Clinical impact of quantitative [15O] H2O PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease.

BACKGROUND: This study was performed to determine the impact of oxygen-15-labeled water ([15O] H2O) positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) on referral for invasive coronary angiography (ICA) and revascularization. METHODS: This study involved 57 patients who underwent [15O] H2O PET/CT MPI for evaluation of coronary artery disease (CAD). Data of referral for ICA and revascularization, clinical symptoms, and cardiac events within 6 months after MPI were assessed. Logistic regression was used to determine the predictors for referral and revascularization. The diagnostic values of hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) were calculated. RESULTS: Normal and abnormal MPI findings were observed in 18 (32%) and 39 (68%) patients, respectively. The referral rate was significantly different between the normal and abnormal MPI groups (5.6% and 48.7%, respectively; P = .002). Revascularization rate of abnormal MPI group was 40.0%. There were significant differences of hyperemic MBF and CFR between patients with and without referral. Hyperemic MBF was significant predictor for referral (OR 15.24, 95% CI 3.39-68.55, P < .005) and revascularization (OR 28.57, 95% CI 3.08-265.33, P < .005). CONCLUSION: [15O] H2O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease.

Background: Some studies have reported the effectiveness of [18F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study's aim was to perform a semiquantitative analysis of [18F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30-75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis. Results: In the AD group, the occipital lobe had a significantly higher mean SUVr (1.46 ± 0.57) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus (1.06 ± 0.09 vs. 1.49 ± 0.86), inferior temporal (1.07 ± 0.07 vs. 1.46 ± 0.08), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences. Conclusion: A significantly higher mean SUVr of [18F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III-V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies.

Evaluation of Imaging Windows for Tau PET Imaging Using 18F-PI2620 in Cognitively Normal Individuals, Mild Cognitive Impairment, and Alzheimer's Disease Patients.

BACKGROUND: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients, using 18F-PI 2620 dynamic PET acquisition. METHODS: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic 18F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions. RESULTS: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of 18F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups. CONCLUSION: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

18F-FDG PET/Contrast-Enhanced CT for Initial Staging and Strategic Treatment of Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: Selection of the best treatment option for non-small cell lung cancer (NSCLC) depends on optimal initial staging. OBJECTIVE: Evaluate the clinical impact of 18F-FDG PET/CT on the management of Thai patients with NSCLC. MATERIAL AND METHOD: Twenty-four patients with NSCLC underwent FDG PET/CTfor initial staging. The best treatment options between pre- and post-FDG PET/CT staging were identified for each patient. Changes in treatment management decisions and the diagnostic values (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of nodal and distant metastases were assessed. RESULTS: Pre-FDG PET/CT staging included five patients with stage IA, four patients with stage IB, one patient with stage IIB, three patients with stage IIIA, and 11 patients with stage IV disease. A difference between pre- and post-FDG PET/CT staging was noted in 10/24 patients (41.7%). FDG PET/CT examination resulted in upstaging in 7/24 patients (29%) and downstaging in three patients (12.5%). The pre-FDG PET/CT staging was accurate in 14/24 patients (58.3%) while the post-FDG PET/CTstaging was accurate in 19/24 patients (79.2%). The treatment management decisions were changed in 5/24 patients (20.8%). FDG PET/CT prevented futile surgery in two patients. CONCLUSION: FDG PET/CT has an important role in NSCLC staging. Additional PET/CT information could influence therapeutic options and reduced unnecessary surgery in patients with metastatic disease.

The role of positron emission tomography-computed tomography/magnetic resonance imaging in the management of sarcoidosis patients.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The diagnosis is based on clinical and radiographic findings as well as by histopathological findings. Molecular imaging in recent years has made important progress regarding the study of various inflammatory diseases including sarcoidosis. Positron emission tomography (PET) provides an insight in metabolism of this disease. Positron emission tomography with fluorine-18-fluorodeoxyglucose ((18)F-FDG) has shown effectiveness in detecting occult disease and assessing disease activity during treatment. This review article provides an overview of the applications of PET/computed tomography and PET/ magnetic resonance imaging for evaluation of patients with sarcoidosis.

