PET Imaging Research Articles

OGC SO21 - Role of Staging Laparoscopy on oesophageal and junctional cancer management

Abstract Background Staging laparoscopy and peritoneal cytology is currently recommended as a staging tool required for oesophageal and gastro-oesophageal junction (OGJ) adenocarcinomas. However, evidence is variable regarding the utility of this investigation, leading to heterogenous practice in the UK. With improved staging sensitivity of CT and PET imaging and inclusion of routine MDT discussion for upper GI cancer patients, staging laparoscopy may not be necessary for all patients with oesophago-gastric cancer, and in fact may delay their treatment. We thus aimed to assess the impact of staging laparoscopy on the treatment algorithm of patients with oesophago-gastric cancer. Method All staging laparoscopies undertaken between January 2022 and March 2024 were identified from our surgical database. Patients were included if they had oesophago-gastric adenocarcinoma, with a plan for curative treatment. Data collected included age, gender, location of primary tumour, CT/PET staging, laparoscopy findings, impact on treatment intention, neoadjuvant treatment, and final histology. Primary outcome was incidence of positive microscopic or macroscopic peritoneal disease for oesophageal and OGJ malignancy. Results 127 patients were identified - 69 (55%) oesophageal, 25 (20%) GOJ, and 32 (24.4%) gastric cancer. 1/70 (1.4%) patient diagnosed endoscopically with oesophageal cancer had positive peritoneal disease, which was suspected due to pre-operative imaging findings of ascites and suspicions of linitis plastica. Of patients diagnosed with GOJ cancer, 4/25 patients (16%) had peritoneal disease present. None of the 39 patients with oesophageal/junctional tumours with clinical T1-2 disease were found to have peritoneal disease on staging laparoscopy. 6/32 (19%) patients with gastric cancer were found to have unexpected peritoneal disease present. Conclusion This study found minimal impact staging laparoscopy has on the management of primary oesophageal cancers. Consideration can be made of limiting staging in oesophageal cancer to patients with suspicious findings on CT/PET imaging. For GOJ tumours, there may be a role for limiting staging laparoscopy for Siewert 1 tumours to T3/4 tumours based on CT/PET findings. Importantly, accurate identification on primary endoscopy of the location of the tumour in relation to the gastro-oesophageal junction is necessary to help guide ongoing management.

OGC SO22 - Accuracy of CT and FDG/PET clinical staging within a dedicated multidisciplinary service for patients with oesophago-gastric cancer

Abstract Background Accurate staging for oesophago-gastric cancer is important in ensuring correct treatment pathways, avoiding unnecessary surgery and providing prognostication for patients. Previously, cross sectional imaging in accurately providing tumour (T) and nodal (N) staging has been variable for upper GI malignancies, with usage of invasive investigations such as EUS to provide more specific local staging. With the increased utilisation of specialist multidisciplinary involvement and improved technology, we aimed to assess whether CT and PET imaging may be able to provide sufficiently accurate staging required for treatment decision making. Method All patients who underwent oesoophagogastric resections between January 2022 and March 2024 were identified from our surgical database. Patients were included if they had oesophago-gastric cancer, and underwent curative resection without neo-adjuvant treatment. Data collected included age, gender, location of primary tumour, CT/PET staging, and final histology. Outcomes assessed included rate of understaging in clinical and pathological T and N staging, and sensitivity and specificity of imaging in identifying presence of nodal disease. Results 38 patients were included in this analysis. For oesophageal and GOJ cancers, T stage under-reporting occurred in 6/27 (22%) patients, and N under-reporting in 7/27 (27%) patients. Radiological staging correlated with final pathological staging in 55% of T staging and 59% of N staging. Sensitivity (55.56%, 95% CI 21-86%) and specificity (72.2%, 95% CI 46.5-90.3%) for nodal disease on CT/PET was low, however no tumour or nodal under-staging would have impacted management. Gastric cancer staging accuracy assessment was limited by small numbers (n=12), however T under-staging occurred in 5/12 (42%) patients and N under-staging occurred in 5/11 patients (45%). Conclusion Involvement of dedicated radiology services in multidisciplinary care for oesophago-gastric cancer provides adequate radiological staging to guide treatment. Gastric cancer clinical staging requires laparoscopic and endoscopic assessment for accurate tumour assessment and management guidance. Radiological under-staging is less common in oesophageal and GOJ tumours than gastric cancer and has minimal impact on patient management.

