Glioblastoma is a high-grade CNS neoplasm, which demonstrates resistance to the current forms of therapy and commonly recurs with poor prognosis. This mandates the call for diagnostic accuracy and development of new treatment strategies. Current literature provides strong evidence that F18-FLT PET, amino acid PET (with C11 MET, F18-FDOPA, F18-FET, F18-fluciclovine), PSMA PET, and FAPI PET imaging are more advantageous than F-18 FDG, demonstrating low background activity and high tumor-to-normal brain tissue ratio, promising for the early and accurate detection of GBM recurrence. The implementation of radiomics in the PET imaging interpretation has the potential to differentiate high-grade gliomas from low-grade gliomas. These PET radiotracers could also benefit in the assessment of treatment response and distinguishing tumor progression from treatment-related changes. The development of PET tracers assessing hypoxia is of considerable clinical value in the detection and management of treatment-resistant GBM. Further, PET imaging of the immune system provides significant insight into the evaluation of immune response to GBM and imaging PD-L1 expression. Additionally, there are promising targets for theranostics in the management of GBM. One especially promising target is PSMA, with Ga-68 PSMA PET for imaging and Lu-177 PSMA for systemically targeted radioimmunotherapry. The other potential target for theranostics in GBM is FAPI, using FAPI PET for imaging and Lu-177- labeled FAPI radiopharmaceuticals for therapy.

Background and Purpose: Paragangliomas (PGLs) are rare neuroendocrine tumors with imaging features that can overlap with other entities. This study hypothesizes that given overexpression of somatostatin receptor (SSTR) 2, PGLs can be differentiated on Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) from other benign or malignant lesions. Materials and Methods: Ninety-six patients with known tumors of the head and neck who underwent Ga-68 DOTATATE PET/CT from May 2017 to December 2021 were retrospectively reviewed from a single institution. Of these, 43 patients had histopathological confirmation and 66 positive lesions were discovered on PET/CT. For each lesion, the SUV max, the SUV lesion to liver ratio, and the SUV lesion to spleen ratio were analyzed. Results: PGLs (n = 37) showed the most intense uptake, and the mean of SUVmax was 69.3 (range 3.7–225.9). Metastatic PGL and metastasis from other neuroendocrine tumors (n = 13) demonstrated intermediate uptake, the mean of SUVmax was 15.16 (range 2.3–40.3). Meningiomas (n = 3) had intermediate uptake, and the mean of SUVmax was 12.37 (range 2.5–19.4). One patient with esthesioneuroblastoma had 5 lesions in the head and neck, and the mean of SUVmax was 18.9 (range 6.9–49.4). Schwannomas (n = 4) had very low uptake, and the mean of SUVmax was 1.75 (range 1.1–2.2). Other rare cases with low uptake included 1 each of osteosarcoma, acinic cell carcinoma, ectopic thyroid tissue, and plasmacytoma, and the mean of SUVmax was 4.75 (range 2.3–6.1). Conclusions: Ga-68 DOTATATE PET/CT can be a useful adjunct in differentiating tumors in the head and neck. PGLs demonstrate the highest uptake. Meningioma, esthesioneuroblastoma, and neuroendocrine tumor metastasis have intermediate uptake. Schwannomas and other rare tumors exhibit low uptake.

Since we are able to bring ionizing radiation in the form of a gas cloud to the respiratory system, we have wondered whether Xenon-133 inhalation could be exploited as a treatment option against Covid-19 respiratory virus infections, and urge colleagues in the scientific research community who have the capability to do so to explore the merits of using Xenon-133 in this way to determine whether its usefulness against the Covid-19 virus is indeed genuine.