Pretherapeutic PSMA PET-Derived Semiquantitative Parameters as Predictors of PSA Response in Patients with mCRPC Receiving [ 177 Lu]Lu-PSMA-617 Radioligand Therapy.

Objective [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52-85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV ( p = 0.003), PSMA-TLU ( p = 0.013), and PSMA-TLQ ( p = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment ( r = -0.79, p = 0.006). No association was observed between PSMA-TV ( p = 0.367), PSMA-TLU ( p = 0.128), and PSMA-TLQ ( p = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT.

Head-to-head comparison of 18F-FDG and 18F-FES PET/CT for initial staging of ER-positive breast cancer patients.

PURPOSE: To compare the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoroestradiol (18F-FES) positron emission tomography/computed tomography (PET/CT) for initial staging of estrogen receptor (ER) positive breast cancer. METHODS: Twenty-eight patients with ER-positive breast cancer underwent 18F-FDG and 18F-FES PET/CT for initial staging. Diagnostic performance and concordance rates were analyzed for both radiotracers. Semiquantitative parameters of maximum standardized uptake value (SUVmax) and tumor-to-normal ratio (T/N ratio) were compared using Wilcoxon signed-rank test. Factors potentially affecting the degree of radiotracer uptake were analyzed by multi-level linear regression analysis. RESULTS: The overall diagnostic performance of 18F-FES was comparable to 18F-FDG, except for higher specificity and NPV, with sensitivity, specificity, PPV, NPV, and accuracy of 87.56%, 100%, 100%, 35.14%, and 88.35%, respectively, for 18F-FES and 83.94%, 30.77%, 94.74%, 11.43%, and 95.37%, respectively, for 18F-FDG. Diagnostic performance of strong ER expression was better in 18F-FES but worse for 18F-FDG. There was a correlation of mucinous cell type and Allred score 7-8 with 18F-FES uptake, with correlation coefficients of 26.65 (19.28, 34.02), 5.90 (- 0.005, 11.81), and p-value of < 0.001, 0.05, respectively. Meanwhile, luminal B and Ki-67 were related to 18F-FDG uptake, with correlation coefficients of 2.76 (1.10, 0.20), 0.11 (0.01, 0.2), and p-value of 0.018, 0.025, respectively. CONCLUSION: Diagnostic performance of 18F-FES is comparable to 18F-FDG, but better for strongly ER-positive breast cancer. Combination of 18F-FES and 18F-FDG would potentially overcome the limitations of each tracer with more accurate staging.

Intense 68Ga-FAPI-46 Activity in Lesions of Recurrent Ovarian Clear Cell Carcinoma That Were Negative on FDG PET/CT Study.

ABSTRACT: A 55-year-old woman with recurrent ovarian clear cell carcinoma who underwent complete surgical staging and completed chemotherapy session approximately 7 months before. She presented with increased CA-125 levels. 68Ga-FAPI-46 PET showed significantly higher tumor-to-background contrast of recurrent intra-abdominal node metastases and distant metastases, which were undetectable in the 18F-FDG PET. These findings changed the patient management. Larger studies with comparisons with other imaging modalities are required to validate the diagnostic performance.

Head-to-Head Comparison of 68Ga-FAPI-46 and 18F-FDG PET/CT for Evaluation of Head and Neck Squamous Cell Carcinoma: A Single-Center Exploratory Study.