Intrahepatic Cholangiocarcinoma Presenting as an Incidentaloma on F-18 PYL PSMA PET/CT

AbstractCholangiocarcinoma is an aggressive malignancy arising from the biliary tract epithelium with rising incidence and mortality. Imaging commonly used for diagnostic workup includes computed tomography (CT) scan and magnetic resonance imaging (MRI). Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) scans can be used for investigating equivocal findings on radiographic imaging. Prostate-specific membrane antigen (PSMA) is known to be highly expressed in prostate adenocarcinoma, allowing it to be leveraged as a target for both imaging and radioligand therapy in prostate cancer. However, PSMA is also commonly expressed in other malignancies such as breast cancer, thyroid carcinomas, and head and neck malignancies, which increase the chances of their incidental diagnosis on PSMA PET scans. Biliary tract cancers, including cholangiocarcinoma, are not commonly expected to be incidentally diagnosed on PSMA PET imaging. Here, we describe the case of a patient with known prostate adenocarcinoma who was later incidentally diagnosed with advanced intrahepatic cholangiocarcinoma on PSMA PET/computed tomography (CT). This case highlights the unexpected finding of cholangiocarcinoma on PSMA PET/CT and suggests further investigation into the role of PSMA PET in diagnosing ambiguous cases of cholangiocarcinoma and its potential theranostic applications.

Longitudinal FDG-PET Radiomics for Early Prediction of Treatment Response to Chemoradiation in Locally Advanced Cervical Cancer: A Pilot Study

Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC.

Two-Year Experience of a Center of Excellence for the Comprehensive Management of Non-Small Cell Lung Cancer at a Fourth-Level Hospital in Bogota, Colombia: Observational Case Series Study and Retrospective Analysis

Background: This study aimed to provide a comprehensive analysis of 56 patients admitted to the Lung Cancer Clinical Care Center (C3) at Fundación Santa Fe de Bogotá (FSFB) between 2 May 2022 and 22 April 2024. The focus was on demographic characteristics, smoking history, comorbidities, lung cancer types, TNM classification, treatment modalities, and outcomes. Methods: This observational case series study reviewed medical records and included patients over 18 years with a confirmed diagnosis of non-small cell lung cancer (NSCLC). Data were collected and analyzed for demographics, comorbidities, treatment types, biomolecular profiling, and survival rates. Ethical approval was obtained, and data were anonymized. Results: The mean age was 71.8 years with a female predominance (53.6%). A history of smoking was present in 71.4% of patients. Adenocarcinoma was the most common type (75.0%), followed by squamous cell carcinoma (19.6%). At admission, the most frequent TNM stages were IA2 (17.9%) and IVA (16.1%). One-year survival was 68.8%, and 94.3% of stage I–IIIA patients underwent PET scans. Biomolecular profiling revealed 69.2% non-mutated EGFR, 90.4% ALK-negative, and various PDL-1 expression levels. Immunotherapy was received by 91.4% of patients, with Alectinib and Osimertinib being common. Grade III–IV pneumonitis occurred in 5.4% of patients. Conclusions: The study’s findings align with existing literature, highlighting significant smoking history, common adenocarcinoma, and substantial use of immunotherapy. Limitations include the observational design, small sample size, and short follow-up period, impacting the generalizability and long-term outcome assessment. Future research should address these limitations and explore longitudinal outcomes and emerging therapies.

Abstract PR012: A novel plasma-based epigenomic assay for comprehensive profiling of cancerous and inflammatory disease states

