Positron Emission Tomography Radiopharmaceuticals in Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current hybrid scanner performing single photon emission tomography/computed tomography (SPECT/CT). Positron emission tomography/computed tomography (PET/CT) provides superior visualization and quantification of functions at the molecular level; thus, lesion assessment can be improved compared to that of SPECT/CT. Various types of cancer, including radioiodine-refractory DTC, can be detected by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most well-known and widely used PET radiopharmaceutical. Several other PET radiopharmaceuticals have been developed, although some are limited in availability despite their potential clinical utilizations. This article aims to summarize PET radiopharmaceuticals in DTC, focusing on molecular pathways and applications.

Risk-stratified papillary thyroid microcarcinoma: post-operative management and treatment outcome in a single center.

PURPOSE: This article aims to review and assess the post-operative management and treatment outcomes of papillary thyroid microcarcinoma (PTMC) in risk-stratified patients. METHODS: We retrospectively analyzed the data of PTMC patients who underwent thyroid surgery with or without radioactive iodine treatment (RAI) in a single center between January 2011 and December 2017. Demographic and clinicopathologic data were collected. Risk stratification according to the 2015 American Thyroid Association guideline was applied. RESULTS: Three hundred forty PTMC patients were included. Post-operative RAI was performed in 216/340 (63.53%) patients. In the non-RAI scenario, there were 122 low-risk and two intermediate-risk patients. In total, 261 (76.77%), 57 (16.76%), and 22 (6.47%) patients were classified as low, intermediate, and high risk, respectively. With a median follow-up time of 36 months (interquartile range: 23, 52), we found unfavorable outcomes (evidenced by imaging or out-of-range serum tumor marker levels: high thyroglobulin [Tg] or rising Tg antibody [TgAb] levels) in 8/340 (2.35%) patients, all of which received RAI. PTMC patients with unfavorable outcomes were stratified as low risk (4/261 [1.53%]), intermediate risk (1/57 [1.75%]), or high risk (3/22 [13.64%]). One death occurred in a patient with initial distant metastasis in the high-risk group. Initial high-risk stratification and initial stimulated Tg (of at least 10 ng/mL) were demonstrated as independent predictors for PTMC unfavorable outcomes (persistent or recurrent disease). Five patients with unfavorable outcomes (four with persistent disease and one with recurrent disease) had abnormal Tg or TgAb values despite unremarkable imaging findings. Moreover, 79/124 (63.71%) patients in the non-RAI scenario were only followed up with neck ultrasound. CONCLUSIONS: In general, at least 98% of low-risk and intermediate-risk PTMC patients showed favorable outcomes without persistent or recurrent disease, defined by either imaging or serum tumor markers. Nevertheless, aggressive disease could occur in few PTMC patients. Decisions on post-operative management and follow-up may be guided by initial high-risk stratification and initial stimulated Tg levels (≥10 ng/mL) as independent predictors for PTMC unfavorable outcomes. Monitoring using both imaging and serum tumor markers is crucial and should be implemented for patients with PTMC.

Cutaneous Management after Extravasation of High-Concentrated Amino Acid Solution Administered for Renal Protection in PRRT.

High-concentrated amino acid solution is used to protect the kidneys during peptide receptor radionuclide therapy (PPRT) in patients with neuroendocrine tumors (NETs). Extravasation of the solution can cause cutaneous complications. In this study, we described a 66-year-old man with metastatic medullary thyroid cancer and a 32-year-old woman with metastatic pancreatic NET who developed cutaneous lesions caused by the extravasation of an amino acid solution (25 g of lysine and 25 g of arginine in 1 L of normal saline) during PRRT with [177Lu]Lu-DOTA-TATE. Both were treated conservatively, and these cutaneous lesions gradually improved. The patient with metastatic pancreatic NET rejected the amino acid infusion in subsequent cycles of PRRT and therefore received [177Lu]Lu-DOTA-TATE alone, and her serum creatinine level and estimated glomerular filtration rate (eGFR) remained normal for 2 months after the last treatment. These two cases revealed cutaneous complications resulting from high-concentrated amino acid solution during PRRT because of hyperosmolarity. Health care providers should be aware of this complication to ensure its prevention and appropriate management. Preserved renal function was demonstrated after [177Lu]Lu-DOTA-TATE treatment in the absence of the infusion of a high-concentrated amino acid solution. However, long-term follow-up of renal function is suggested.