68Ga-conjugated fibroblast activation protein inhibitor (68Ga-FAPI) has become an attractive agent for PET. This study aimed to compare 68Ga-FAPI-46 PET/CT with 18F-FDG PET/CT for detecting primary cancer and metastatic lesions in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Twelve patients and 28 patients with HNSCC underwent 68Ga-FAPI-46 and 18F-FDG PET/CT for initial staging and recurrence detection, respectively. The concordance and diagnostic accuracy of both tracers were analyzed. Semiquantitative parameters, including SUVmax, SUVmean, and tumor-to-background ratio, were compared. Fibroblast activation protein (FAP) expression tumor volume and total lesion FAP expression of 68Ga-FAPI-46 were compared with metabolic tumor volume and total lesion glycolysis of 18F-FDG, respectively. Differences between semiquantitative parameters were analyzed using paired t testing. Results:68Ga-FAPI-46 PET/CT was 83.3% and 96.4% concordant with 18F-FDG PET/CT for initial staging and recurrence detection, respectively. Eighteen lesions had histopathologic validation, and both tracers displayed 100% sensitivity, 50% specificity, and 94.4% accuracy for lesion-based analysis. FAP expression tumor volume was greater than metabolic tumor volume (P < 0.05), but no significant differences were observed for the other parameters. Conclusion:68Ga-FAPI-46 PET/CT showed good concordance with, and comparable diagnostic performance to, 18F-FDG PET/CT for initial staging and recurrence detection in HNSCC patients.

Comparisons of Quantitative Parameters of Ga-68-Labelled Fibroblast Activating Protein Inhibitor (FAPI) PET/CT and [18F]F-FDG PET/CT in Patients with Liver Malignancies.

PURPOSE: To compare quantitative parameters and tumour detection rates of [68 Ga]Ga-FAPI PET/CT with those of dedicated liver PET/MRI and 18F-FDG PET in patients with liver malignancies. PROCEDURES: Twenty-seven patients (29 imaging studies) with diagnosed or suspected liver malignancies who underwent [68 Ga]Ga-FAPI-46 PET/CT, liver PET/MRI, and [18F]FDG PET/CT between September 2020 and June 2021 were retrospectively analysed. MRI findings were used as the reference standard for diagnosis. RESULTS: The 27 patients had a median age of 68 years (interquartile range: 60-74 years; 21 men). Primary intrahepatic tumours were reported in 13 patients (15 imaging studies) with cholangiocarcinoma (CCA) and in 14 patients with hepatocellular carcinoma (HCC). All intrahepatic lesions detectable on MRI were also detected on [68 Ga]Ga-FAPI-46 PET/CT giving a sensitivity of 100% (19/19), whereas the sensitivity of [18F]FDG PET/CT was 58% (11/19). All intrahepatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT, on which they showed higher activity (median SUVmax: 15.61 vs. 5.17; P < .001) and higher target-to-background ratio (TBR; median, 15.90 vs. 1.69, P < .001) than on [18F]FDG, especially in patients with CCA (median TBR, 21.08 vs. 1.47, respectively; P < .001). The uptake positivity rate in regional node metastasis was 100% (12/12) on [68 Ga]Ga-FAPI-46 PET/CT compared with 58% (7/12) on [18F]FDG PET/CT. All patients with distant metastasis (100%, 14/14) were detected on both [18F]FDG and [68 Ga]Ga-FAPI-46 PET/CT imaging, although more distant metastatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT than on [18F]FDG (96% (42/44) vs. 89% (39/44), respectively). CONCLUSION: [68 Ga]Ga-FAPI PET/CT with dedicated liver PET/MRI shows potential for superior detection of hepatic malignancy compared with [18F]FDG PET/CT or MRI alone.

Alterations in 18F-FDG PET/MRI and 15O-Water PET Brain Findings in Patients With Neurological Symptoms After COVID-19 Vaccination: A Pilot Study.