Abstract Background: We developed a method for comprehensive epigenomic profiling from 1 ml of patient (pt) plasma, targeting histone modifications and DNA methylation. This approach can be applied to plasma from pts with cancer and inflammatory conditions, allowing us to infer expression levels of diagnostic markers and drug targets, measure activity of therapeutically targetable transcription factors, and detect non-genomic mechanisms of resistance. By examining the transcriptional status of therapeutic gene targets and pathways, our method addresses the need for new approaches in liquid biopsy (LBx) assays, providing clinically actionable information that enhances the understanding of cancer and inflammatory biology and therapeutic response. Methods: We developed an innovative multimodal assay capable of revealing genome-wide transcriptional activity of promoters and enhancers from chromatin, as well as surveying the DNA methylome. Utilizing this assay on plasma samples from pts with 5 non- cancer conditions and 15 different tumor types, we generated comprehensive genome-wide transcriptional profiles across 21 conditions. Results: We identified transcriptional activation in cancer pt plasma of cancer-associated biomarkers (e.g., HER2, DLL3) in a tumor-specific manner and in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus/lupus nephritis. Epigenomic profiling simultaneously inferred the expression of multiple pertinent ADC and radio-immune targets (e.g., MET, HER2, HER3, TROP2, B7H4 in breast cancer and PSMA in prostate cancer), and SLFN11, a biomarker for sensitivity to these agents. The multimodal platform assesses transcriptional regulation genome-wide, enabling analysis of select genes as well as related pathways. For example, a multimodal classifier robustly predicted HER2 status across multiple HER2-expressing tumors. HER2 classification of breast cancer pts by epigenomic LBx was concordant with standard tissue-based IHC for 64/72 (89%) breast cancer samples (AUC 0.9). Accurate classification was achieved for 11/14 (79%) gastroesophageal adenocarcinoma and 4/4 (100%) ovarian cancer pts. A multi-modal predictive model trained on FOLH1 plasma epigenomic regulatory signals demonstrated significant accuracy in predicting quantitative readouts from PSMA PET scans (total SUVmean) in metastatic castration resistance prostate cancer pts and was associated with response to pluvicto. Epigenomic signatures also delineated activation of the endocrine signaling pathway in breast cancer and multiple mechanisms of resistance to androgen receptor signaling inhibition in prostate cancer, including reactivation of the androgen receptor, glucocorticoid signaling bypass, and histological transformation to a neuroendocrine subtype. Conclusions: This comprehensive epigenomic LBx assay offers a platform for simultaneous genome-wide transcriptional assessment of disease and therapy-relevant genes and pathways, marking a paradigm shift in our ability to assess the underlying transcriptional states of cancer and inflammatory diseases. Citation Format: Travis Clark, Anthony D'Ippolito, Aparna Gorthi, Jonathon Beagan, Jamey Guess, Amy Donahue, Mandy Greene, Alyssa Lau, Fernando Ramirez, Kristian Cibulskis, Jenna Wurster, Michael Coyne, Mary McGillicuddy, Baovy Tran, Tyrone Tamakloe, Hathairat Sawaengsri, Corrie Painter, Juliann Chmielecki, Geoff Otto, Matthew Eaton, Carl Barrett. A novel plasma-based epigenomic assay for comprehensive profiling of cancerous and inflammatory disease states [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR012.

Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures.

Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere. In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp). The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp. Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.

Abstract 4136926: Premature Ventricular Complexes and Nonsustained Ventricular Tachycardia in Cardiac Sarcoidosis

Introduction: The prevalence and prognostic significance of PVC and NSVT in cardiac sarcoidosis (CS), especially in patients with normal or mildly decreased LV function, are not well known and were investigated in the current study. Methods: We included 192 patients with definite and probable CS with LVEF>35%, no prior history of VT/VF or sudden cardiac death, who underwent up to 48 hours of Holter monitoring. They were followed retrospectively for the composite endpoint of sustained VT/VF, advanced heart failure therapy, and all-cause mortality. We performed multivariable analysis for the association of PVC burden and NSVT with the composite endpoint. Covariates were considered if they were present in at least 95% of the study sample and were significantly associated with the composite endpoint in univariable analysis. Results: The median PVC burden in the overall population was 0.3% (IQR 0.02-2.5%) and 36 (18.8%) patients had a PVC burden ≥5%. Sixty-two (32.3%) patients had NSVT detected during monitoring. The PVC burden and prevalence of NSVT in patient subgroups are shown in Figures 1 and 2. A total of 33 (17.2%) patients experienced one of the composite endpoints at a median follow-up of 3 years. In the multivariable analysis (Figure 3), PVC burden ≥5% versus <5% (HR 3.96 [1.19, 5.97], p-value <0.01) and presence of NSVT (HR 4.55 [2.09, 9.94], p-value <0.01) were associated with the composite outcome. Conclusion: Our results suggest that a high PVC burden and the presence of NSVT carry isolated prognostic value in CS. In addition, ventricular ectopy does not appear to be an indicator of disease activity based on abnormal uptake on PET scan.

Abstract 4136566: Primary Pericardial Mesothelioma: Diagnostic dilemma and rapid decline

