Reverse Warburg Effect-Related Mitochondrial Activity and 18 F-FDG Uptake in Invasive Ductal Carcinoma Abstract Purpose We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose (18F-FDG) uptake and mitochondrial activity in cancer cells and investigated the prognostic implications of this relationship in patients with invasive ductal carcinoma of the breast (IDCB). Methods One hundred forty-six patients with primary IDCB who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection were enrolled in the current study. Mitochondrial activity of cancer cells was assessed based on translocase of outer mitochondrial membrane 20 (TOMM20) expression and cytochrome C oxidase (COX) activity. A Pearson’s correlation analysis was used to assess the relationship between the maximum standardized uptake value of the primary tumour (pSUVmax) and mitochondrial activity. Clinicopathological factors, including pSUVmax, histological grade, oestrogen receptor (ER), progesterone receptor (PR), and TOMM20 expression; and COX activity, were assessed for the prediction of disease-free survival (DFS) using the Kaplan–Meier method and Cox proportional hazards model. Results Fourteen of the 146 subjects (9.6%) showed tumour recurrence. There was a significant positive correlation between 18F-FDG uptake and the mitochondrial activity of cancer cells in patients with IDCB, and increased 18F-FDG uptake and mitochondrial activity were significantly associated with a shorter DFS. Additionally, results from the receiver-operating curve analysis demonstrated that the cut-off values of pSUVmax, TOMM20 expression, and COX activity for the prediction of DFS were 7.76, 4, and 5, respectively. Further, results from the univariate analysis revealed that pSUVmax, TOMM20 expression, PR status, and histologic grade were significantly associated with DFS; however, the multivariate analysis revealed that only pSUVmax was associated with DFS (HR, 6.51; 95% CI, 1.91, 22.20; P = 0.003). Conclusions The assessment of preoperative 18F-FDG uptake and post-surgical mitochondrial activity may be used for the prediction of DFS in patients with IDCB.

Orbital IgG4 Disease: Imaging Findings on 68Ga-DOTANOC PET/CT Abstract Immunoglobulin G4 (IgG4)–related diseases are a spectrum of systemic inflammatory conditions of unknown etiology, which are characterized by infiltration of tissues by IgG4 plasma cells and sclerosing inflammation (Cheuk and Chan Adv Anat Pathol 17:303–32, 2010). Although this condition was initially described in relation to autoimmune pancreatitis, now it has been reported in almost every organ system of body (Zen and Nakanuma Am J Surg Pathol 34:1812–9, 2010, Masaki et al. Ann Rheuma Dis 68:1310–5, 2009). Orbital involvement by IgG4 disease can involve extraocular muscles (EOM), lacrimal glands, conjunctiva, eyelids, infraorbital nerve, orbital fat, and nasolacrimal system (McNab and McKelvie. Ophthal Plast Reconstr Surg 31:167–78, 2015, Katsura et al. Neuroradiology 54:873–82, 2012). The basis of using 68Ga-DOTANOC PET/CT in IgG4 orbital disease is the known expression of somatostatin receptors in chronic inflammatory cells (Cuccurullo et al. Indian J Radiol Imaging 27:509-16, 2017) and also avidity shown previously in other IgG4-related diseases (Cheng et al. Clin Nucl Med 43:773-6, 2018).

Pleuropericardial Cyst Mimicking a Metastasis of Differentiated Thyroid Carcinoma on Whole-Body Iodine-131 Scan: a Case Report Abstract Post-therapeutic whole-body scan (WBS) with I-131 has been widely used for the follow-up of patients with well-differentiated thyroid cancer (DTC). Although the sensitivity of WBS with I-131 in detection of functioning thyroid tissues is high, its specificity is low. So, a further evaluation is required in cases of unexpected findings. The purpose of the study was to demonstrate that awareness of the potential pitfalls of WBS in DTC, knowledge of physiology and characteristics of radioiodine uptake, and correlation with other imaging modalities are needed to avoid incorrect management of patients with DTC. This is a case report of a 49-year-old woman with an unexpected area of increased I-131 uptake in the posterior lower chest, which was finally diagnosed as a pleuropericardial cyst. Due to the false-positive uptake of I-131 in the chest, an accurate interpretation of the scintigraphic findings should be made.

Calf “Arch Sign” Seen on a Tc-99m-MDP Bone Scan Is Indicative of Synovial Fluid Leak in Ruptured Baker’s Cysts: Case Reports and Analysis of Literature Abstract The authors present two cases in which the ruptured popliteal (Baker’s) cysts remained undetected and were diagnosed only during an isotope investigation. The aim was to describe a specific imaging sign, the “arch sign”, that is indicative of ruptured Baker’s cysts. In both cases, the whole-body imaging was performed 2 hours after injection of 706.7 MBq of Tc-99m-MDP. Single-photon emission computed tomography (SPECT) imaging was performed to localize an accumulation of the radiopharmaceutical. An analysis of literature was performed to connect these cases with previously reported data and to detect the pathognomonic radio image sign of ruptured popliteal cysts. The arch-shaped distribution of the radiopharmaceutical below the knee joints was seen already on the whole-body bone scan image in both cases. An anterior view of SPECT MIP images showed the arched accumulation of the Tc-99m-MDP bone tracer along the postero-medial aspect of the right calf secondary to synovial fluid leak from a ruptured Baker’s cyst. The similar arthroscintigrams were published since 1971 without recognizing this sign as pathognomonic. Tc-99m-MDP bone scanning is sensitive for a Baker’s cyst with synovial effusion, and distribution of a radiopharmaceutical in the medial posterior calf in a shape of an arch, the arch sign, may serve as an indicator of a ruptured popliteal cyst.

