Decreased FDG Uptake Research Articles

Abstract PO4-20-10: Value of 16α-18F-fluoro-17β-fluoroestradiol PET imaging in ER-positive breast cancer: a case report

Abstract Introduction: An appropriate use criteria workgroup recently recommended the use of PET imaging utilizing the 16α-18F-fluoro-17β-fluoroestradiol (FES) radiotracer as a measure of disease progression and endocrine treatment response for ER-positive breast cancers. Past studies report limitations of decreased FDG uptake, the most common PET radiotracer, when measuring low Ki-67 scoring tumors; FES-PET may noninvasively address this shortcoming in FDG activity detection. Its benefit of detecting low-grade, ER-positive tumor activity was demonstrated in a patient with breast cancer who exhibited tumor growth only on FES-PET while FDG-PET showed no measurable disease. Clinical Case: A 57-year-old postmenopausal woman presented in December 2017 with de novo metastatic invasive ductal carcinoma that was ER+ (100%), PR+ (100%), and HER2- involving the right breast, bone, lungs, and internal mammary, subcarinal, and right hilar lymph nodes. She received nab-paclitaxel and radiation to the right breast, regional lymph nodes, and T11 bone. In March 2019, she underwent a right mastectomy with pathology that noted residual disease in the breast measuring <5 mm and was placed on exemestane in April 2019. She transferred her care to City of Hope and follow-up FDG-PET restaging showed no evidence of new metabolically active metastatic disease. Her cancer antigen 27.29 levels were also within normal limits. In the absence of measurable disease growth, she continued to be treated with single agent exemestane. Due to persistent back discomfort that she attributed to breast asymmetry, she requested the left breast to be removed. One week prior to surgery, both FDG-PET/CT and bloodwork inclusive of tumor markers were normal. She underwent a left mastectomy in March 2023. Pathology identified an incidental 1.4 cm lymph node in the 2000 g specimen that was ER+ (>95%), PR-, and HER2- with a Ki-67 of 1-3%. Somatic gene testing of the tumor revealed an ESR1 D538G mutation. As her progressive disease was not evident on previous FDG-PET imaging, an FES-PET/CT was performed and demonstrated uptake in the ilium, T10, and T12 bones that was not identified on FDG-PET/CT. With objective evidence of evaluable disease, exemestane was discontinued and fulvestrant and ribociclib were initiated. Clinically, she has evidence of early response to therapy with improvement in back pain. Discussion: This case demonstrates the value of FES-PET/CT in identifying disease that was not appreciated on FDG-PET/CT or by cancer antigen 27.29 monitoring. Additionally, ESR1 status has not been consistently reported in studies of patients undergoing FES-PET imaging that investigate the radiotracer’s value in predicting response to subsequent endocrine therapy. Our patient has a documented ESR1 mutation, her disease was clearly identified only on FES-PET/CT, and FES uptake predicted for response to subsequent endocrine therapy. Incorporating FES-PET in routine staging should be considered in patients with metastatic breast cancer that is low-grade and ER-positive. Further evidence of response prediction in patients with ESR1 mutations will enhance the utility of FES-PET in the clinical management of these patients. Citation Format: Megan Wong, Veronica Jones, Dave Yamauchi, Joanne Mortimer. Value of 16α-18F-fluoro-17β-fluoroestradiol PET imaging in ER-positive breast cancer: a case report [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-10.

Differentiating Brown Tumor From Bone Metastasis in Parathyroid Cancer Using 18 F-FDG PET and 99m Tc-MIBI SPECT.

A 69-year-old woman presented with a right clavicle pain. CT revealed a pathological fracture of the right clavicle, multiple osteolytic lesions, and a left cervical mass. 18 F-FDG PET/CT demonstrated a marked FDG uptake in the cervical mass and osteolytic lesions indicative of metastatic parathyroid cancer. 99m Tc-MIBI SPECT/CT revealed either faint or no uptake in the osteolytic lesions. However, a histopathological analysis after a parathyroidectomy and right clavicle biopsy confirmed the diagnosis of parathyroid cancer and the presence of benign brown tumors secondary to hyperparathyroidism. Postoperative imaging showed sclerotic change and a decreased FDG uptake in the bone lesions.

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

Comparison of Brain Amyloid Deposition and Cortical Glucose Metabolism Between Clinic- and Community-Based Cohort.