Description of case: A 33-year-old man with no medical history or environment exposures, presented with dyspnea, nausea, and vomiting. He was tachycardic, with jugular venous distension, pulsus paradoxus, low voltage QRS and echocardiogram (TTE) showed a large pericardial effusion with ventricular interdependence. He underwent pericardiocentesis with negative fluid studies, including cytology. Two months later he represented with dyspnea and pleuritic chest pain, was diagnosed with pericarditis, and found to have recurrent pericardial effusion without tamponade. He was treated with aspirin and colchicine and discharged, with surveillance TTE showing a stable pericardial effusion but with significant adhesions and constrictive physiology (confirmed on right heart catheterization). Negative QuantiFERON was obtained and Anakinra started. Two months later he remained symptomatic with new pleural effusions and was sent for positron emission tomography scan which revealed diffuse intensely hypermetabolic pericardial thickening/fluid, up to 3.8 cm in maximal thickness and increased uptake in mediastinal nodes. Next, a cardiac MRI showed extensive circumferential thickening of the pericardial space approximately 2.5 cm in thickness. Both the visceral and parietal pericardium exhibited extensive scattered delayed hyperenhancement. Subsequent pericardial biopsy showed markedly fibrotic pericardium and pathology showed biphasic malignant pericardial mesothelioma. Immunosuppressive medications were stopped, and he underwent thoracentesis. After multidisciplinary discussions, he was started on nivolumab every two weeks and ipilimumab with a plan for surgery based on response to therapy. However, progressive symptoms and worsening constriction physiology led to palliative consultation and comfort care transition, with him dying shortly after. Discussion: Recurrent pericarditis and pericardial effusion, along with negative typical pericardial fluid studies, raised suspicion for a non-benign etiology. Multimodality imaging was employed and led to a pericardial biopsy. Constrictive pericarditis is an uncommon presentation of primary pericardial mesothelioma. Biphasic mesotheliomas from pleural or peritoneal origins are normally treated with systemic therapy with preference for combined immunotherapy. Primary pericardial mesothelioma is associated with a late presentation and high mortality rate, with surgery, if able to be done early appearing to be the recommended approach.

Abstract 4112639: A Rare Case of Atypical Sarcoidosis Presenting as an Intra-Atrial Septal Mass

Introduction: Sarcoidosis is a granulomatous disease that can affect multiple organ systems, including the heart. Cardiac Sarcoidosis (CS) is one of the most severe manifestations. It is characterized by a dysregulated T-cell driven immune response which generates non-necrotic inflammatory granulomas with myocardial infiltration. CS has a range of clinical syndromes: impaired conduction, arrhythmias, heart failure, and sudden cardiac death. We discuss a rare presentation of CS as an intra-atrial septal mass. Case Description: A 27-year-old Caucasian female with history of depression on citalopram presented with a one-month history of palpitations, fatigue, and dyspnea with exertion. An EKG demonstrated sinus rhythm with first-degree AV block. A cardiac monitor revealed intermittent 2-1 AV block and high degree AV block occurring mostly during sleep. An echocardiogram revealed normal biventricular function and morphology. Due to the concern for infiltrative cardiomyopathy, she underwent a cMRI which revealed a focal mass centered along the intra-atrial septum extending from the fossa ovalis to the septal AV junction, measuring 4.5 cm in size. She underwent pacemaker implantation with mild improvement of symptoms. PET scan demonstrated hypermetabolic activity of the intra-atrial region. She underwent surgical resection of the cardiac mass. Pathology was significant for fibrotic tissue with non-caseating granuloma and multinucleated giant cells consistent with an extremely rare presentation of CS. She was started on immunosuppressive medications. Subsequent cMRI and PET demonstrated resolution of the mass and hypermetabolic activity. Discussion: CS is a severe condition that most commonly presents with symptoms of heart failure, conduction abnormalities, and cardiac morphological changes of hypertrophy or thinning. However, it is often missed as a diagnosis, even in patients with extracardiac sarcoidosis. It is rare for CS to present as an isolated cardiac mass, especially in a younger patient as in this case. Advances in imaging techniques such as echocardiography, MRI, and PET have improved the ability to diagnosis CS and provide timely specialized treatment. This case highlights the need to include CS as an important diagnosis on the differential for a patient presenting with conduction abnormalities, heart block, and dyspnea. It also accentuates the critical role of multimodality imaging in working up this disease.

Feasibility of Using 18F-FDG PET/CT Radiomics and Machine Learning to Detect Drug-Induced Interstitial Lung Disease