Myxedema Psychosis after Levothyroxine Withdrawal in Radioactive Iodine Treatment of Differentiated Thyroid Cancer: A Case Report.

Neuropsychiatric symptoms, especially acute psychosis (often referred to as myxedema madness or psychosis), are rare but possible clinical presentations of patients with hypothyroidism. A 42-year-old woman with papillary thyroid carcinoma and recent total thyroidectomy had developed flat affect, paranoid delusion, and visual and auditory hallucination during inpatient admission for elective radioactive iodine treatment. On admission, her history and physical exam did not reveal symptoms and signs of significant hypothyroidism. Other medical causes of acute psychosis were excluded, and the patient was immediately treated with thyroid hormone replacement therapy. Subsequently, her thyroid function normalized, and her psychotic symptoms gradually improved. Although there is a lack of classic signs and symptoms of hypothyroidism, myxedema madness should be recognized as one of the potentially treatable causes of acute psychosis.

Thai National Guideline for Nuclear Medicine Investigations in Epilepsy.

Epilepsy is a disorder of the brain, which is characterized by recurrent epileptic seizures. These patients are generally treated with antiepileptic drugs. However, more than 30% of the patients become medically intractable and undergo a series of investigations to define candidates for epilepsy surgery. Nuclear Medicine studies using Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) radiopharmaceuticals are among the investigations used for this purpose. Since available guidelines for the investigation of surgical candidates are not up-to-date, The Nuclear Medicine Society of Thailand, The Neurological Society of Thailand, The Royal College of Neurological Surgeons of Thailand, and The Thai Medical Physicist Society has collaborated to develop this Thai national guideline for Nuclear Medicine study in epilepsy. The guideline focuses on the use of brain perfusion SPECT and F-18 fluorodeoxyglucose PET (FDG-PET), the mainly used methods in day-to-day practice. This guideline aims for effective use of Nuclear Medicine investigations by referring physicians e.g. epileptologists and neurologists, radiologists, nuclear medicine physicians, medical physicists, nuclear medicine technologists and technicians.

Precision and Effects of a Small Meal on DXA-Derived Visceral Adipose Tissue, Appendicular Lean Mass, and Other Body Composition Estimates In Nonobese Elderly Men.

BACKGROUND: Information on precision errors and the least significant change (LSC) of dual energy X-ray absorptiometry (DXA)-derived body composition estimates is scarce, particularly for the appendicular lean mass (ALM) and appendicular lean mass index (ALMI). Overnight fasting is recommended for body composition measurements but has not been well tolerated by some elderly patients. This study aimed to establish precision errors and LSC values of body composition estimates in all regions-including visceral adipose tissue (VAT) and ALM-and the ALMI to assess the effect of a small meal on body composition and to estimate the changes it incurred. METHODOLOGY: Our institutional review board approved the study protocol. Altogether, 36 non-obese men aged ≥60 years, having given written informed consent, underwent body composition assessment after fasting overnight except for water. They underwent DXA scans three times, each time with repositioning (to simulate the clinical setting), the last after consuming a standardized meal (210-250 g and 200 cc of water). RESULTS: Precision errors and LSC values of DXA-derived body composition estimates in these elderly men tended to be higher than those in reports on younger subjects. Coefficients of variation (CVs (%)) of total bone mass (Tb.BMC) and total lean mass (Tb.LM) were <1%, whereas those of total fat mass (Tb.FM) and total %fat mass (Tb.%FM) were <2%, with LSCs of 45.8 g, 706.52 g, 731.4 g, and 1.15%, respectively. The CVs (LSC) of VAT, ALM, and ALMI were 8.9% (150.65 g), 0.93% (501 g), and 0.94% (0.19), respectively. After meal consumption, the mean changes in Tb.FM, Tb.BMC, and Tb.LM were -100, -8.2, and 440 g, respectively. CONCLUSIONS: Effects of a small meal on most parameters were trivial, including those for VAT, ALM, and ALMI, where changes were not statistically significant. None exceeded the LSC of ALM and ALMI, suggesting that a small meal is allowable before these measurements.