PURPOSE: This study aimed to investigate functional abnormalities in the brain of patients with neurological adverse effects following COVID-19 (coronavirus disease 2019) vaccination using 18F-FDG PET/MRI and 15O-water PET. METHODS: Eight patients (1 man and 7 women, aged 26-47 years [median age, 36.5 years]) who experienced neurological symptoms after the first COVID-19 vaccination underwent CT, MRI, 18F-FDG PET/MRI, and 15O-water PET of the brain. After 7 days, each patient underwent a follow-up 18F-FDG PET/MRI and 15O-water PET of the brain. Imaging data were analyzed using visual and semiquantitative analyses, which included a cluster subtraction workflow (P = 0.05). RESULTS: There was no evidence of vascular abnormalities, acute infarction, or hemorrhage on the CT or MRI scans. On the 15O-water PET images, 1 patient had mildly significant decreases in perfusion in the bilateral thalamus and bilateral cerebellum, and another patient showed a diffuse increase in perfusion in the cerebral white matter. The visual and semiquantitative analyses showed hypometabolism in the bilateral parietal lobes in all 8 patients on both the first and follow-up 18F-FDG PET/MRI scans. Metabolic changes in the bilateral cuneus were also observed during the first visit; all patients exhibited neurological symptoms. Moreover, 6 patients showed hypometabolism, and 2 patients showed hypermetabolism. CONCLUSION: All regions of metabolic abnormality were part of the fear network model that has been implicated in anxiety. Our study findings support the concepts of and provide evidence for the immunization stress-related response and the biopsychosocial model.

Abnormality Pattern of F-18 FDG PET Whole Body with Functional MRI Brain in Post-Acute COVID-19.

Purpose: The study aimed to investigate imaging abnormalities associated with post-acute COVID-19 using F-18 FDG PET/CT and PET/ rsfMRI brain. Methods: We retrospectively recruited 13 patients with post-acute COVID-19. The post-acute COVID-19 symptoms and neuropsychiatric tests were performed before F-18 FDG PET/CT whole body with PET/rsfMRI brain. Qualitative and semiquantitative analyses were also conducted in both whole body and brain images. Results: Among the 13 patients, 8 (61.5%) had myositis, followed by 8 (61.5%) with vasculitis (mainly in the thoracic aorta), and 7 (53.8%) with lung abnormalities.. Interestingly, one patient with a very high serum RBD IgG antibody demonstrated diffuse myositis throughout the body which potentially associated with immune-mediated myositis. One patient experienced psoriasis exacerbation with autoimmune-mediated after COVID-19. Most patients had multiple areas of abnormal brain connectivity involving the frontal and parieto-temporo-occipital lobes, as well as the thalamus. Conclusion: The whole body F-18 FDG PET can be a potential tool to assess inflammatory process and support the hyperinflammatory etiology, mainly for lesions in skeletal muscle, vascular wall, and lung, as well as, multiple brain abnormalities in post-acute COVID-19. Nonetheless, further studies are recommended to confirm the results.

Comparison of performance between an F 18 -FDG PET normal brain template and a commercial template using the MIMneuro software.

Purpose: The aim of this study was to create and validate a normal brain template of F 18 -fluorodeoxyglucose ( F 18 - FDG ) uptake using the MIMneuro software to improve clinical practice. Approach: One hundred and nine volunteers underwent an F 18 - FDG positron emission tomography/computed tomography scan. Sixty-three participants with normal Alzheimer's disease (AD) biomarkers were used to create a template. A group of 23 participants with abnormal AD biomarkers and an additional group of 23 participants with normal AD biomarkers were used to validate the performance of the generated template. The MIMneuro software was used for the analysis and template creation. The performance of our newly created template was compared with that of the MIMneuro software template in the validation groups. Results were confirmed by visual analysis by nuclear medicine physicians. Results: Our created template provided higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV; 90%, 97.83%, 100%, and 100%, respectively) than did the MIMneuro template when using the positive validation group. Similarly, slightly higher performance was observed for our template than for the MIMneuro template in the negative validation group (the highest specificity and NPV were 100% and 100%, respectively). Conclusions: Our normal brain template for F 18 - FDG was shown to be clinically useful because it enabled more accurate discrimination between aging brain and patients with AD. Thus, the template may improve the accuracy of AD diagnoses.

11C-Pittsburgh compound B and 18F-THK 5351 positron emission tomography brain imaging in cognitively normal individuals.