The differences in positron emission tomography (PET) imaging among older adults with mild cognitive impairment (MCI), according to the recruitment source, remain unclear. To investigate the differences in brain amyloid deposition and cortical glucose metabolism according to recruitment source among older adults with MCI. Participants in the clinic-based MCI cohort, who were referred to Oita University Hospital for cognitive decline, consisted of 90 adults with MCI. The community-based MCI cohort, which participated in a prospective cohort study, consisted of 118 adults with MCI. Participants underwent cognitive function evaluation, 11C-Pittsburgh compound B (PiB)-PET, and 18F-fluorodeoxyglucose (FDG)-PET. The prevalence of amyloid positivity and mean PiB and FDG uptake values were compared between the cohorts. Moreover, a voxel-by-voxel group study was performed to determine the areas with significant differences between the clinic- and community-based MCI cohorts. The prevalence of amyloid positivity and mean PiB uptake value in the clinic-based MCI cohort were significantly higher than those in the community-based MCI cohort (p < 0.001 and p < 0.001, respectively). The mean FDG uptake value in the clinic-based MCI cohort was significantly lower than that in the community-based MCI cohort (p < 0.001). SPM 8 analysis showed significantly increased PiB uptake in the precuneus and parietotemporal lobe and significantly decreased FDG uptake in the posterior cingulate in the clinic-based MCI cohort compared to the community-based MCI cohort. The prevalence and severity of amyloid pathology in older adults with MCI varied depending on the recruitment source.

Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study

BackgroundLenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes.ResultsThis was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078).ConclusionsThe therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC.Trial registration: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016.

Osteitis Fibrosa Cystica: An Unusual but Still Prevalent Manifestation of Uncontrolled Secondary Hyperparathyroidism

Abstract Background: Osteitis fibrosa cystica is an uncommon complication of untreated secondary hyperparathyroidism in patients with end-stage renal disease. The characteristic bony lesions that are seen in this condition very rarely can regress after medical treatment or parathyroidectomy. Clinical Case: A 65-year-old male with PMH of Systemic Lupus Erythematous (SLE) resulting in End-Stage Renal Disease (ESRD) on peritoneal dialysis (PD) and HTN, presented to his primary care physician for evaluation of a painful, enlarging lesion in his left forearm. The patient reported no history of trauma and denied having systemic symptoms. An X-Ray of his left forearm showed a lytic lesion within the proximal neck of the ulna, with erosion of the adjacent cortex. CT of the forearm showed a very vascular soft tissue mass causing significant erosive changes of the anterior cortex in the proximal ulna. Due to the characteristics of the lesion, an underlying malignancy was suspected as a possible diagnosis. The patient had a whole-body PET CT which showed multiple scattered hypermetabolic lytic osseous lesions throughout the axial and appendicular skeleton, including a large left proximal ulnar lesion. The patient had a bone biopsy from the lesion in his left ulna which showed a giant cell proliferation in a background of fibrosis and hemosiderin, suggestive of Osteitis Fibrosa Cystica (brown tumor of hyperparathyroidism). His laboratory workup around the time of the symptoms showed a normal serum calcium (9 mg/dl), associated with a high serum phosphorus (6.2 mg/dl), low vitamin D (20 ng/ml), and an elevated PTH (900 pg/ml). The patient was started on Cinacalcet, an increased dose of phosphate binders, as well as Calcitriol and the lesions and pain disappeared. Follow up lab work showed a normal Vitamin D (34 mg/dl), normal Phosphorus (4 mg/dl), and a PTH of 199 mg/dl, with a normal serum Calcium. A surveillance PET was performed 6 months after the initial one when the lesions clinically had disappeared and it showed again the presence of the bony lesions described prior, including the one in the left ulna, but with decreased FDG uptake, as well as new lesions in the spine. To date, the patient is asymptomatic and has not noted any new painful lesions. Conclusions: Osteitis fibrosa cystica remains a rare manifestation of secondary hyperparathyroidism, which may lead to an initial impression of malignancy. This patient exhibited clinical resolution of the painful symptoms associated with osteitis fibrosa cystica following medical management, though the lytic lesions involving the axial and appendicular skeleton persisted on surveillance imaging. This case serves as a reminder of the severe manifestations of a skeletal disease that has become rare given advances in early detection of and appropriate medical management of hyperparathyroidism.

(18F)-Fluorodeoxyglucose positron emission tomography/magnetic resonance imaging assessment of hypometabolism patterns in clinical phenotypes of suspected corticobasal degeneration.

Corticobasal degeneration (CBD) is a rare neurodegenerative disorder presenting with atypical parkinsonian symptoms that characteristically involves the frontoparietal region including the primary sensorimotor cortex, ipsilateral basal ganglia, and thalamus, typically in an asymmetric pattern. We aim to evaluate the metabolic and volumetric abnormalities in patients with clinically suspected CBD phenotypes utilizing hybrid 18F-fluorodeoxyglucose (FDG) positron emission tomography–magnetic resonance (PET/ MR) brain imaging. A retrospective analysis was performed on 75 patients (mean age 74 years, 31 males and 44 females) who underwent 18F-FDG PET/MR imaging (MRI) as part of their clinical dementia workup. Images were obtained using an integrated Siemens mMR 3T PET/MRI scanner. Two board-certified neuroradiologists and a nuclear medicine physician evaluated the metabolic and volumetric data of each hemisphere to assess for symmetric or asymmetric involvement of regions of interest in the subset of patients with suspected CBD. Of the 75 patients, 12 were diagnosed with suspected CBD based on a combination of clinical symptoms, neurocognitive testing, and hybrid neuroimaging findings. Ten of 12 patients (87%) demonstrated asymmetrically decreased FDG uptake involving a single cerebral hemisphere and ipsilateral subcortical structures, whereas two of 12 patients (13%) demonstrated striking hypometabolism of the bilateral sensorimotor cortices. Our study highlights two characteristic patterns of hypometabolism in patients with clinical and neuroimaging findings suggestive of the underlying CBD. The first pattern is asymmetric hypometabolism and volume loss, particularly within the frontoparietal and occipital cortices with involvement of ipsilateral subcortical structures, including the basal ganglia and thalamus. The second, more atypical pattern, is symmetric hypometabolism with striking involvement of the bilateral sensorimotor cortices.

English

BACKGROUND PET-CT is an imaging modality which electronically detects positron-emitting radiopharmaceuticals in the human body and reveals its exact anatomical location.1 PET CT measures the metabolic and functional activity of living tissue noninvasively.1 This technology is utilized in diagnosis, planning treatment and predicting outcomes in various neurological conditions.1 Depending upon various patterns of FDG uptake in different parts of brain, 18FDG PET-CT allows us to differentiate between various types of dementia.2 PET CT allows tracking the course of disease and revealing the severity of the disease.2 In this article, we discuss the imaging findings of normal 18 FDG PET-CT of brain and 8 different neurological conditions with their corresponding brain PET-CT findings. METHODS To study the role of 18FDG-PET/CT in neurological conditions, we identified 8 different patients who underwent 18FDG-PET/CT imaging of brain for clinically suspected different neurological diseases at Department of Radiodiagnosis-Centre of Excellence (CERIS), SRIHER, Chennai, between 2015 and 2019. Siemens Biograph Horizon 16-slice PET/CT scanner with TrueV was used. Syngo.Via Version VB30A software was used. 18F- Fluorodeoxyglucose was the radiotracer used [Dose: 3-7 mCi]. After the scan, different patterns of 18 FDG uptake in the brain were analyzed in each of these patients. RESULTS 18 FDG PET-CT showed reduced uptake in the epileptogenic foci in the brain. Alzheimer’s disease showed decreased FDG uptake in bilateral precuneus, posterior cingulate region, parietal cortex and frontal cortex. Fronto-temporal dementia revealed reduced FDG uptake in anterior cingulate gyrus and anterior temporal lobe. Primary progressive aphasia showed asymmetrical reduced metabolic activity in the bilateral frontal and temporal lobes. Progressive supranuclear palsy revealed reduced metabolic activity in bilateral paramedian frontal region, head of caudate nuclei and midbrain; Multi systemic atrophy showed reduced metabolic activity in midbrain, pons, medulla oblongata and the cerebellum; AIDS related dementia showed global hypometabolism with preserved uptake in basal ganglia. CONCLUSIONS 18FDG-PET/CT has a vital complementary role in the evaluation CNS disorders along with clinical examination, other imaging modalities like CT, MRI, and electroencephalogram (EEG). Radiologists should be aware of these different patterns of FDG uptake to aid the clinical diagnosis and early treatment. KEY WORDS 18 FDG PET-CT, 18FDG Uptake, Hypometabolism, PET-CT Brain

Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients.

Background and PurposeWe investigated 18F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis.MethodsThis study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA).ResultsTwenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension.ConclusionsStroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.