Cost-effectiveness analysis of epilepsy surgery in children and adolescents with drug resistant focal epilepsy at three years in a tertiary care epilepsy center in Thailand.

Epilepsy surgery is proven as a cost-effective treatment in developed countries, especially in adults with drug resistant epilepsy (DRE). This study is aimed to demonstrate the cost-effectiveness of epilepsy surgery in children and adolescents with DRE at three years compared with those who were eligible for surgery but received medical treatment. This study was conducted from January 2014 to December 2018. Clinical data were obtained from a retrospective chart review. Direct medical costs, including epilepsy surgery, inpatient and outpatient treatment were retrieved from the finance department. Direct non-medical costs were collected from the family interview. The effectiveness was determined by percent seizure reduction and quality of life assessed by EQ-5D scores. Decision tree analysis using TreeAge Pro® 2018 was deployed to determine the cost-effectiveness. Seventeen patients had epilepsy surgery and 19 were in the medical group. Seizure freedom was noted in 52% and 16% in the surgical and medical groups, respectively. Incremental cost-effectiveness ratio (ICER) was 743,040 THB (22,793 USD) per 1 QALY and 3302 THB (101 USD) per 1% seizure reduction. The study did not demonstrate cost-effectiveness of epilepsy surgery in the short term compared with Thailand's threshold (160,000 THB (4908 USD) per 1 QALY). Epilepsy surgery may be cost-effective if evaluated beyond three years.

PET/Computed Tomography in the Evaluation of Fever of Unknown Origin and Infectious/Inflammatory Disease in Pediatric Patients.

Fever in children is common. If it persists and its cause cannot be identified in a reasonable time, along with laboratory and conventional imaging investigations, it is defined as fever of unknown origin (FUO). 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is well established in the evaluation of malignancy, which is a possible cause of FUO. FDG often locates inflammatory and infectious lesions considered nonspecific or false-positive for oncology; however, these findings are beneficial in FUO evaluation because infectious and inflammatory diseases are important FUO causes. FDG-PET/CT is being increasingly used for investigation of FUO as well as infectious/inflammatory disease.

Incidental breast lesion detected by technetium-99m sestamibi scintigraphy in a patient with primary hyperparathyroidism.

Nuclear scintigraphy is functional imaging and can be combined with anatomical imaging to improve diagnostic yield. Detection of parathyroid lesion by technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) can facilitate an appropriate operative approach in a patients with primary hyperparathyroidism. Tc-99m MIBI is concentrated in highly cellular or metabolically active tissues, which have abundant mitochondria. False-positive scintigraphic findings could be from head-and-neck carcinomas, thyroid neoplasm, and multinodular goiter. In addition, multiple organs outside of the neck region, such as lung and breast, can take up the Tc-99m MIBI. Herein, we report the occurrence of abnormal focal uptake in the breast region during the preoperative localization of parathyroid adenoma and later discovered breast carcinoma.

Iodine-131 metaiodobenzylguanidine (131I-mIBG) treatment in relapsed/refractory neuroblastoma.