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting and detecting DIILD are limited. Therefore, we aimed to evaluate the feasibility of 18F-FDG PET/CT, PET radiomics, and machine learning in distinguishing DIILD in an explorative pilot study. Methods: Eighteen Hodgkin’s lymphoma (HL) patients, of whom 10 developed DIILD after treatment with bleomycin, were retrospectively included. Five diffuse large B-cell lymphoma (DLBCL) patients were included as a control group since they were not treated with bleomycin. All patients underwent 18F-FDG PET/CT scans before (baseline) and during treatment (interim). Structural changes were assessed by changes in Hounsfield Units (HUs). The 18F-FDG PET scans were used to assess metabolic changes by examining the feasibility of 504 radiomics features, including the mean activity of the lungs (SUVmean). A Random Forest (RF) classifier evaluated the identification and prediction of DIILD based on PET radiomics features. Results: HL patients who developed DIILD showed a significant increase in standard SUV metrics (SUVmean; p = 0.012, median increase 37.4%), and in some regional PET radiomics features (texture strength; p = 0.009, median increase 101.6% and zone distance entropy; p = 0.019, median increase 18.5%), while this was not found in HL patients who did not develop DIILD and DLBCL patients. The RF classifier correctly identified DIILD in 72.2% of the patients and predicted the development of DIILD correctly in 50% of the patients. There were no significant differences in HUs over time within all three patient groups. Conclusions: Our explorative longitudinal pilot study suggests that certain regional 18F-FDG PET radiomics features can effectively identify DIILD in HL patients treated with bleomycin, as significant longitudinal increases were observed in SUVmean, texture strength, and zone distance entropy after the development of DIILD. The metabolic activity of these features did not significantly increase over time in DLBCL patients and HL patients who did not develop DIILD. This indicates that 18F-FDG PET radiomics, with and without machine learning, might serve as potential biomarkers for detecting DIILD.

Challenges in a Biological Definition of Alzheimer Disease.

It has been suggested that the diagnostic landscape of Alzheimer disease (AD) is undergoing a profound transformation, marked by a shift toward a biomarker-based approach, as proposed by the Revised Criteria for Diagnosis and Staging of Alzheimer's Disease. These criteria advocate for diagnosing AD solely on biomarkers, without requiring clinical symptoms. This article explores the drivers behind this transition, primarily influenced by the Food and Drug Administration's approval of amyloid-lowering treatments. We evaluate the proposed criteria, which allow for an AD diagnosis based on amyloid "A" or phosphorylated tau "T1" positivity through surrogate amyloid PET imaging, CSF, or plasma biomarkers, and consider the arguments for and against their use. The merits of the new criteria include a clearer definition of AD, which is currently used interchangeably to refer to both the presence of neuropathology and the clinical syndrome. We argue that a purely biological definition risks a category error and emphasize the need for longitudinal data to establish the lifetime risk of dementia in amyloid-positive and tau-positive individuals. We also caution against limiting the scope of biomarker-based AD diagnosis to amyloid and tau alone. In conclusion, we recommend that the criteria remain within the research domain for the present while advocating for the considered adoption of plasma biomarkers in clinical practice.

NIMG-24. PRECISION GLIOBLASTOMA MANAGEMENT USING MET AND FMISO PET SCANS

Abstract OBJECTIVE Positron Emission Tomography (PET) may be useful in diagnosing glioblastoma, determining resection areas, and evaluating therapeutic efficacy. This study evaluated the usefulness of PET scans using 11C-Methionine (MET) to assess amino acid metabolism and 18F-Fluoromisonidazole (FMISO) to assess hypoxic regions in glioblastoma treatment. METHODS Thirty glioblastoma patients who underwent MET and FMISO PET studies from July 2013 to March 2024 were included. Patients underwent the Stupp regimen post-tumor resection and were treated with temozolomide (TMZ) and bevacizumab (Bev) upon recurrence. PET scans were performed before and after two courses of Bev treatment. Changes in tumor to normal ratio (TNR) for MET, tumor to blood ratio (TBR) for FMISO, and metabolic tumor volume (MTV) for both MET and FMISO were evaluated. Progression-free survival (PFS) and overall survival (OS) were compared based on the rate of change in MTV for MET and FMISO. RESULTS The residual volumes (contrast-enhanced MRI, MET, and FMISO) with a MET removal rate of >90% were 0.08 ml, 0.1 ml, and 0.08 ml, respectively. For FMISO removal rates of >90%, residual volumes were 0.36 ml, 1.54 ml, and 0.05 ml, respectively. Groups with a decreased rate of change in MET MTV had significantly better outcomes: PFS (months) 10.7 vs. 2.8 (p=0.19) and OS (months) 18.6 vs. 4.9 (p=0.09). In the FMISO groups, decreased TBR change rates correlated with better outcomes: PFS (months) 16.6 vs. 2.5 (p<0.01) and OS (months) 22.8 vs. 4.9 (p<0.01). MTV change rates also showed significant differences in outcomes: PFS (months) 10.5 vs. 3.7 (p=0.76) and OS (months) 14.9 vs. 7.0 (p=0.87). CONCLUSION Higher MET removal rates correlate with fewer contrast-enhanced MRI and FMISO accumulation areas, suggesting MET as a reliable tumor removal indicator. Both MET and FMISO PET scans are valuable in determining glioblastoma treatment response.

NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR

Abstract BACKGROUND Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma. METHODS Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET. RESULTS Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET. DISCUSSION [68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.

NIMG-80. IMPACT OF KETOGENIC DIET ON MOLECULAR METABOLIC IMAGING WITH [18F]FDG AND [18F]DASA-23 POSITRON EMISSION TOMOGRAPHY IN A PATIENT WITH GLIOBLASTOMA

Abstract The standard-of-care for neuroimaging in patients with glioblastoma is contrast-enhanced MRI, which does not provide tumor metabolism information. Although [18F]FDG PET is used to image tumor metabolism in many solid organ cancers, it has limited benefit in atients with brain tumors due to the high level of glucose uptake in normal brain cells. [18F]DASA-23 is a novel PET radiotracer that assesses the levels of pyruvate kinase M2 (PKM2), a protein highly expressed in cancer cells, which undergo aberrant glycolysis. Despite [18F]DASA-23 having a higher tumor-to-background ratio (TBR) of standardized uptake values (SUVs) in the brain compared to [18F]FDG, both may be susceptible to altered carbohydrate metabolism in the setting of a ketogenic diet (KD). We report the case of a patient with glioblastoma on a KD, whose [18F]FDG and [18F]DASA-23 PET brain scans were limited in identifying disease progression (PD). Background was defined as the white matter contralateral to the tumor, at the level of the centrum semiovale, for TBR of SUVmax. A 39-year-old man was diagnosed with right temporal glioblastoma after previous diagnoses of grade 2 gliofibrillary oligodendroglioma (age 20) and grade 3 anaplastic oligodendroglioma (age 22). He began a KD after the glioblastoma diagnosis. 21 months later, TBR on [18F]DASA-23 PET was 1.38. One month later, surveillance brain MRI showed PD. Ten days later, TBR on [18F]FDG PET was 1.03. The patient died 15 months later. Despite MRI-based PD, the TBR of each radiotracer was not markedly elevated, although the [18F]DASA-23 TBR 1-month pre-PD was 34% greater than the [18F]FDG PET TBR 10-days post-PD. This may suggest a limitation of metabolic imaging by PET in the setting of a KD, and provide an opportunity to develop novel PET radiotracers that are not susceptible to the patient’s diet.

NIMG-10. THE ROLE OF FIBROBLAST ACTIVATION PROTEIN IN GLIOBLASTOMA AND GLIOSARCOMA – A COMPARISON OF TISSUE, 68GA-FAPI-46 POSITRON EMISSION TOMOGRAPHY AND SURVIVAL DATA

Abstract BACKGROUND Despite their unique histological features,gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast-activation-protein(FAP) is a component of a tumor-specific subpopulation of fibroblasts that play a critical role in tumor growth and invasion.However,the prognostic impact of FAP in glioblastoma and gliosarcoma is unclear. METHODS In a retrospective analysis,patients diagnosed with glioblastoma without sarcomatous differentiation and gliosarcoma were enrolled.Histological examination was performed using immunohistochemical FAP-staining and quantitative analysis with a standardized FAP-score.In a subset of patients,FAPI46-PET has been performed.The SUV-values are planned to be correlated with FAP-expression in the tumor tissue.Data obtained from immunohistochemical analysis and SUV-values are planned to be brought into perspective with clinically relevant prognostic factors,including survival estimates. RESULTS We enrolled 61 patients,including 13 diagnosed with gliosarcoma.Our analysis revealed that gliosarcomas exhibit significantly higher FAP-expression (median FAP-score: 3) compared to glioblastomas without sarcomatous differentiation (median FAP-score: 0.5, p<0.0001),where FAP was predominantly observed in the perivascular space.In gliosarcomas,FAP was also expressed by neoplastic cells.Moreover,a significant relationship was established between the immunohistochemical FAP-scores and the SUVmean and SUVpeak values on PET,suggesting that the PET tracer uptake accurately reflects the tumor’s FAP-expression.However,the differential expression of FAP suggests its potential as both a diagnostic marker and a therapeutic target.This hypothesis is further supported by the application of 68Ga-FAPI-46-PET in a 66-year-old female patient with recurrent gliosarcoma,alongside immunohistochemical analysis of tumor tissue.Both methods identified elevated FAP-expression and uptake,underscoring the feasibility of FAP as a target for nuclear medicine therapies in brain tumors. CONCLUSIONS Our study establishes a significant correlation between SUVmean/SUVpeak in 68Ga-FAPI-46 PET scans and FAP-expression in glioblastoma.Gliosarcomas express significantly more FAP than other glioblastomas. These insights suggest FAP’s potential as a theranostic target.We plan to investigate the effectiveness of FAP-specific tracers in treating recurrent gliosarcoma,aiming to open new therapeutic avenues.