BACKGROUND: Few studies have used hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) scan to identify degenerative facet disease. We aimed to determine the incidence of hypermetabolic facets on SPECT/CT imaging in patients with axial neck or back pain to elucidate the value of SPECT/CT scan in identifying pain generators. METHODS: A retrospective review of adult patients with axial neck or back pain was conducted. A total of 190 patients underwent high-resolution SPECT/CT imaging using a standardized protocol from January 2010 to April 2018. Facet joints with increased radionuclide uptake on SPECT imaging were characterized as hypermetabolic. Number, level, and laterality of hypermetabolic facets were recorded based on review of imaging and radiologist impressions. RESULTS: The average age of the patients was 58 +/- 13 years, and 51% of patients were men. A total of 85 patients (48%) demonstrated zygapophyseal joint hypermetabolism (ZJH) on SPECT imaging. A total of 202 hypermetabolic facets were identified, indicating the average number of facets with ZJH was 2.38 +/- 1.91. Of patients with a positive scan, lumbar facets were most commonly affected (69% of ZJH) followed by cervical (24%) and thoracic regions (6%). C1-2 and C2-3 (22% each of cervical ZJH) and L4-5 (32% of lumbar ZJH) were most commonly affected in the cervical and lumbar regions, respectively. CONCLUSIONS: Nearly half of all patients with axial neck or back pain demonstrated ZJH on SPECT/CT imaging, supporting ZJH sites as potential pain generators and targets for treatment. Our results support the role for SPECT/CT imaging in the workup of patients with axial neck or back pain, which may reduce invasive diagnostic procedures and aid in treatment planning.

1277 Objectives: Radium-223 dichloride (Ra-223 Xofigo) is a treatment option for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases. It is unclear whether a rising PSA during and after Xofigo therapy is due to bone and/or soft tissue disease progression or a flare response. To answer this question, this retrospective study evaluated alkaline phosphatase (ALP) and PSA levels, along with concomitant bone scan and CT observations. Methods: A total of 30 patients diagnosed with mCRPC with bone metastases were treated with Ra-223 dichloride between July 2014 and September 2019. Twenty-four of 30 patients had PSA assessment, ALP assessment, bone scan and CT chest, abdomen and pelvis acquired before the initiation of therapy as the baseline, between injections, and after finishing Xofigo therapy. Six patients were lost to follow-up after Xofigo therapy. Results: Among the 24 patients who had follow-up, 10 patients completed all 6 treatments of Xofigo, and 14 patients completed fewer treatments (between 1 and 5 cycles). On average, the ALP decreased by 29% at the nadir and 13% at completion, and the nadir occurred between the 3rd and 4th cycles. The PSA increased on average by 44% in between each cycle, and the lowest PSA was observed between the 1st and 2nd cycles. Three out of 24 patients (12.5%) PSA levels decreased after Xofigo therapy, and their ALP levels decreased or were stable after therapy. Two of these 3 patients had PSA flare phenomenon whereby the PSA increased initially after the 1st or 2nd cycles, and then decreased below baseline after the last treatment. Twenty-one out of 24 patients (87.5%) PSA levels increased during and after Xofigo therapy. Among these 21 patients whose PSA increased, 15 patients (71.4%) ALP levels were stable or decreased after completing therapy. The majority of these patients (11 out of 15) demonstrated soft tissue disease progression on CT scan, including metastases to the adrenal gland, liver, lung, lymph nodes or brain. The bone scans performed on these 15 patients showed variable responses, for example, 1 patient demonstrated improvement, 2 patients had stable bone scan findings, 4 patients showed mixed response (with some foci showing interval improvement and other foci demonstrating interval progression), and 8 patients demonstrated bone disease progression. Among the 21 patients whose PSA increased after therapy, 6 patients (28.6%) ALP levels increased, and their bone scans demonstrated progression (n=4) or mixed response (n=2). In addition, 5 of the 6 patients demonstrated soft tissue disease progression on CT with metastases to the adrenal gland, lung, liver, or lymph nodes. Conclusions: Most mCRPC patients (87.5%) in our study demonstrated increasing PSA levels during and after Ra-223 dichloride therapy. Despite a rising PSA, however, the majority (71.4%) of patients had ALP levels that were stable or decreased, and these patients were more likely to exhibit soft tissue disease progression on CT, with a variable response on bone scan. Patients with an increase in both PSA and ALP levels after Ra-223 dichloride therapy demonstrated disease progression in both the bones and soft tissues.