BACKGROUND: I-meta-iodo-benzylguanidine (I-mIBG) therapy has been used in treatment of for advanced neuroblastoma for many years with promising results. There are several studies regarding predictors and outcomes of I-mIBG therapies in relapsed/refractory neuroblastoma patients. OBJECTIVE: To identify the predictors and outcomes of I-mIBG treatment in relapsed/refractory neuroblastoma. METHODS: This study was a retrospective review of 22 patients with high risk stage IV relapsed/refractory neuroblastoma who received at least one cycle of I-mIBG therapy. Patient' characteristics, hematologic toxicity, scintigraphic semi-quantitative scoring, and overall survival were recorded. Factors predicting survival were analyzed. RESULTS: Twenty-two patients (50% male) with mean age of 3.7 years (4.8 months to 8.3 years) received I-mIBG therapies at an average of 3.8 and mean dose of 136 mCi (5032 MBq) per treatment. Most common acute hematologic toxicity was thrombocytopenia. Overall 5-year survival rate was 37% (95% confidence interval: 16.3-58.0) and median survival time was 2.8 year (95% confidence interval: 1.38-6.34). Patients with rising Curie score of ≥25% upon the second therapy were major determinants of overall survival with poorer response to treatment. At least three treatments of I-mIBG were needed to identify some degrees of survival prolongation (crude hazard ratio: P-value = 0.003). Age, sex, metastatic status, and baseline Curie scoring system were good predictors associated with survival. Seven patients (32%) demonstrated objective responses. CONCLUSION: Despite multimodality therapy, high risk neuroblastoma had a propensity of treatment failure in terms of relapsed or refractory, with some objective responses after I-mIBG treatments. The declined or non-rising Curie score upon second post-treatment total body scan was an important predictor of survival and aided a decision whether or not to proceed with bone marrow transplantation.

Errors in Patient Positioning for Bone Mineral Density Assessment by Dual X-Ray Absorptiometry: Effect of Technologist Retraining.

Improper positioning is one of the factors that can lead to incorrect bone mineral density (BMD) results. This study aimed to assess the frequencies of erroneous positioning during three periods: before retraining of the technologists (BR), after retraining (AR), and at the current timepoint 8 years after retraining (C). The BMD images of the first 150 consecutive patients who underwent DXA of the lumbar spine and hip during each of the three periods were retrospectively reviewed. Patients were excluded if they had severe scoliosis, rendering proper positioning impossible. Each BMD image was assessed by an International Society of Clinical Densitometry certified clinical densitometrist who was blinded to the date of the initial examination. For the lumbar spine in the BR group, the criteria frequently not met were inclusion of both iliac crests (33.8%), straightness (30.3%), and midline positioning (20.4%); the respective frequencies were significantly reduced to 0.8%-5.6%, 2.1%-3.0%, and 0%-2.8% in the AR and C groups (p < 0.05). For the hip in the BR group, the criteria frequently not met were straightness (52.8%) and internal rotation (21.8%); the respective frequencies were significantly reduced to 0%-4.2% and 8.3%-8.4% in the AR and C groups (p < 0.05). Overall improper positioning in the BR group was 49.3% and 57.3% at the lumbar spine and the hip, respectively; the respective frequencies were reduced to 9.3% and 12.7% in the AR group, and to 2.7% and 7.3% in the C group. The least significant change values for the lumbar spine, femoral neck, and total hip also became smaller after retraining. Retraining the technologists improved patient positioning, as evidenced by the decreased frequencies of erroneous positioning and the improved least significant change values after the retraining.

Simulated increased soft tissue thickness artefactually decreases trabecular bone score: a phantom study.

BACKGROUND: Trabecular bone score (TBS), which has been proposed to be used in complementary with bone mineral density (BMD) to improve the assessment of fracture risk, is negatively associated with body mass index (BMI). The effect of soft tissue, which is expected to be thicker in subjects with high BMI, on TBS was studied using three scan types: Hologic with fast array mode (Hfa), Hologic with high definition mode (Hhd), and GE-Lunar iDXA. METHODS: A spine phantom provided by Hologic for routine quality control procedure was scanned using three scan types: Hfa, Hhd, and iDXA. The phantom was scanned with an overlying soft tissue equivalent material (bolus used in radiotherapy) of 0 (without), 1, 2.5, 3.5, 5 and 7.5 cm thick. For each setting, 30 acquisitions were performed in the same way as for the quality control procedure. TBS was calculated using TBS iNsight® software version 2.1 on the same regions of interest as those used for lumbar spine BMD. RESULTS: Mean ± SD TBS of the phantom (without overlying soft tissue) were 1.379 ± 0.018, 1.430 ± 0.009, and 1.423 ± 0.005 using Hfa, Hhd, and iDXA, respectively. A one-way repeated measures ANOVA showed that there were statistically differences in TBS due to different thicknesses of soft tissue equivalent materials for all three scan types (p < 0.001). A Tukey post-hoc test revealed that the decrease in TBS was statistically significant (p < 0.001) when the soft tissue thickness was 1 cm (-0.0246 ± 0.0044, -0.0319 ± 0.0036, and -0.0552 ± 0.0015 for Hfa, Hhd, and iDXA, respectively). Although to a lesser degree, the effects were also statistically significant for BMD (p < 0.05): an increase for Hfa and Hhd but a decrease for iDXA. However, these changes did not exceed the least significant change (LSC) derived from patients. CONCLUSIONS: Increased soft tissue thickness results in lower TBS value. Although BMD is also affected, it is unlikely to pose a clinical problem because the change is unlikely to exceed the patient-derived LSC.