Abnormal beta-amyloid plaques and tau protein accumulation are the core pathologic features of Alzheimer's disease. However, the accumulation of these proteins is also common in cognitively normal elderly people. Therefore, this study is aimed to evaluate the amyloid and tau accumulation in the cognitively normal population. A preliminary prospective study was conducted on 24 cognitively normal individuals who underwent Pittsburgh compound B (11C-PiB) and 18F-THK 5351 positron emission tomography (PET)/computed tomography scans. The standardized uptake value ratio (SUVR) was used for quantitative analysis of the two tracers and comparisons between two age groups: ≤60 years and >60 years. Co-registration was applied between the dynamic acquisition PET and T1-weighted magnetic resonance imaging to delineate various cortical regions. P-mod software with the automated anatomical labeling-merged atlas was employed to generate automatic volumes of interest for different brain regions. The posterior cingulate versus precuneus SUVRs of PiB uptake was 1.40 ± 0.07 and 1.38 ± 0.22 versus 1.17 ± 0.07 and 1.14 ± 0.18 in those aged ≤60 years and >60 years, respectively, whereas the SUVRs of THK5351 retention at brain stem versus inferior temporal SUVRs were 1.84 ± 0.06 and 1.91 ± 0.18 versus 1.37 ± 0.04 and 1.48 ± 0.21 in the age groups of ≤ 60 years and >60 years, respectively (P = 0.20). Our findings allow the determination of the preliminary optimal cutoff points for SUVRs in amyloid and tau PET studies. Ultimately, these values can be applied to normal databases in clinical use to improve quantitative analysis.

68Ga-FAPI-46 PET/MR Detects Recurrent Cholangiocarcinoma and Intraductal Papillary Mucinous Neoplasm in a Patient Showing Increasing CEA with Negative 18F-FDG PET/CT and Conventional CT.

A patient with intrahepatic cholangiocarcinoma who underwent hepatic resection with completed neoadjuvant chemotherapy presented with increased CEA levels. Previous whole abdominal and chest CT scan revealed no evidence of local recurrence or metastasis. 68 Ga-FAPI-46 PET showed significantly higher tumor-to-background contrast of recurrent tumor and nodal metastasis, which were undetectable in the FDG PET or conventional CT scan. These findings changed patient management. Larger studies with histopathological correlation and comparisons with other imaging modalities are required to validate the diagnostic performance. Moreover, a cystic lesion with FAPI uptake at the neck to the proximal body of the pancreas without FDG uptake is also incidentally noted. Differential diagnoses include sided branch IPMN and serous cystadenoma.

18F-THK 5351 and 11C-PiB PET of the Thai normal brain template.

OBJECTIVES: The aim of the study was to create a local normal database brain template of Thai individuals for 11C-Pittsburgh compound B (11C-PiB) and 18F-THK 5351 depositions using statistical parametric mapping (SPM) software, and to validate and optimize the established specific brain template for use in clinical practice with a highly reliability and reproducibility. METHODS: This prospective study was conducted in 24 healthy right-handed volunteers (13 men, 11 women; aged: 42-79 years) who underwent 18F-THK 5351 and 11C-PiB PET/CT scans. SPM was used for the 18F-THK 5351 and 11C-PiB PET/CT image analysis. All PET images were processed individually using Diffusion Tensor Image -Magnetic Resonance Imaging-weighted images (DTI-MRI images), which involved: (1) conversion of Digital Imaging and Communications in Medicine (DICOM) files into an analyzable file extension (.NIFTI) for statistical parametric mapping, (2) setting of the origin (the anterior commissure was used as the anatomical landmark), (3) re-alignment, (4) co-registration of PET with B0 (T1W) and DTI-MRI images, (5) normalization, and (6) normal verification using the Thai MRI standard. We then compared the normal PET template with the abnormal deposition area of different dementia syndromes, including Alzheimer's disease and progressive supranuclear palsy. RESULTS: This method was able to differentiate cognitively normal from Alzheimer's disease and progressive supranuclear palsy subjects. CONCLUSIONS: This normal brain template was able to be integrated into clinical practice and research using PET analyses at our center.

A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis.

Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment.