limiting the target volumes. This enables us to treat the recurrent tumours more efficiently. CONCLUSION [18F]FDOPA-PET is a useful supplement in radiosurgical planning and treatment of rHGG. It is helpful in the delineation of the biologically active tumor, thus limiting the target volume significantly. This enables higher radiation doses and potentially more efficient treatment. Further results will be presented.

Challenges in the management of hyperinsulinemic hypoglycemia in a preterm neonate - A case report and literature review

Hyperinsulinemic hypoglycemia (HH) includes a diverse group of disorders characterized by dysregulated insulin secretion, exhibiting clinical, genetic, and morphological heterogeneity. It is associated with permanent brain damage. Hence, a timely diagnosis and prompt management are essential to safeguard against complications such as epilepsy, cerebral palsy, and neurodevelopmental deficits. We report the challenges faced in the management of HH in a preterm neonate. A baby girl was born to a G2A1 mother at 31 weeks of gestation due to preterm onset of labor with premature rupture of membranes. The baby had persistent and refractory hypoglycemia requiring oral and parenteral medications such as diazoxide, hydrochlorothiazide, hydrocortisone, nifedipine, glucagon infusion, and subcutaneous octreotide. Genetic testing unveiled a homozygous pathogenic mutation of the ABCC8 gene with autosomal recessive (AR) inheritance. As the AR inheritance always presents with diffuse lesions, a 18F-fluoro-dihydroxyphenylalanine positron emission computed tomography (18F-DOPA PET) scan was not done to differentiate focal and diffuse lesions. The baby underwent laparoscopic near-total pancreatectomy and was discharged on subcutaneous octreotide. Continuous intravenous glucagon infusion may help reduce the infusion rate of glucose needed to maintain normoglycemia. Diazoxide unresponsiveness in a baby with HH needs genetic studies. AR inheritance always presents as diffuse lesions. Hence, an 18F-DOPA PET scan can be deferred to differentiate the diffuse and focal forms.

203 18F-DOPA PET Scan Mapped with Radiotherapy Dosimetry for the Management of Tumour Recurrence Versus Radiation Necrosis in High Grade Gliomas: An Institutional Experience

203 18F-DOPA PET Scan Mapped with Radiotherapy Dosimetry for the Management of Tumour Recurrence Versus Radiation Necrosis in High Grade Gliomas: An Institutional Experience

Head-to-head comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome

Head-to-head comparison of [18F]-FDOPA PET and [123I]-FP-CIT SPECT for assessing nigrostriatal degeneration in patients with a clinically uncertain parkinsonian syndrome

T2-Fluid-attenuated inversion recovery (FLAIR) pseudoprogression in patients with anaplastic oligodendrogliomas treated with procarbazine, lomustine and vincristine (PCV) chemotherapy alone.

Pseudoprogression in gliomas has been extensively described after radiotherapy with or without chemotherapy, but not after chemotherapy alone. Here we describe the occurrence of pseudoprogression in patients with anaplastic oligodendrogliomas treated with postoperative procarbazine, lomustine and vincristine (PCV) chemotherapy alone. We retrospectively reviewed the medical and radiological files of patients with 1p/19q codeleted, IDH-mutant anaplastic oligodendrogliomas treated with PCV chemotherapy alone who presented magnetic resonance imaging (MRI) modifications suggestive of tumour progression and in whom the final diagnosis was a pseudoprogression. We identified six patients. All patients underwent a surgical resection and were treated with PCV chemotherapy without radiotherapy. After a median of 11 months following the initiation of chemotherapy (range: 3-49 months), the patients developed asymptomatic white matter MRI modifications around the surgical cavity leading to the suspicion of a tumour progression. These modifications appeared as hyperintense on T2-fluid-attenuated inversion recovery (FLAIR) sequence, hypointense on T1 sequence, and lacked mass effect (0/6), contrast enhancement (0/6), restriction on diffusion-weighted imaging (0/4), relative cerebral blood volume (rCBV) increase on perfusion MRI (0/4), and hypermetabolism on 18 F-fluoro-L-dopa positron emission tomography (18 F-DOPA PET) scan (0/3). One patient underwent a surgical resection demonstrating no tumour recurrence; the five other patients were considered as having post-therapeutic modifications based on imaging characteristics. After a median follow-up of 4 years all patients were progression-free. Anaplastic oligodendroglioma patients treated with postoperative PCV chemotherapy alone occasionally develop T2/FLAIR hyperintensities around the surgical cavity that can wrongly suggest tumour progression. Multimodal imaging and close follow-up should be considered in this situation.

Therapeutic improvement of Parkinson’s disease transplantation therapy through modulating the immune system.

Abstract We report clinically the implantation of patient-derived midbrain dopaminergic progenitor cells (mDAPs), differentiated in vitrofrom autologous iPSCs, in a patient with idiopathic Parkinson's disease (PD). The patient-specific mDAPs were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with PD, without the need for immunosuppression. Clinical measures of symptoms of PD after surgery stabilized or improved at 18 to 24 months after implantation. Although our previous data (Schweitzer*, Park* et al., NEJM, 382(20) p1926–1932, 2020) showed that using autologous mDAPs can avoid graft rejection, cell survival and functional recovery in the first patient as assessed by 18F-DOPA PET scan analysis and clinical motor assessments was modest, suggesting that survival of mDA neurons may have been suboptimal even in autologous implantation. We have developed a safer and more effective treatment by not only increasing mDA neuron survival by simultaneously controlling the causative immune response, but also by modulating the problematic proliferative property, which is a characteristic of progenitor cells after implantation. In conclusion, our new study suggests that initial, specific mDA neuron survival in these grafts is strongly affected by the host innate immune response, while long-term graft survival is subject to the adaptive immune response, elucidating a two-phase involvement of the immune system for graft survival. This work was supported by NIH grants (NS070577 and OD024622), the Parkinson’s Cell Therapy Research Fund at McLean Hospital and Massachusetts General Hospital, and the Masson Family Endowed Scholar in Neurosurgery, and the George A. Lopez, MD Endowed Chair in Neurosurgery.