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Using a molecular modeling approach for Tau-binding sites, we modified our previously reported imaging agent, [125I]INFT, for the potential improvement of binding properties to Tau in an Alzheimer's disease (AD) brain. Two new derivatives, namely [125I]ISAS and [125I]NIPZ, were designed, where binding energies at site 1 of Tau were -7.4 and -6.0 kcal/mole, respectively, compared to [125I]INFT (-7.6 kcal/mole). The radiosynthesis of [125I]ISAS and [125I]NIPZ was carried out by using iodine-125 and purified chromatographically to achieve >90% purity. In vitro binding affinities (IC50) for Tau were as follows: INFT = 7.3 × 10-8 M; ISAS = 4.7 × 10-8 M; NIPZ > 10-6 M. The binding of [125I]ISAS to gray matter (GM) correlated with the presence of Tau in the AD brain, confirmed by anti-Tau immunohistochemistry. [125I]NIPZ did not bind to Tau, with similar levels of binding observed in GM and white matter (WM). Four radiotracers were compared and the rank order of binding to Tau was found to be [125I]IPPI > [125I]INFT > [125I]ISAS >>> [125I]NIPZ with GM/WM ratios of [125I]IPPI = 7.74 > [125I]INFT = 4.86 > [125I]ISAS = 3.62 >> [125I]NIPZ = 1.24. The predictive value of Chimera-AutoDock for structurally related compounds binding to the Tau binding sites (measured as binding energy) was good. A binding energy of less than -7 kcal/mole is necessary and less than -8 kcal/mole will be more suitable for developing imaging agents.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine & epsilon;-nitrogen atom, a dipeptide including two phenylalanine residues in the L-configuration as the peptide fragment of the linker, and 3- or 4-(tributylstannyl)benzoic acid as a prosthetic group in their structures for radiolabeling. The standard compounds [I-127]PSMA-m-IB and [I-127]PSMA-p-IB for comparative and characterization studies were first synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach, in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence followed by replacement of the Sn(Bu)(3) group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [I-123]PSMA-p-IB was higher than that of [I-123]PSMA-m-IB, which were 74.9 & PLUSMN; 1.0% and 49.4 & PLUSMN; 1.2%, respectively. The radiochemical purity of [I-123]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [I-123]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [I-123]PSMA-p-IB showed less accumulation than [Lu-177]Lu-PSMA-617 in several normal organs (liver, kidney, and bone). These results warrant further preclinical development, including toxicology evaluation and experiments in tumor-bearing mice.

BACKGROUND: Single photon emission computed tomography (SPECT) is an imaging modality that has demonstrated its utility in a number of clinical indications. Despite this progress, a high sensitivity, high spatial resolution, multi-tracer SPECT with a large field of view suitable for whole-body imaging of a broad range of radiotracers for theranostics is not available. PURPOSE: With the goal of filling this technological gap, we have designed a cadmium zinc telluride (CZT) full-ring SPECT scanner instrumented with a broad-energy tungsten collimator. The final purpose is to provide a multi-tracer solution for brain and whole-body imaging. Our static SPECT does not rely on the dual- and the triple-head rotational SPECT standard paradigm, enabling a larger effective area in each scan to increase the sensitivity. We provide a demonstration of the performance of our design using a realistic model of our detector with simulated body-sized phantoms filled with 99m Tc and 177 Lu. METHODS: We create a realistic model of our detector by using a combination of a Geant4 Application for Tomographic Emission (GATE) Monte Carlo simulation and a finite element model for the CZT response, accounting for low-energy tail effects in CZT that affects the sensitivity and the scatter correction. We implement a modified dual-energy-window scatter correction adapted for CZT. Other corrections for attenuation, detector and collimator response, and detector gaps and edges are also included. The images are reconstructed using the maximum-likelihood expectation-maximization. Detector and reconstruction performance are characterized with point sources, Derenzo phantoms, and a body-sized National Electrical Manufacturers Association (NEMA) Image Quality (IQ) phantom for both 99m Tc and 177 Lu. RESULTS: Our SPECT design can resolve 7.9 mm rods for 99m Tc (140 keV) and 9.5 mm for 177 Lu (208 keV) in a hot-rod Derenzo phantom with a 3-min exposure and reach an image contrast of 78

Background: The utility of serum thyroglobulin (Tg) measurement following partial thyroidectomy or total/near-total thyroidectomy without radioactive iodine (RAI) for differentiated thyroid cancer is unclear. This systematic review examines the diagnostic accuracy of serum Tg measurement for persistent, recurrent, and/or metastatic cancer in these situations. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched in October 2021 for studies on Tg measurement following partial thyroidectomy or total/near-total thyroidectomy without or before RAI. Quality assessment was performed, and evidence was synthesized qualitatively. Results: Thirty-seven studies met inclusion criteria. Four studies (N = 561) evaluated serum Tg measurement following partial thyroidectomy, five studies (N = 751) evaluated Tg measurement following total/near-total thyroidectomy without RAI, and 28 studies (N = 7618) evaluated Tg measurement following total or near-total thyroidectomy before RAI administration. Following partial thyroidectomy, Tg measurement was not accurate for diagnosing recurrence or metastasis, or estimates were imprecise. Following total/near-total thyroidectomy without RAI, evidence was limited due to few studies with very low rates of recurrence or metastasis, but indicated that Tg levels were usually stable and low. For Tg measurements before RAI administration, diagnostic accuracy for metastatic disease or persistence varied, although sensitivity appeared high (but specificity low) at a cutoff of >1 to 2.5 ng/mL. However, applicability to patients who do not undergo RAI is uncertain because patients selected for RAI are likely to represent a higher risk group. The evidence was very low quality for all scenarios. All studies had methodological limitations, and there was variability in the Tg thresholds evaluated, patient populations, outcomes assessed, and other factors. Conclusions: Very limited evidence suggests low utility of Tg measurement for identifying

STUDY OBJECTIVES: The most sensitive and specific investigative method for the diagnosis of narcolepsy type 1 (NT1) is the determination of hypocretin-1 (orexin-A) deficiency (≤110 pg/mL) in cerebrospinal fluid using a radioimmunoassay (RIA). We aimed to assess the reliability of the Phoenix Pharmaceuticals hypocretin-1 RIA, by determining the lower limit of quantification (LLOQ), the variability around the cutoff of 110 pg/mL, and the inter- and intra-assay variability. METHODS: Raw data of 80 consecutive hypocretin-1 RIAs were used to estimate the intra- and inter-assay coefficient of variation (CV). The LLOQ was established and defined as the lowest converted concentration with a CV <25%; the conversion is performed using a harmonization sample which is internationally used to minimize variation between RIAs. RESULTS: The mean intra-assay CV was 4.7%, while the unconverted inter-assay CV was 28.3% (18.5% excluding 2 outliers) and 7.5% when converted to international values. The LLOQ was determined as 27.9 pg/mL. The intra-assay CV of RIAs with lower specific radioactive activity showed a median of 5.6% (n = 41, range 1.6%-17.0%), which was significantly higher than in RIAs with higher specific activity (n = 36; median 3.2%, range 0.4%-11.6%, p = .013). The CV around the 110 pg/mL cutoff was <7%. CONCLUSIONS: Hypocretin-1 RIAs should always be harmonized using standard reference material. The specific activity of an RIA has a significant impact on its reliability, because of the decay of 125I radioactivity. Values around the hypocretin-1 cut-off can reliably be measured. Hypocretin-1 concentrations below 28 pg/mL should be reported as "undetectable" when measured with the Phoenix Pharmaceuticals RIA. CLINICAL TRIAL INFORMATION: This study is not registered in a clinical trial register, as it has a retrospective database design.

BackgroundWhile there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume.MethodsTo assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined.ResultsThe analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P < 0.001). Heterogeneity of association was observed by attained age (P < 0.001) with statistically significant association remaining only in the subgroup of ≥18 years at screening (P < 0.001). For this group, increase in dose from 0.0005 to 0.15 Gy was associated with a 1.27 ml (95% CI: 0.46, 2.07) increase in thyroid volume. The estimated effect did not change with increasing doses above 0.15 Gy.ConclusionsThis is the first study to examine the association between 131I dose to the thyroid gland and thyroid volume in a population of individuals exposed during childhood and systematically screened 10-15 years later. It provides evidence for a moderate statistically significant increase in thyroid volume among those who were ≥ 18 years at screening. Given t

type:Text, It has been challenging to obtain reliable estimates of thyroid equivalent doses (TEDs) to residents involved in the 11 March 2011 Fukushima Daiichi Nuclear Power Plant (FDNPP) accident because of the shortage of direct human measurements associated with 131I, the largest contributor to the dose of concern. The present study attempted to perform the estimation of the TEDs by inhalation of 131I to residents from Namie-town, one of the most radiologically-affected municipalities, by means of the latest atmospheric transport and dispersion model (ATDM) simulations with the Worldwide version of System for Prediction of Environmental Emergency Dose Information (WSPEEDI) ver. 2, coupled with personal behavioral data containing the history of the whereabouts of individuals shortly after the accident. We analyzed 1,637 residents who underwent direct measurements with whole-body counters several months after the accident and provided their personal behavioral data. We divided the subjects into two groups based on whether the distances between their locations and the FDNPP were >20 km as of 15:00 on 12 March in relation to the timepoint of the hydrogen explosion at the Unit 1 Reactor building. As a result, the 90th percentile TEDs of the 1,249 prompt evacuees and 388 late evacuees were 3.9 mSv (adult)-6.8 mSv (10-y-old) and 24.1 mSv (adult)-35.6 mSv (5-y-old), respectively, excluding 16 persons whose TEDs exceeded 50 mSv. The 90th percentile (median) TEDs to 1-y-old children (not included in the subjects) for the prompt and late evacuation groups were 8.1 (1.0) mSv and 36.3 (19.7) mSv, respectively. Additionally, this study provided the evidence to support the view that the explosive event at the Unit 1 Reactor building on the afternoon of 12 March 2011 could have caused the critical group among Namie-town's residents, whereas the largest release event on 15 March gave relatively small doses to the residents because their exposure took place mostly at sites that were distant

Background: In response to evidence of overdiagnosis and overtreatment of papillary thyroid carcinoma (PTC), the 2009 and 2015 American Thyroid Association (ATA) adult guidelines recommended less extensive surgery (lobectomy vs. total thyroidectomy) and more restricted use of postsurgical radioactive iodine (RAI) in management of PTC at low risk of recurrence. In 2015, active surveillance was suggested as a viable option for some <1-cm PTCs, or microcarcinomas. The 2015 ATA pediatric guidelines similarly shifted toward more restricted use of RAI for low-risk PTCs. The impact of these recommendations on low-risk adult and pediatric PTC management remains unclear, particularly after 2015. Methods: Using data from 18 Surveillance, Epidemiology, and End Results (SEER) U.S. registries (2000-2018), we described time trends in reported first-course treatment (total thyroidectomy alone, total thyroidectomy+RAI, lobectomy, no surgery, and other/unknown) for 105,483 patients diagnosed with first primary localized PTC (without nodal/distant metastases), overall and by demographic and tumor characteristics. Results: The declining use of RAI represented the most pronounced change in management of PTCs <4 cm (44-18% during the period 2006-2018), including microcarcinomas (26-6% during the period 2007-2018). In parallel, an increasing proportion of PTCs were managed with total thyroidectomy alone (35-54% during the period 2000-2018), while more subtle changes were observed for lobectomy (declining from 23% to 17% during the period 2000-2006, stabilizing, and then rising from 17% to 24% during the period 2015-2018). Use of nonsurgical management did not meaningfully change over time, impacting <1% of microcarcinomas annually during the period 2000-2018. Similar treatment trends were observed by sex, age, race/ethnicity, metropolitan vs. nonmetropolitan residence, and insurance status. For pediatric patients (<20 years), use of RAI peaked in 2009 (59%), then decreased ma

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many advanced cancers but are recognized to cause treatment-limiting immune-related adverse events (IrAE). ICI-associated thyroiditis is the most common endocrine IrAE and usually resolves to permanent hypothyroidism. Optimal thyroid hormone replacement in these patients remains unclear. We report the levothyroxine (LT4) dose needed to achieve stable euthyroid state in patients with hypothyroidism from ICI-associated thyroiditis, with comparison to patients with Hashimoto's thyroiditis (HT) and athyreotic state. Methods: We conducted a retrospective study of adults with ICI-associated hypothyroidism treated with LT4 at an academic medical center. Patient data were collected from the electronic medical record. Cases had ICI exposure followed first by hyperthyroidism and then subsequent hypothyroidism. Controls were HT (positive thyroid autoantibodies, requiring LT4) and athyreotic (total thyroidectomy or radioiodine ablation, requiring LT4) patients. Patients with central hypothyroidism, thyroid cancer, pregnancy, gastrointestinal stromal tumors, and use of L-triiodothyronine were excluded. Our primary outcome compared LT4 dose needed to achieve euthyroid state (thyrotropin 0.3-4.7 mIU/L over >6 consecutive weeks) for ICI-associated hypothyroidism, HT, and athyreotic patients, considering the impact of age and possible interfering medications by linear regression modeling. Secondary analysis considered the impact of endocrine specialty care on the time to euthyroid state. Results: One hundred three patients with ICI-associated thyroiditis were identified. Sixty-six of the 103 patients achieved euthyroid state; 2 with intrinsic thyroid gland function recovery and 64 on LT4. The mean LT4 dose achieving stable euthyroid state was 1.45 ± standard deviation (SD) 0.47 mcg/[kg·day] in ICI-associated hypothyroidism, 1.25 ± SD 0.49 mcg/[kg·day] in HT, and 1.54 ± SD 0.38 mcg/[kg·day] in athy

Introduction and Objective: The objective of this paper is to educate professionals who deal with the diagnosis and treatment of thyroid and parathyroid pathologies about the oral health problem related to treatment with radioiodine (I-131) and to provide a guide to oral care in these patients. Synthesis: The management of patients undergoing radioiodine treatment is encompassed within a multidisciplinary context in which the role of the dentist is especially important to prevent and treat the oral side effects of I-131 as part of the oncology team. Their role is essential in examining the patient before starting treatment with I-131, developing a treatment plan for their oral pathologies, informing the patient of the risks and oral side effects of I-131, teaching oral hygiene techniques for alleviate the results of these side effects and prescribing fluoride treatments and antibacterial rinses. Conclusions: The patient treated with radioiodine has a predisposition to the appearance of caries and periodontal disease. The patient should be evaluated before starting therapy, eliminating all possible sources of pain, infection and oral bleeding. Dental treatment of these patients should be avoided once therapy has begun, except for emergency treatment. The dentist is a fundamental pillar as part of the treatment team for patients with thyroid cancer who are undergoing radioiodine therapy., Introducción y objetivo: El objetivo del presente trabajo es concienciar a los profesionales que se ocupan del diagnóstico y tratamiento de las patologías de tiroides y paratiroides sobre la problemática de la salud bucodental relacionada con el tratamiento con yodo 131 (I-131) y proporcionar una guía de cuidados bucodentales en estos pacientes. Síntesis: El manejo del paciente en tratamiento con radioyodo se engloba dentro de un contexto multidisciplinar, en el que el rol del dentista es especialmente importante para prevenir y tratar los efectos secundarios orales del I-131, y por lo tanto debe formar parte de él. Su papel es fundamental en el examen del paciente antes de iniciar el tratamiento con I-131, elaborando un plan de tratamiento para sus patologías orales, informando al paciente de los riesgos y efectos secundarios orales del I-131, enseñando técnicas de higiene oral para paliar los resultados de dichos efectos secundarios y prescribiendo tratamientos con flúor y enjuagues antibacterianos. Conclusiones: El paciente en tratamiento con radioyodo tiene predisposición a la aparición de caries y enfermedad periodontal. Se debe evaluar al paciente antes de iniciar la terapia, eliminando todas las posibles fuentes de dolor, infección y hemorragia oral. Se debe evitar el tratamiento dental de estos pacientes una vez comenzada la terapia, salvo tratamientos de urgencia. El odontólogo es un pilar fundamental como parte del equipo multidisciplinar responsable del tratamiento del paciente con cáncer de tiroides sometido a terapia con radioyodo