Association between the Onset of Idiopathic Normal Pressure Hydrocephalus Symptoms and Reduced Default Mode Network Connectivity

Objective: The aim was to examine the association between connectivity changes in the default mode network (DMN) and the progression of idiopathic normal pressure hydrocephalus (iNPH). Methods: We retrospectively recruited cases of preclinical and clinical iNPH from 2,196 patients who had received whole-body ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning. We included 31 cases with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM; reported as preclinical iNPH) and 12 with iNPH. We performed a voxel-based analysis of the brain FDG-PET images of the AVIM and iNPH groups as well as for each background-matched normal control (NC) group, using Statistical Parametric Mapping 12. Volume of interest (VOI)-based analysis was also performed. We set the VOI as the region from the precuneus to the posterior cingulate cortices (PCC), and compared the mean regional standardized uptake value ratio (SUVR) between the AVIM and iNPH group FDG-PET/CT images and each corresponding NC group. Results: The voxel-based analysis showed a greater decreased FDG uptake in the PCC in the iNPH group than in the AVIM group. The VOI-based analysis revealed no significant difference in the mean SUVR of the AVIM group and the corresponding NC group, but that of the iNPH group was significantly lower than that of its corresponding NC group. Conclusions: DMN connectivity was reduced in the clinical iNPH group but not in the preclinical group. These data suggest that alterations in the functional connectivity of the DMN are related to the onset of iNPH symptoms.

Detection of Residual Tumor With 68Ga-Pentixafor PET/CT in a Patient With Waldenström Macroglobulinemia and Concurrent John Cunningham Virus–Related Progressive Multifocal Leukoencephalopathy

A 75-year-old man diagnosed with Waldenström macroglobulinemia (WM) complained of neurological symptoms. Baseline F-FDG PET/CT showed diffusely increased radioactivity in the bone marrow and decreased FDG uptake in the right cerebellum. After rituximab-containing immunochemotherapy, the patient had clinically partial response of WM, but the cerebellar lesion was enlarged. Repeated F-FDG PET/CT was similar to the baseline. Ga-pentixafor PET/CT detected residual tumor of WM in occipital bone and cervical lymph nodes, but there was no uptake in the cerebellar lesion. Finally, John Cunningham virus-related progressive multifocal leukoencephalopathy was confirmed.

(18F)-Fluorodeoxyglucose positron emission tomography/magnetic resonance imaging assessment of hypometabolism patterns in clinical phenotypes of suspected corticobasal degeneration

Corticobasal degeneration (CBD) is a rare neurodegenerative disorder presenting with atypical parkinsonian symptoms that characteristically involves the frontoparietal region including the primary sensorimotor cortex, ipsilateral basal ganglia, and thalamus, typically in an asymmetric pattern. We aim to evaluate the metabolic and volumetric abnormalities in patients with clinically suspected CBD phenotypes utilizing hybrid 18F-fluorodeoxyglucose (FDG) positron emission tomography–magnetic resonance (PET/MR) brain imaging. A retrospective analysis was performed on 75 patients (mean age 74 years, 31 males and 44 females) who underwent 18F-FDG PET/MR imaging (MRI) as part of their clinical dementia workup. Images were obtained using an integrated Siemens mMR 3T PET/MRI scanner. Two board-certified neuroradiologists and a nuclear medicine physician evaluated the metabolic and volumetric data of each hemisphere to assess for symmetric or asymmetric involvement of regions of interest in the subset of patients with suspected CBD. Of the 75 patients, 12 were diagnosed with suspected CBD based on a combination of clinical symptoms, neurocognitive testing, and hybrid neuroimaging findings. Ten of 12 patients (87%) demonstrated asymmetrically decreased FDG uptake involving a single cerebral hemisphere and ipsilateral subcortical structures, whereas two of 12 patients (13%) demonstrated striking hypometabolism of the bilateral sensorimotor cortices. Our study highlights two characteristic patterns of hypometabolism in patients with clinical and neuroimaging findings suggestive of the underlying CBD. The first pattern is asymmetric hypometabolism and volume loss, particularly within the frontoparietal and occipital cortices with involvement of ipsilateral subcortical structures, including the basal ganglia and thalamus. The second, more atypical pattern, is symmetric hypometabolism with striking involvement of the bilateral sensorimotor cortices.

Sudden failure of ventricular pacing and recovery in a patient with cardiac sarcoidosis

A 76-year-old woman with sarcoidosis who had an implantable pacemaker for complete atrioventricular block was admitted with syncope. Electrocardiogram revealed ventricular pacing failure, and a marked rise in the ventricular pacing threshold. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) indicated increased uptake of FDG in the ventricular septum. Three days after steroid therapy, the ventricular pacing threshold reverted to normal, and FDG-PET showed decreased FDG uptake in the ventricular septum. In this case report, we demonstrate that a sudden deterioration in the ventricular pacing threshold due to worsening cardiac sarcoidosis can be reversed with early steroid therapy.

Abstract 3733: Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer

Abstract Objectives: 18F-fluorodeoxyglucose (FDG), an analogue of glucose, provides valuable functional information based on the increased glucose uptake and glycolysis in malignant tumor cells. Although both glucose transporter-1 (GLUT-1) and hexokinase2 (HK2) activity have been considered to associate with FDG uptake, the molecular mechanisms that determine FDG uptake are still largely unknown. Adenine nucleotide translocase 2 (ANT2) in the mitochondria inner membrane was reported to relate with tumor malignancy. We investigated the correlation between FDG uptake and Glut-1, HK2, and ANT2 expression in thyroid cancers throughout various spectrums of differentiation status. Methods: N-thy-ori (normal human thyroid cells), WRO (follicular cancer), BHP10-3 and TPC-1 (papillary cancer), and FRO (anaplastic cancer) were used for this research. GLUT-1, HK2, and ANT2 expressions were measured by western blot. ANT2 siRNAs and pcDNA3.1-ANT2 vectors were used to modify ANT2 expression. FDG uptakes were measured in thyroid cells and human embryonic kidney cells (293FT) with HK2 or ANT2 transfection. For patient tissue analysis, 95 thyroid tissue-array cores were evaluated, and which are classified 36 as normal, 44 as poorly differentiated (PD), and 15 as anaplastic thyroid cancer (ATC). ANT2 expression was measured by immunostaining, scored from 1 to 5. Results: FDG uptake in thyroid cancer cells was increased in anaplastic and poorly differentiated cells (P&amp;lt;0.001). GLUT-1 expression was higher in both TPC-1 and FRO than other cells. Whereas, HK2 was expressed only in cancer cells. ANT2 was expressed only in FRO cells and the highest FDG accumulation was also observed in FRO. ANT2 siRNA showed decreased FDG uptake (0.55-fold) and ANT2 overexpression increased FDG uptake (1.7-fold). In 293FT cells, HK2 and ANT2 transfection increased FDG uptake (P&amp;lt;0.01). PD tissues (mean = 41.7, SD = 19.7) and ATC (mean = 48.0, SD = 25.6) tissues from patients showed higher ANT2 expression than normal (P&amp;lt;0.05). Conclusion: We showed that ANT2 was expressed only in anaplastic thyroid cancer cells, and this was related to FDG uptake. Higher level of ANT2 expression was observed in dedifferentiated cancer, and this indicates that ANT2 can be used as a marker of malignancy in thyroid cancer. Citation Format: Chul-Hee Lee, Hyewon Youn, Seock-Jin Chung, Ha Kim, Cho Rong Park, Mi Jeong Kim, Young Joo Park, Sun Wook Cho, Keon Wook Kang, June-Key Chung. Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2017-3733

Preventive Effect of Rifampicin on Alzheimer Disease Needs at Least 450 mg Daily for 1 Year: An FDG-PET Follow-Up Study

Background: Rifampicin was reported to inhibit amyloid-β oligomerization and tau hyperphosphorylation in mouse models and could serve as a promising available medicine for the prevention of Alzheimer disease (AD). To examine whether rifampicin has such preventive effects in humans, we retrospectively reviewed ¹⁸F-FDG-PET findings of elderly patients with mycobacterium infection treated with rifampicin. Methods: Forty nondemented elderly patients treated with rifampicin for mycobacterium infections who showed AD-type hypometabolism were enrolled. The hypometabolic patterns were evaluated with stereotaxic statistical analysis and region of interest analysis. Results: Before treatment, AD-type hypometa bolism was observed in 12 patients. The FDG uptake in the posterior cingulate cortex (PCC) was improved or stabilized in 6 patients after 12-month therapy (450 mg/day), whereas another 6 patients with 6-month therapy showed a decreased FDG uptake in the PCC. In patients who underwent FDG-PET only after treatment, the metabolic decline in the PCC was significantly milder in patients with ≥12 months of rifampicin treatment than in those with 6 months of treatment. Multiple regression analysis revealed that the dose of rifampicin and treatment duration significantly influenced FDG uptake in the PCC. Conclusion: The preventive effect of rifampicin depended on the dose and the treatment duration, and the effect needs at least 450 mg daily for 1 year.