DDEL-06. CONVECTION-ENHANCED DELIVERY OF SEVEN DIFFERENT MOLECULES SHOW LARGE DIFFERENCES IN CONVECTIVE PROPERTIES BETWEEN MOLECULES. INFORMED DECISION MAKING FOR OPTIMIZED CATHETER PLACEMENT AND SUBSEQUENT INFUSION STRATEGIES

Abstract INTRODUCTION Glioblastoma (GBM) trials based on convection-enhanced drug delivery (CED) bypassing the blood-brain barrier have failed to prove efficient until now. Many factors influence CED. In this study we evaluated CED of seven different molecules using dynamic PET/MRI during infusion. This enabled in-depth evaluation of drug distribution and concentration gradients providing a more precise understanding of the Vd/Vi ratio and the extent of efficacy level across the Vd zone. Novel surgical catheter placement software algorithms, results in more informed-decision-making for catheter positioning and subsequent infusion planning strategies. METHODS Pigs were implanted with neuroinfuse™ drug delivery systems enabling intermittent drug infusions. Gadolinium, [124I]-UdR, [55Co]Co-DOTA-hEGF, [55Co]Co-DOTA-SP4, [18F]PSMA-1007 and three differently sized [64Cu]-labelled nanocarriers were evaluated in both pigs with and without a brain resection cavity. Gadolinium distribution was followed by MRI. PET imaging was used for the rest. To inform clinical trial design, strategic catheter placement and volumes to be infused, planning was investigated on several historical GBM cases. RESULTS Vd/Vi ratios ranged between 1.00 – 3.77. where large-sized liposomes performed best. Catheters stayed patent during weeks of repeated infusions. In the resected animals no leakage of drugs into the brain resection cavity was observed. Effective 3D modelling of novel catheter infusion planning aids provided visualized representations of tailor-made infusion plumes, capable of being suitably positioned to optimize surgical planning of catheters and transcutaneous reaccess port. CONCLUSION Large differences in convective properties between different molecules were observed. Large-sized liposomes as drug-carrier system showed superior performance to all other molecules. Vd/Vi ratios for promising drugs should be determined before initiating future clinical CED trials. Infusion concentration gradients to facilitate more precise Vd/Vi ratios provided important performance metrics for visualised infusion planning aids of a novel chronic drug delivery system, illustrating informed decision making for optimised catheter placement and subsequent infusion strategies is clinically translatable for GBM indications.

IMMU-19. PRECLINICAL THERAPEUTIC ACTIVITY AND PET IMAGING OF STING AGONIST 8803 IN GLIOBLASTOMA

Abstract STING (stimulator of interferon genes) activation triggers interferon (IFN) release within the tumor microenvironment from myeloid cells and other cell types, inducing proinflammatory anti-tumor immune responses. The small molecule STING agonist, 8803, elicits long-term survival in 56% (QPP4; p=0.0003) to 100% (QPP8; p<0.0001) of mice with orthotopically implanted immune checkpoint-resistant glioblastoma models after 2-3 doses. In humanized mice, in which glioblastoma-cell STING is epigenetically silenced, 8803 therapeutic activity is maintained. The combination therapy of 8803 with anti-PD-1 relatively further enhances survival in immune checkpoint-resistant models. Ex vivo flow cytometry and proteomic sequential multiplex profiling during the therapeutic window demonstrate global immunological reprogramming, specific tumor-antigen immune responses, increased tumor immune effector trafficking, and release of IFN. It has been shown that IFN signaling augments intracellular nucleotide metabolism and increases [18F]-FLT uptake in pancreatic cancer. We evaluated the longitudinal [18F]-FLT uptake in CT-2A-bearing mice using MRI/PET/CT at days 0, 2, and 4 after intratumoral 8803 delivery. Brain images were acquired before and after [18F]-FLT tracer and 8803 administrations. The CT was used for PET attenuation/correction, and the MRI was used for tumor segmentation. Regional analysis of PET-derived [18F]-FLT SUV maps used advanced image processing approaches as a function of time to enhance the voxel-by-voxel interpretation of the acquired images. [18F]-FLT uptake increased from baseline in all mice treated with 8803 compared to control mice with a peak at 48-96 hours. Concordant sequential multiplex immunofluorescence demonstrated that the STING expression was prominent along the tumor vasculature, myeloid, and tumor cells. p-IRF-3 expression, reflective of STING pathway activation, showed a diffuse pattern after treatment. Based on the preclinical data, PET imaging at 48-96 hours post-treatment represents the appropriate imaging modality and timepoint to maximize the ability to detect STING-dependent changes for a therapeutic strategy that reprograms the glioblastoma microenvironment and improves survival across multiple preclinical models of glioblastoma.