[123I]FP-CIT SPECT has been valuable for distinguishing Parkinson disease (PD) from essential tremor. However, its performance for quantitative assessment of motor dysfunction has not been established. A virtual reality (VR) application was developed and compared with [123I]FP-CIT SPECT/CT for detection of severity of motor dysfunction. Forty-four patients (21 males, 23 females, age 64.5 ± 12.4) with abnormal [123I]FP-CIT SPECT/CT underwent assessment of bradykinesia, activities of daily living, and tremor with VR. Support vector machines (SVM) machine learning models were applied to VR and SPECT data. Receiver operating characteristic (ROC) analysis demonstrated greater area under the curve (AUC) for VR (0.8418, 95% CI 0.6071-0.9617) compared with brain SPECT (0.5357, 95% CI 0.3373-0.7357, p = 0.029) for detection of motor dysfunction. Logistic regression identified VR as an independent predictor of motor dysfunction (Odds Ratio 326.4, SE 2.17, p = 0.008). SVM for prediction of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) demonstrated greater R-squared of 0.713 (p = 0.008) for VR, compared with 0.0764 (p = 0.361) for brain SPECT. This study demonstrates that VR can be safely used in patients prior to [123I]FP-CIT SPECT imaging and may improve prediction of motor dysfunction. This test has the potential to provide a simple, objective, quantitative analysis of motor symptoms in PD patients.

Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection. A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to >35%, any improvement in LVEF of >10%, QRS shortening to <150 ms, or improvement in NYHA class of >1 class. In 33 patients LVEF increased to >35%, QRS decreased <150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to >35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by >10%. No independent predictors were found for QRS shortening to <150 ms or improvement in NYHA class. Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT.

Bakgrund: Graves sjukdom är den vanligaste formen av hypertyreos med en incidens på 20 fall per 100 000 individer och år. Graves sjukdom är ett autoimmunt tillstånd där autoantikroppar riktade mot tyreoideastimulerande hormonreceptorer (TSH-R) orsakar okontrollerad syntes och sekretion av tyreoideahormonerna trijodtyronin (T3) och tyroxin (T4). Hur tillståndet uppkommer är inte fullständigt förstått, riskfaktorer inkluderar dock rökning, kvinnligt kön och emotionell stress. Det finns i dagsläget tre etablerade behandlingsmetoder vid Graves sjukdom, dessa är tyreostatikabehandling, radiojodbehandling och tyreoidektomi. Behandling med tyreostatika pågår i regel i 12-18 månader, efter avslutad behandling är risken för recidiv mellan 50-60%. Både tyreoidektomi och radiojodbehandling är definitiva behandlingsmetoder som för majoriteten innebär övergång i hypotyreos med livslångt behov av levotyroxin-(LT4)behandling. Syfte: Syftet med examensarbetet var att undersöka långvarig effekt av radiojodbehandling vid Graves sjukdom och hur radiojodbehandling påverkar livskvalitet. Metod: Arbetet utfördes som en litteraturstudie, en sökning efter kliniska studier gjordes i PubMed med sökorden ”Graves disease” AND ”iodine radioisotopes”. Totalt åtta artiklar som i praktiken baserades på fem studier inkluderades i litteraturstudien. Resultat: Studie 1A, 1B och 1C var uppföljningsstudier av en tidigare utförd randomiserad klinisk studie. I studie 1A sågs det att samtliga individer som behandlats för Graves sjukdom hade sämre livskvalitet än den generella befolkningen 14-21 år efter behandling, ingen skillnad kunde ses beroende på behandlingsmetod. Studie 1B visade att skillnaderna i livskvalitet som funnits i studie 1A inte berodde på tyreoideahormonstatus. Resultaten i studie 1C visade att autoimmun aktivitet i form av tyreoideastimulerande hormonreceptorantikropp(TRAk)-nivåer var förhöjda bland individer som behandlats med radiojod i samtliga fem år som uppföljningen skedde, bland, Graves´ disease is an autoimmune disease resulting in uncontrolled auto antibody-mediated secretion of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Graves´ disease is the most common cause of hyperthyroidism and has an annual incidence of 20 cases per 100 000 inhabitants. The pathogenesis of the disease is not yet fully understood, but risk factors include smoking, female gender and emotional stress. Since thyroid hormones act in almost every cell in the body, an imbalance in thyroid hormone levels can lead to severe consequences and affected quality of life. Symptoms of Graves´ disease include weight loss, tremor, tachycardia, heat intolerance, increased sweating, anxiety, fatigue and loss of libido. There are three established treatment approaches for Graves´ disease including antithyroid drugs, radioiodine treatment and surgical thyroidectomy. The treatment goal for Graves´ disease is to stop the hyperthyroid state and reduce the risk of complications from the condition. Antithyroid drugs is the treatment modality most frequently used in newly diagnosed Graves´ disease and the duration of treatment is normally 12-18 months. The risk of recurrence after antithyroid drugs is 50-60%. Both radioiodine treatment and surgery are considered definitive treatments for Graves´ disease, the majority of treated individuals become hypothyroid with a life-long need for levothyroxine (LT4) treatment. The three available treatment options have both advantages and disadvantages that should be discussed with the patient in each individual case. The aim of this study was to evaluate the long-term effects of radioiodine treatment for Graves´ disease and how radioiodine treatment affects the quality of life. This is a literature study based on eight articles that, in practice, were based on five different clinical trials. The included studies were collected from the database PubMed. Since the included studies were different in both study design and outcome, no ge

The metaiodobenzylguanidine (MIBG) scan is one of the most sensitive noninvasive lesion detection modalities for neuroblastoma. Unlike 123I-MIBG, 124I-MIBG allows high-resolution PET. We evaluated 124I-MIBG PET/CT for its diagnostic performance as directly compared with paired 123I-MIBG scans. Methods: Before 131I-MIBG therapy, standard 123I-MIBG imaging (5.2 MBq/kg) was performed on 7 patients, including whole-body (anterior-posterior) planar imaging, focused-field-of-view SPECT/CT, and whole-body 124I-MIBG PET/CT (1.05 MBq/kg). After therapy, 2 of 7 patients also completed 124I-MIBG PET/CT as well as paired 123I-MIBG planar imaging and SPECT/CT. One patient underwent 124I-MIBG PET/CT only after therapy. We evaluated all 8 patients who showed at least 1 123I-MIBG-positive lesion with a total of 10 scans. In 8 pairs, 123I-MIBG and 124I-MIBG were performed within 1 mo of each other. The locations of identified lesions, the number of total lesions, and the curie scores were recorded for the 123I-MIBG and 124I-MIBG scans. Finally, for 5 patients who completed at least 3 PET/CT scans after administration of 124I-MIBG, we estimated the effective dose of 124I-MIBG. Results: 123I-MIBG whole-body planar scans, focused-field-of-view SPECT/CT scans, and whole-body 124I-MIBG PET scans found 25, 32, and 87 total lesions, respectively. There was a statistically significant difference in lesion detection for 124I-MIBG PET/CT versus 123I-MIBG planar imaging (P < 0.0001) and 123I-MIBG SPECT/CT (P < 0.0001). The curie scores were also higher for 124I-MIBG PET/CT than for 123I-MIBG planar imaging and SPECT/CT in 6 of 10 patients. 124I-MIBG PET/CT demonstrated better detection of lesions throughout the body, including the chest, spine, head and neck, and extremities. The effective dose estimated for patient-specific 124I-MIBG was approximately 10 times that of 123I-MIBG; however, given that we administered a very low activity of 124I-MIBG (1.05 MBq/kg), the effective dose was on