18F-FDG PET/CT evaluation of tumor response to the implantation of RENCA macrobeads (RMB) in phase I and II clinical trials [INDBB 10091] in advanced, treatment-resistant metastatic colorectal cancer (mCRC).

e15046 Background: RMB, a cytostatic, biological system form of anti cancer therapy have been used in Ph I &amp; II clinical trials in mCRC w/ evidence of improved survival benefit &amp; QOL. Evaluation of metastatic tumor response by standard CT RECIST criteria however has been unsatisfactory. We hypothesized that using 18F FDG PET/CT scan to evaluate tumor anatomy &amp; metabolism could provide a more accurate picture of tumor response to RMB Methods: 48 mCRC pts (14, Ph 1; 34, Ph 2a) who failed available treatments were implanted intraperitoneally w/ RMB (8mb/kg). Physicals, biomarkers &amp; lab evaluation were obtained at baseline &amp; days 14-90, with PET CT imaging at baseline &amp; day 90. PET scan was acquired 1 hour after FDG injection of 9.4 mCi. CT was used for attenuation correction. Correlation between 18F FDG PET SUVmax findings &amp; CEA &amp; or CA19-9 responses was assessed. Positive response was defined as ≥20% decrease post implant in CEA, CA19-9 &amp; SUV. Only tumors w/ SUVmax ≥ 2.5 were evaluated. SUV measurements were made by 1 radiologist experienced in PET-CT scanning &amp; SUV determination Results: 123 FDG positive mCRC lesions (39, Ph 1; 84 Ph 2a) were detected in 37 evaluable pts (14 m, 23 f; mean age 58.2; SUVmax 2.5-17.5). Of the 37 pts, 28 (76%) showed stabilization &amp; or decreased FDG uptake (4 w/ frank necrosis) as well as stable/decreased CT tumor measurements. Pts w/ pulmonary lesions showed greater responses than those w/ hepatic lesions. 9 (24%) of 37 pts showed increased SUVs. 23 pts (62%) showed decrease in CEA &amp; or CA 19-9 ≥ 20%. 17 pts (74%; 13 decrease, 4 central &amp; peripheral necrosis) had correlation between decreased SUVs/necrosis &amp; biomarkers decrease Conclusions: We conclude SUVs are useful in monitoring mCRC lesions response to RMB therapy. Changes in SUVs correlate w/ CEA &amp; CA 19-9 changes. Taken together the combined data indicate anti tumor effect in these Ph 1/2a trials &amp; offer preliminary support for our hypothesis that 18FDG can be useful in evaluating cell system therapies. Issues of SUVmax standardization &amp; effects of intra tumor heterogeneity however must be considered. Further studies are merited &amp; ongoing, including a planned Ph 3 trial Clinical trial information: NCT01053013; NCT00283075.

Pazopanib (PZP) in germ cell tumors (GCT) after chemotherapy (CT) failure: Final results of the open label, single-group, phase II Pazotest trial.

414 Background: Therapeutic options for patients (pts) with chemoresistant GCT are limited and prognosis is poor. PZP is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: In Pazotest trial (NCT01743482), pts were given PZP 800 mg/day until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based CT, including high-dose (HD)-CT. Baseline serum tumor markers (STM), computed tomography and FDG-PET were repeated after 4 wks and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-m PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, increasing size of nonteratomatous masses (RECIST v1.1), or the appearance of new lesions. Translational analyses included circulating IL8 levels and next generation sequencing of pre-PZP tissue from extreme responders. Results: 43 pts were enrolled from 05/2013 to 07/2016. 35 pts (81.4%) had nonseminoma, 6 (14%) primary mediastinal GCT. The number of failed CT regimen was: 2 (11.6%), 3 (51.2%), &gt; 3 (37.2%). 53.5% had failed HDCT. 39 pts had elevated STM: 56.4% AFP, 43.6% HCG. Grade 3-4 adverse events were seen in 4 pts (increased AST/ALT). 26/39 pts (66.7%) had STM reduction (38.5% &gt; 50% from baseline) after 4 wks. RECIST results: 1 partial response, 20 stable disease, 16 PD (6 not evaluable). 12 (27.9%) had a decreased FDG uptake. Median follow-up was 29.6 months. 3-m PFS was 12.8% (95%CI: 5.7-28.9), median PFS was 2.5 m (IQR: 1.0-3.0). 24-m OS was 14.2% (95%CI: 6.0-33.7). In pts with &gt; 50% STM decline, 24-m OS was 24.1% (95%CI: 8.3-69.6). Univariably, STM was associated with OS (HCG vs AFP: HR: 2.73, 95%CI: 1.24-6.02, p = 0.042). Baseline and +4wks IL8 levels did not predict for PFS/OS. In 2 responding pts, new mutations were found ( FLT3, G846V and RAD50 E448Q classified as damaging; TSC2, R197M and TNF A16V classified as benign). Conclusions: PZP was well tolerated and showed predictable activity, with early but short-living STM decline. Long term survival was obtained in a significant proportion of pts. Based on the present results, PZP may be investigated in earlier disease stages as an optimal bridging therapy preceding salvage curative treatment. Clinical trial information: NCT01743482.

A Case Series of Non-Hodgkin's Lymphoma Recurrence in Lower Extremities Mimicking Deep Vein Thrombosis

Background: While uncommon, non-Hodgkin's Lymphoma (NHL) can relapse in extranodal sites in the lower extremities. It is well established that venous thomboembolism occurs in higher incidence in patients with underlying malignancy. We describe 3 cases of NHL in which relapsed disease was discovered after lower extremity swelling prompted evaluation for deep vein thrombosis (DVT), and revealed recurrent NHL. CASE 1: A 61 YO F with history of Stage IEA Marginal Zone Lymphoma (MZL) of the dura diagnosed in 2012 received treatment with whole-brain and local brain radiation. In 2016 she developed recurrence in cervical lymph nodes. Six months after receiving 4 cycles of bendamustine and rituximab she developed left leg pain and calf swelling. PET/CT showed a hypermetabolic lesion in left tibia. MRI confirmed large lesion in mid-shaft of tibia extending down the length of the bone. CT-guided bone biopsy confirmed MZL. CASE 2: A 67 YO F with history of triple-negative inflammatory breast cancer treated in 2000 with neoadjuvant chemotherapy and mastectomy. PET/CT in 2008 showed 2 left femoral lesions. She underwent CT-guided bone biopsy of femoral lesion which confirmed follicular lymphoma (FL). Interim PET/CT in 2010 showed decreased FDG uptake in left femur. She was followed with watchful waiting. Then in 2014 patient developed leg swelling and pain, thought to be a DVT. Duplex ultrasound of the lower extremity was negative. PET/CT showed a left inguinal mass and left calf mass. MRI confirmed large mass within the left lower leg centered on the left fibular diaphysis with a very large associated soft tissue component with extensive muscular and neurovascular involvement. Biopsy of left inguinal lymph node confirmed diffuse large B-Cell lymphoma (DLBCL). CASE 3: A 61 YO M with history Stage IV FL in 1988 and initially treated with 4 cycles of PROMACE-CytaBOM. He relapsed nodally in 1995 and was treated on the IDEC investigational protocol with rituximab which led to a complete remission. In 2001 he developed a subcutaneous nodule on his back, biopsy showed FL, grade 1. A staging CT scan of neck, chest, abdomen, and pelvis was unremarkable, but a PET scan showed left axillary disease. He was re-treated with rituximab and local radiation which led to a complete response. Patient presented in 2008 with right calf swelling. Ultrasound at that time showed no DVT but confirmed swelling and suggested right inguinal adenopathy. PET/CT showed FDG uptake in multiple areas in groin and pelvis plus extensive uptake in thickened calf muscles extending from the right knee to the toe. Biopsy of right inguinal lymph node confirmed FL. Conclusion: Among NHLs, relapse patterns can vary significantly. Timing and frequency of relapse is largely dependent on whether NHL is classified as indolent or aggressive. However, location of relapsed disease in NHL is less well established. NHL relapse can occur in a fashion mimicking DVT with lower extremity swelling. When patients with history of NHL present with lower extremity swelling, relapsed disease should be included in the differential diagnosis. Table Patient characteristics Table. Patient characteristics Disclosures Cohen: Takeda Oncology: Honoraria; Pharmacyclics: Honoraria; Seattle Genetics: Honoraria; Amgen: Honoraria. Broome:True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

Clinical significance of dual-time-point 18F-FDG PET imaging in resectable non-small cell lung cancer.