A 66-year-old man was diagnosed with metastatic prostate cancer to the bones. The patient started(223)Ra-dichloride (Xofigo) therapy in April 2019.Tc-99m-MDP bone scan and(18)F-fluciclovine (Axumin) PET/CT showed discordant but overall complementary findings that indicated disease progression after 5 doses of Xofigo therapy. The patient's prostate-specific antigen increased from 33.81 ng/mL at baseline before Xofigo therapy and up to 394.3 ng/mL after the fifth dose of Xofigo treatment. Because of disease progression, Xofigo therapy was discontinued.

OBJECTIVE:Hybrid SPECT with CT imaging has been used to help elucidate pain generators in patients with axial neck and back pain, identifying potential sites for treatment. Few studies have examined its role in spine surgery and most literature focuses on its use postoperatively. The authors describe the largest series to date of patients with symptomatic spondylosis who underwent preoperative SPECT imaging for surgical planning. METHODS:A retrospective medical and imaging record review was conducted to identify patients who underwent SPECT or SPECT/CT studies between January 2014 and May 2018. Patients who underwent spine surgical intervention for spondylosis with primary symptoms of axial neck or back pain and who had evidence of hypermetabolic foci on spinal SPECT imaging were included. Only those patients who subsequently underwent surgery on a spinal level associated with increased radiotracer uptake were included in the analysis. Patient baseline and demographic information, and data pertaining to SPECT imaging, surgical planning, and postoperative care were collected and analyzed. RESULTS:A total of 23 patients with an average age at surgery of 60.0 ± 11.0 years were included. Fifteen patients (65.2%) were male. A total of 53 spinal levels were treated, with an average of 2.30 levels treated per patient. All patients underwent fusion surgery, either lumbar (n = 14), with interbody fusion most commonly used (64.2%); or cervical (n = 9), with anterior cervical discectomy and fusion (66.6%) being the most common. The average length of hospital stay was 3.45 ± 2.32 days. One patient developed a wound infection postoperatively, requiring readmission. At the 3-month follow-up, 18 patients (78.3%) reported clinical improvement in pain. Eleven patients (47.8%) reported complete symptom resolution at the 6-month follow-up. At 1 year postoperatively, 19 patients (82.6%) reported significant relief of their symptoms following surgery. CONCLUSIONS:This is the largest series to date describing patients with axial neck and back pain who underwent preoperative SPECT imaging and subsequent surgical intervention on the affected spinal levels. The results demonstrate that SPECT imaging may be a useful adjunct to guide surgical planning, resulting in substantial clinical improvement following surgery.

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131I-meta-iodobenzylguanidine (HSA 131I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131I-MIBG. Conclusion: HSA 131I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

Objective: To evaluate the relationship between fatigue and cardiac sympathetic denervation in patients with Parkinson’s disease. Background: Fatigue represents one of the least understood non-motor manifestations of Parkinson Disease (PD). Decreased cardiac uptake of m-123I-iodobenzylguanidine (MIBG) was previously reported in PD patients. Cardiac sympathetic denervation seen in many patients with PD has been proposed as a possible mechanism for fatigue. Design and Methods: We recruited 10 PD patients with PD that reported symptoms of fatigue. Outcome measures included Fatigue Severity Score (FSS), Epworth Sleepiness Scale (ESS), Geriatric Depression Scale (GDS) and UPDRS. To quantify cardiac sympathetic denervation, patients underwent nuclear medicine Planar (early and delayed) SPECT scan with 123I-MIBG. Quantitative analysis was performed on the planar images by drawing regions of interest (ROIs) and calculating the Heart to Mediastinum ratio (H/M), as well as the washout ratio between early and delayed images. Results: Ten subjects with PD were enrolled and 8 completed the study. The mean age was 60 years (7 male, 3 female) with an average UPDRS score of 25.9 ± 8.5. The mean FSS was 3.9 ± 1.8. The mean early H/M ratio was 1.38 ± 0.16. Using a linear regression model, we did not find a significant correlation between the FSS score and the early H/M ratio (r2 = 0.26, F-statistic: 2.1 p-value: 0.20). Conclusion: In our sample we did not observe a significant relationship between measures of fatigue and cardiac denervation, as imaged using 123I-MIBG. Additional studies are needed to determine the causes of fatigue using more quantitative measures and larger sample size. Study Supported by GE Healthcare. Disclosure: Dr. Luca has nothing to disclose. Dr. Spengler has nothing to disclose. Dr. Georgiou has nothing to disclose. Dr. Serafini has nothing to disclose. Dr. Singer has received personal compensation for activities with Lundbeck Research USA, Inc., and Allergan, Inc. Dr. Singer has received research support from Allergan, Inc., Teva Neuroscience, and Ipsen.