Incidental Gallbladder Cancer Visualized From Posttreatment 131I Whole-Body Scan.

A 72-year-old woman with papillary thyroid cancer post-total thyroidectomy was referred for post-I treatment whole-body scan. Images revealed focal uptake within the gallbladder. Cholecystectomy was subsequently performed, and the pathology report showed well-differentiated adenocarcinoma. Given a history of papillary thyroid cancer, the iodine uptake was reasonably explained as metastasis; however, gallbladder metastasis was extremely infrequent. Literature described the incidental radioiodine retention in the gallbladder as false-positive findings, which can be normal variants or benign hepatobiliary conditions. Primary gallbladder malignancy could be counted for another possibility despite controversial mechanism of uptake.

Factors affecting disease-free status of differentiated thyroid carcinoma patients.

PURPOSE: The study aim was to assess factors that impact on the outcome of radioiodine therapy in patients diagnosed with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: We performed a retrospective cohort study on 256 patients with DTC who underwent thyroidectomy and received radioiodine therapy during December 2003 to January 2012. All patients were followed up for at least 1 year. They were considered disease- free by the criteria of the revised American Thyroid Association Management Guideline for Patients with Thyroid nodules and DTC (ATA guideline 2009). RESULTS: On Cox univariate analysis, factors associated with disease-free status were age<45, stage I tumor, low risk group by histopathology, unifocal tumor involvement, stimulated serum Tg level at 1st dose of radioiodine therapy and no distant metastasis from 1st post-treatment WBS (post RxWBS). On multivariate analysis, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy<30 ng/mL were the significant prognostic factors that increased disease-free rate by 1.73 times and 2.60 times, respectively (P-value<0.05). CONCLUSIONS: Factors affecting the outcome of radioiodine therapy in our study were age, stage, risk of recurrence by histopathology, unifocal tumor involvement and 1st postRxWBS findings. From these factors, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy were independent prognostic factors that substantial increase the disease-free rate.

Unexpectedly expected fetal thyroid function on posttreated radioiodine (131I) SPECT/CT of a patient with differentiated thyroid cancer.

We present a 25-year-old woman who has a diagnosis of differentiated thyroid cancer, a 2.5-cm papillary carcinoma in the right lobe, and presence of minimal extrathyroid invasion. 131I ablation and/or treatment of 150 mCi was given orally 3 months after total thyroidectomy. A fetus with radioiodine uptake in the fetal thyroid was unsuspectedly detected by SPECT/CT after 131I treatment.

131I-rituximab treatment in patient with relapsed non-Hodgkin's lymphoma: the first case report in Thailand.

Radioimmunotherapy (RIT) with 131-rituximab is a safe and effective treatment in patients with relapsed, refractory follicular lymphoma. The authors demonstrated the first case of 131-rituximab treatment in the patient with relapsed non-Hodgkin's lymphoma (NHL) in Thailand. There was no immediate complication after treatment. Impressive treatment response occurred.

PET imaging of high-affinity α4ß2 nicotinic acetylcholine receptors in humans with 18F-AZAN, a radioligand with optimal brain kinetics.