NCMP-18. A CASE OF METASTATIC GLIOBLASTOMA MULTIFORME

Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor and rarely causes metastasis. We present a case of a 43-year-old female who developed tingling and heaviness in her right lower extremity in March 2023. This sensation progressed to involve her entire right hemi-body over the next two months. She presented to the emergency department where an MRI show a large left frontal parietal mass measuring 5.2x3.7x3.7cm with significant mass effect. She underwent surgical resection and surgical pathology showed IDH1-mutant R132H, retained ATRX, MGMT promoter mutation, and ki-67 of 80%. She received 6 weeks chemoradiation and then started maintenance temozolomide at 150mg/m2. Temozolomide was increased to 200mg/m2 for cycle 3 maintenance. In March 2024, she presented to the hospital with pain radiating down her legs and saddle anesthesia. MRI lumbar spine showed infiltrating osseous mass at S1 and S2 and bilateral sacral ala with anterior and posterior extraosseous invasion, invading the spinal canal resulting in moderate to severe spinal canal narrowing and compression of the sacral nerve roots. She underwent biopsy of the lesion which showed IDH wildtype metastatic GBM. She also underwent lumbar puncture and cerebrospinal fluid cytology was negative. She experienced pancytopenia limiting chemotherapy options. In April 2024, she underwent PET scan which showed hypermetabolic epidural soft tissue in spinal canal at L5-S1 level, widespread hypermetabolic skeletal lesions, tiny left cervical level 4 lymph node, small hypermetabolic right hilar, aortocaval, left retroperitoneal nodes and a tiny left common iliac node. The incidence of extracranial metastasis is 0.4-2.0% with less than 25 reported cases of bone marrow spread. This is thought to be rare due to the absence of lymphatics within the brain and the limited survival associated with GBM. This metastasis may occur through vascular invasion, perineural spread, lymphatics, direct invasion, or iatrogenic spread into soft tissues.

RADT-41. RADIOSURGERY FOR GLOMUS TUMORS: IMPACT OF MRI-PET FUSION ON TREATMENT PLANNING AND OUTCOMES

Abstract Paragangliomas present a challenge for stereotactic radiosurgery (SRS) treatment planning, particularly regarding the delineation of tumor boundaries. We propose that integrating 68Ga-DOTATATE PET scans alongside MRI in SRS planning will facilitate superior target identification and tumor coverage compared to reliance on MRI alone. A retrospective analysis of 9 patients diagnosed with paraganglioma who underwent MRI and 68Ga-DOTATATE PET imaging over a 20-month period was conducted. Images were imported into GammaPlan treatment planning software, partitioned into separate sessions: one with MRI and another with MRI-PET fusion. A single evaluator contoured paragangliomas as gross tumor volume (GTV) initially using MRI alone and subsequently with PET/MRI fusion. The pre- and post-PET fusion GTV volumes were compared. The standard deviation of the percentage increases in volume was calculated to assess variability across the sample. Of included 9 patients, 7 were females and median age was 58.3 years. Four patients had prior surgery. Seven patients were treated with Gamma Knife, while 2 with LINAC. Two patients were treated with single fraction SRS while 7 with hypofractionated SRS. Across all treated patients (n=9), GTV volumes significantly increased with PET fusion, with an average volume increase of 26.02% (n=8). One patient reported dryness of throat after SRS. Significant PET avidity over structures like temporal bone, internal jugular vein, petrous internal carotid artery and sigmoid sinus-IJV junction were included in PET/MRI fusion GTVs, which were missed on isolated MRI contours. At median 6-month follow up, all patients had a stable radiological response. Integration of 68Ga-DOTATATE PET scans with MRI enhances the visualization of paragangliomas in patients undergoing SRS. Further extensive studies are warranted to validate this observation and to better understand the variability in treatment response observed across the patient population. Our practice has initiated routine utilization of DOTATATE-PET imaging in paraganglioma patients undergoing SRS planning.