1585 Background: Two types of adipose tissue exist: white adipose tissue (WAT) and BAT. WAT is the main energy store in humans and is associated with obesity and inflammation. BAT is thought to be protective against obesity and acts as an energy dissipating organ, which may fight obesity by reducing adipokines, inflammatory cytokines, and insulin resistance. The relationship of brown fat activation and cancer prognosis is unknown. We hypothesize that BAT may be protective to breast cancer patients by shifting glucose pool away from tumors and reducing tumor activity. Methods: Through a retrospective chart review of over 900 patients treated by the Breast Cancer Group at our institution, we identified 98 patients with BAT on PET CT scans. We collected information on patient demographics, lifestyle, staging and treatments received and response, progression of disease, overall survival, labs (lipids, hemoglobin A1C, Vitamin D, CRP), metabolic syndrome, metformin use, and antidepressants. Results: Of the 98 cases identified, 26 had Stage I disease at diagnosis, 32 had Stage II, 27 had Stage III, and 13 had Stage IV. The median age at diagnosis was 46. 62% of patients were Hispanic, 30% Caucasian, and 5% African-American. The majority of cases (86%) were of ductal histology. 77% were ER positive and 24% were HER2 positive. The median BMI of our cohort was 25.1. The 5 year PFS for our cohort was 74.6% (CI 64.2-82.4). The 5 year breast cancer specific OS was 94.2% (CI 86.6-97.6), with OS by stage showing I 100%, II 92.9% (CI 74.6- 98.2), III 91.7% (CI 70.5-97.9), and IV 92.3% (CI 56.6-99.0). While the total OS is within the range of 89.2% reported by SEER, our stage III and IV patients had a markedly improved OS compared to historical controls (41-67% and 15%, respectively, per ACS). Conclusions: To date, we have compiled the largest cohort of breast cancer patients with known BAT. While knowledge and clinical applicability of brown fat is still in its infancy, we hope that our study, with its remarkable OS for advanced stage disease, will shed light on the manner in which the presence of brown fat activation affects metabolism, treatment response, tumor microenvironment, and long-term prognosis.

Background: Marginal zone lymphomas (MZLs) account for 10% to 17% of all non-Hodgkin lymphomas (NHLs). Eradication of Helicobacter pylori (HP) is considered the initial therapy of choice for localized HP-positive gastric MALT and radiation is commonly used for other localized MALT or nodal MZL. While radiotherapy in localized MALT and nodal MZLs frequently results in long term local control and prolonged progression-free survival (PFS), it is not always feasible. Consensus guidelines on the best upfront therapy for patients with non-gastric MALT and disseminated extranodal MZLs are absent. Considering the excellent local control of MZLs with radiotherapy, targeted delivery of radiation by radioimmunotherapy may be the preferential approach for patients with untreated disseminated MZL. Based on this premise, we designed a single center Phase II clinical trial to examine 90Y Ibritumomab in the upfront treatment of patients with Marginal Zone Lymphoma.

1364 Learning Objectives 1. Learn about the classification, epidemiology, clinical presentation and risk factors of pancreatic cancers. 2. Review of anatomical localization, diagnostic imaging modalities and staging. 3. To become familiar with the appearance of pancreatic cancers using Somatostatin receptor scintigraphy SPECT/CT and F-18 FDG PET/CT and their usefulness and indication. 4. Discuss role of tumor markers such as CA19-9 and Chromogranin in correlation with imaging findings. Background: Pancreatic cancer, although infrequent, has an exceptionally high mortality rate. Surgical resection is the only potentially curative treatment, however, benefiting only a small group of patients due to late clinical presentation. Early and accurate diagnosis is essential for good prognosis. Therefore functional imaging has to play determinant role. Objective/Aim: A pictorial review in endocrine and exocrine pancreatic cancers was performed using a case collection from the University of Miami/ Sylvester cancer center, Miami - FL. The purpose is to review the literature and assess the usefulness and indications of Somatostatin receptor scintigraphy SPECT/CT and F-18 FDG PET/CT in diagnosing, staging and following post treatment response in pancreatic cancer. Content and Organization: 1. Review of classification, epidemiology, clinical presentation and risk factors of pancreatic cancers. 2. Review of diagnostic modalities and pictorial review of Somatostatin receptor scintigraphy SPECT/CT and F-18 FDG PET/CT correlated with conventional anatomical imaging. 3. Analysis of the usefulness and role that functional imaging can play in staging, diagnosis and post treatment response. 4. Illustration of most common findings and pitfalls in functional pancreatic imaging. 5. Association between imaging findings, including SUV values when applicable, histological diagnosis and tumor markers.

The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with with (90)yttrium (Y-90) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [Cl]: 65.6-97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients. With a median follow-up of 65.6 months (range 4.0-96.5), the median progression-free survival (PFS) was 47.6 months (range 4.0-93.3) and median overall survival (OS) was not reached. The 5-year PFS was 40% (90% CI: 19.9-59.5%) and 5-year OS was 71.8% (90% Cl: 46.8-86.5%). Overall, Y-90 ibritumomab tiuxetan was well tolerated and led to long-term responses and PFS rates.

1772 Objectives To develop and validate a semi-automated quantitative analysis program for DaTscan images to be used as an adjunct to visual assessment for differentiating between Parkinson9s disease (PD) and essential tremor (ET). Methods A semi-automated quantitative analysis program was developed that places manually drawn regions of interest (ROI) over the left and right putamen, left and right caudate, the entire striatum (putamen and caudate), as well as background on a composite transverse slice of attenuation-corrected SPECT images. The program calculates the binding uptake index for the striatum (SBI), putamen (PBI), and caudate (CBI), as well as putamen to caudate ratio (P/C) and striatum asymmetry index (SAI). The program was applied to 13 DaTscan patient SPECT/CT studies that were also independently assessed visually by two trained radiologists who ranked the images based on the level of uptake: 0-normal, 1-reduced uptake in one putamen, 2-reduced uptake bilaterally in the putamina, and 3-reduced uptake in the caudate. The intra- and inter-operator variability were also examined. Results There was good linear correlation (overall r=0.7) between the concordant classification of the distribution and uptake by visual assessment and that calculated by the program indices SBI, PBI, and CBI as well as P/C ratio. SAI was useful in determining uni- vs. bi-lateral reduction in uptake. Mean values and standard deviations were established for the various stages of uptake, though the patient sample was relatively small. Inter-operator variation was 2% and intra-operator 5% respectively, both of which were not found to be statistically significant based on student paired t-test (P>0.05). Conclusions A semi-automated quantitative analysis program for DaTscan images was developed that provides calculated indices reflecting the relative uptake in the striatum. This program can be a useful adjunct tool to visual assessment in classifying the levels of relative uptake in DaTscan images and in differentiating between PD and ET.