UNLABELLED: We evaluated (-)-2-(6-[(18)F]fluoro-2,3'-bipyridin-5'-yl)-7-methyl-7-aza-bicyclo[2.2.1]heptane ((18)F-AZAN), a novel radiotracer that binds to α4ß2 nicotinic acetylcholine receptors (α4ß2-nAChRs) and shows high specific binding and rapid and reversible kinetics in the baboon and human brain. METHODS: We tested safety tolerability and test-retest reliability (n = 5) and proposed initial quantification of (18)F-AZAN receptors in 3 healthy human subjects who had nicotine exposure and 9 who did not. We also present a receptor blocking study in a nicotine subject dosed with the α4ß2-nAChR-selective partial agonist varenicline. RESULTS: Radiation dosimetry PET/CT experiments indicated that most human organs received doses between 0.008 and 0.015 mSv/MBq, with an effective dose of approximately 0.014 mSv/MBq. The tracer rapidly entered the brain, and the peak was reached before 20 min, even for thalamus. Ninety-minute scans were sufficient for (18)F-AZAN to obtain the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue (BPND) using plasma reference graphical analysis, which showed excellent reproducibility of BPND (test-retest variability < 10%) in the nAChR-rich brain regions. Regional plasma reference graphical analysis BP(ND) values exceeded 2 in the midbrain tegmental nuclei, lateral geniculate body, and thalamus for nonsmokers (n = 9) but were less than 1 in the nAChR-poor brain regions. There was a dramatic reduction of (18)F-AZAN brain uptake in smokers and varenicline-treated subjects. CONCLUSION: (18)F-AZAN is a highly specific, safe, and effective PET radioligand for human subjects that requires only 90 min of PET scanning to estimate high-affinity α4ß2-nAChR in the living human brain.

18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry.

UNLABELLED: Identification of safe and valid PET radioligands for metabotropic glutamate receptor, type 5 (mGluR5), is essential to measure changes in brain mGluR5 in neuropsychiatric disorders, to confirm central mGluR5 occupancy of drug candidates, and to guide dose selection for obtaining an optimum therapeutic window. Here we present the results of a first-in-human study assessing the safety and effectiveness of a novel PET radiopharmaceutical, (18)F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ((18)F-FPEB), for quantifying regional brain concentrations of mGluR5. METHODS: Quantification of whole-body biokinetics was conducted in 6 healthy adults (3 men and 3 women). The radiation safety profile was estimated with OLINDA/EXM software. Subsequently, pairs of dynamic brain scans were obtained for 11 healthy men to identify optimal methods for derivation of regional distribution volume and binding potential and to determine the repeatability of measurement. RESULTS: The whole-body effective radiation dose was approximately 17 µSv/MBq (62 mrem/mCi), with the gallbladder receiving the highest dose of 190 µSv/MBq. In brain studies, time-activity curves showed high accumulation in the insula/caudate nucleus, moderate uptake in the thalamus, and the lowest concentration in the cerebellum/pons. The plasma reference graphical analysis method appeared optimal for (18)F-FPEB; it showed acceptable test-retest variability of nondisplaceable binding potential (<10%) and identified the highest nondisplaceable binding potential values (from ∼0.5 in the globus pallidus to ∼3.5 in the insula) for target regions. Safety assessments revealed no clinically meaningful changes in vital signs, electrocardiogram, or laboratory values. CONCLUSION: (18)F-FPEB is safe and well tolerated, and its regional cerebral distribution is consistent with previous reports in the literature for metabotropic glutamate receptors. The repeatability of measurement suggests that (18)F-FPEB is suitable for quantifying mGluR5 in humans.

Early acute hematogenous osteomyelitis detected by bone scintigraphy but not MRI.

Early diagnosis of acute hematogenous osteomyelitis (AHO) is crucial for effective management and to reduce the potential risk of lifelong deformities in pediatric patients. Both bone scintigraphy and MRI as current diagnostic imaging claim their high sensitivity in early detection of the disease. We present a 9-year-old girl patient with AHO in the distal right tibia, which was demonstrated on bone scintigraphy while a subsequent MRI on the same day was negative.