Cerebral Amyloid Quantification in Cognitively Normal Korean Adults Using F-18 Florbetaben PET Abstract Purpose To investigate regional cerebral amyloid beta retention in cognitively normal Korean adults using F-18 florbetaben (FBB). Methods We prospectively analyzed F-18 FBB positron emission tomography (PET)/CT scans of 30 cognitively healthy adults (age range, 50–70 years) using automated quantification. The standardized uptake value ratios (SUVRs) of F-18 FBB were calculated for predefined regions by normalizing the regional count with cerebellar cortex. Results The distribution of amyloid beta for each brain region revealed no age-related trends (p > 0.05). From all subjects, mean SUVR of amyloid deposit was 1.30 ± 0.18. The right parietal lobe showed the highest SUVR value (1.46 ± 0.23), whereas the right frontal lobe and left precuneus showed the lowest SUVR (1.23 ± 0.25). Conclusions We provide reference values of normative data obtained from healthy elderly Koreans and suggest its use for accurate diagnosis of patients with Alzheimer’s disease.

Molecular Imaging in Breast Cancer Abstract Breast cancer (BC) is the most common cancer among females with more than 2 million new cases diagnosed worldwide in 2018. Although the prognosis in the majority of cases in the early stages combined with appropriate treatment is positive, there are still about 30% of patients who will develop locoregional diseases and distant metastases. Molecular imaging is very important in the diagnosis, staging, follow-up, and radiotherapy planning. Additionally, it is useful in characterizing lesions, prognosis, and therapy response in BC patients. Nuclear medicine imaging modalities (SPECT and PET) are of indispensable importance in diagnosis (positron emission mammography), staging (sentinel lymph node detection), and follow-up with18F-FDG and tumor characterization. Among many available PET tracers, the most commonly used are 18F-FLT, 18F-FES, 18F-FDHT, 64Cu DOTA trastuzumab (bevacizumab), 68Ga-PSMA, 68Ga-RM2 (gastrin-releasing peptide receptor), 18F-fluorooctreotide (SSTR), and 68Ga-TRAP (RGD)-3αvβ3-integrin. Molecular imaging helps in evaluation of tumor heterogeneity, allowing a shift from one-size-fits-all-approach to era of personalized medicine and precision oncology.

Debates over NICE Guideline Update: What Are the Roles of Nuclear Cardiology in the Initial Evaluation of Stable Chest Pain? Abstract Recent clinical trials have demonstrated the values of cardiac computed tomography (CT) in the initial evaluation of stable chest pain which led to drastic changes in the National Institute for Health and Care Excellence (NICE) guidelines in 2016. According to the updated NICE guidelines, cardiac CT should be performed as the initial cardiac testing in stable chest pain regardless of pre-test probability (PTP) of coronary artery disease (CAD). As a result, cardiac CT is now considered as a validated gatekeeper for assessing stable chest pain, which precedes all the functional studies including nuclear myocardial perfusion imaging (MPI). Nuclear MPI, in contrast, has been assigned as one of the second-line studies, which is inevitably dependent on the results of cardiac CT. However, nuclear MPI has genuine values in the diagnosis, treatment decision, and prognostic stratification of stable chest pain, which cannot be replaced by cardiac CT. In this review, the updated NICE guidelines and related cardiac CT trials will be critically reviewed from the view of nuclear physicians and the exceptional values of nuclear MPI will be described along with the future perspectives.

Correlation of Early-Phase F-18 Florapronal PET with F-18 FDG PET in Alzheimer’s Disease and Normal Brain Abstract Purpose F-18 florapronol (FPN) is the commercially recognized beta-amyloid positron emission tomography (PET) radiotracer in Korea. This study compared the early F-18 florapronol PET with F-18 fluorodeoxyglucose (FDG) PET between healthy controls (HC) and Alzheimer’s dementia (AD) patients. Methods A total of 29 subjects (15 HC and 14 AD subjects) underwent F-18 FPN PET and F-18 FDG PET. F-18 FDG PET image was acquired from 30 to 60 min and F-18 FPN PET for 0 to 10 min. F-18 FPN and F-18 FDG images were spatially normalized with transformation matrices obtained from individual CT images and standardized uptake value ration (SUVR) from cerebellum area, and the global mean was calculated using PMOD 3.6. Pearson’s correlation coefficients between F-18 FDG and early F-18 FPN for predefined cortical brain regions were calculated. Results We compared the F-18 FDG and F-18 FPN for SUVR of a specific region in global mean normalization and cerebellum normalization, and most of the correlation coefficient was higher in global mean normalization. In global mean normalization, the correlation coefficient for SUVR of HC was higher than that of AD in all brain regions. Conclusions Early F-18 FPN study can be used as a proxy marker for the F-18 FDG PET.

Amyloid PET Quantification Via End-to-End Training of a Deep Learning Abstract Purpose Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers. Methods Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method. Results The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PET and a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen’s kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively. Conclusion We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.

Postoperative Radioiodine Treatment within 9 Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma Abstract Purpose Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC. Material The analyzed group involved 701 DTC patients staged pT1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5–15.2). Results Based on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant. Conclusion If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.