ObjectiveThe maximal standardized uptake value (SUVmax) of pulmonary lesions on dual-time-point (DTP) fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for differentiation between malignant and non-malignant pulmonary lesions, and also to be of value for intrathoracic nodal staging of non-small cell lung cancer (NSCLC). However, a few NSCLC lesions have been found to show decreased FDG uptake on delayed images, and the significance of this finding remains unknown.Patients and methodsWe conducted a retrospective review of the data of 284 patients with NSCLC who underwent DTP FDG-PET before surgery. Cases of adenocarcinoma in situ and minimally invasive adenocarcinoma were excluded, because these lesions show little FDG uptake. Each patient was scanned at 60 min (early acquisition; SUV-E) and 115 min (delayed acquisition; SUV-D) after the radiopharmaceutical injection. The intratumoral retention index (RI) of 18F-FDG was measured for each examination by the DTP method. Recurrence-free survival (RFS) was determined by the Kaplan–Meier method and compared in relation to the SUV-E, SUV-D, and RI by univariate and multivariate analysis using models including the clinico-pathological prognostic factors.ResultsOf the 284 cases, the RI ≤ 0 was in 49 cases (17.3 %). This group of patients showed lower values of SUV-E and SUV-D, a smaller tumor size, and a lower rate of lymphatic invasion or vascular invasion. It was particularly noteworthy that lymph node metastasis was not histopathologically confirmed in any of these patients. Univariate analysis identified the RI, SUV-E and SUV-D, besides age, tumor size, lymph node metastasis, and tumor differentiation grade as predictors of the RFS. On the other hand, multivariate analysis identified the RI and lymph node metastasis, but not the SUV-E and SUV-D, as independent predictors of the RFS.ConclusionsThis study demonstrated that DTP FDG-PET of the primary tumor in NSCLC can be useful to predict the RFS of the patients. In addition, this method may also be useful to predict the presence/absence of intrathoracic lymph node metastasis in these patients.

PD7-03 IMPAIRED EXPRESSION AND FUNCTION OF TREK-1, A STRETCH-ACTIVATED TWO-PORE DOMAIN POTASSIUM CHANNEL, UNDERLIES DETRUSOR OVERACTIVITY IN HUMANS

INTRODUCTION AND OBJECTIVES: Afferent signals during bladder filling and voiding are important in lower urinary tract (LUT) function. The sensory cation channel transient receptor potential channel vanilloid 4 (TRPV4) is a key mediator in the generation of afferent signals towards the central nervous system (CNS). It has become possible to study this central neural control by means of positron emission tomography (PET) of the brain. We hypothetized that deletion of TRPV4 would influence brain control of the LUT by decreasing afferent input. METHODS: 12 Female Sprague-Dawley rats and 10 trpv4-/rats were used. Under urethane anesthesia a catheter was inserted in the bladder and the urethra was ligated. The animal was placed in a FOCUS 220 PET scan. The catheter was connected to a syringe pump and pressure transducer. Wild type and trpv4-/rats were equally divided into two conditions; an empty bladder condition, without infusion, and a full bladder condition, with infusion of saline until spontaneous contractions occurred. During cystometry, brain imaging was performed after injection of [18F]-FDG in the tail vein. For analysis PET images were normalized to a stereotactic space based on the rat brain Paxinos atlas using PMOD . We analysed on voxel basis using SPM8. RESULTS: In WT rats clusters of increased FDG uptake in the full bladder condition were observed in the insular, cingulate and posterior temporal cortex, while uptake was decreased in a cerebellar cluster (fig). Trpv4-/showed a different activation pattern during bladder fullness, with increased uptake in the orbitofrontal cortex and cerebellar peduncle. A cluster of decreased FDG uptake was also detected in the cerebellum. Wild type and trpv4-/rats showed differences in glucose uptake in the cerebellar and temporal cortex, thalamus, hypothalamus and hippocampus. CONCLUSIONS: In wild type rats a full bladder activated the insular and cingulate cortex. Both regions are key areas in the central neural control of the bladder; the insular cortex being the main endpoint for bladder afferent signals and the cingulate cortex the origin of motivation to void. This brain activation pattern was not seen in trpv4-/rats representing decreased afferent input into the CNS that contributes to a diminished motivation to void. Source of Funding: none