ObjectiveTo understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI).MethodsAn online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked "what if" scenarios on core topics, including AS, extent of surgery, and indications for RAI.ResultsSurvey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS.ConclusionPatient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

BackgroundPapillary thyroid cancer (PTC) is the fastest increasing cancer in the United States; incidence increases with age. It generally has a favorable prognosis but may behave more aggressively in older patients. This study aims to describe national treatment patterns for low-risk PTC in older adults.Materials and methodsThe Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients ≥66 y treated for clinical T1N0M0 PTC between 1996 and 2011. Multivariable logistic regression was used to identify factors associated with extent of surgery (total thyroidectomy versus lobectomy) and radioactive iodine (RAI) administration. Cox proportional hazards modeling was used to estimate the effect of treatment type on disease-specific survival (DSS).ResultsThree thousand two hundred and fourteen patients met inclusion criteria; 77.6% were women, median age was 72 y, and mean tumor size was 0.7 cm. 42.7% had preoperatively diagnosed PTC (versus incidental). 65.4% underwent total thyroidectomy, 29.0% lobectomy, and 5.6% lobectomy followed by completion thyroidectomy; 33.4% received postoperative RAI. Five- and 10-year DSS were 98.9% and 98.3%, respectively. After adjustment, larger tumor size (1.1-2 cm), multifocality, and a preoperative PTC diagnosis were associated with greater odds of undergoing more extensive surgery and receiving RAI (P < 0.0001). DSS was not associated with extent of surgery or RAI administration (P > 0.05).ConclusionsMost older adults with PTC underwent total thyroidectomy and a third received RAI; neither treatment improved DSS. In the growing elderly population, less extensive interventions for PTC may reduce morbidity and improve quality of life while preserving an excellent prognosis.

PurposeRadiation dose calculated on tumors for radiopharmaceutical therapy varies significantly from tumor to tumor and from patient to patient. Accurate estimation of radiation dose requires multiple time point measurements using radionuclide imaging modalities such as SPECT or PET. In this report, we show our technical development of reducing the number of scans needed for reasonable estimation of tumor and normal organ dose in our pretherapy imaging and dosimetry platform of 124 I-metaiodobenzylguanidine (MIBG) positron emission tomography/computed tomography (PET/CT) for 131 I-MIBG therapy of neuroblastoma.MethodsWe analyzed the simplest kinetic data, areas of two-time point data for five patients with neuroblastoma who underwent 3 or 4 times of 124 I-MIBG PET/CT scan prior to 131 I-MIBG therapy. The data for which we derived areas were percent of injected activity (%IA) and standardized uptake value of tumors. These areas were correlated with time-integrated activity coefficients (TIACs) from full data (3 or 4 time points). TIACs are direct correlates with radiation dose as long as the volume and the radionuclide are known.ResultsThe areas of %IAs between data obtained from all the two-time points with time points 1 and 2 (day 0 and day 1), time points 2 and 3 (day 1 and day 2), and time points 1 and 3 (day 0 and day 2) showed reasonable correlation (Pearson's correlation coefficient |r| > 0.5) with not only tumor and organ TIACs but also tumor and organ absorbed doses. The tumor and organ doses calculated using %IA areas of time point 1 and time point 2 were our best fits at about 20% individual percent difference compared to doses calculated using 3 or 4 time points.ConclusionsWe could achieve reasonable accuracy of estimating tumor doses for subsequent radiopharmaceutical therapy using only the two-time point imaging sessions. Images obtained from these time points (within the 48-h after administration of radiopharmaceutical) were also viewed as

Background: Radioiodine is the treatment of choice for hyperthyroidism in cats. The ideal method of dose determination of radioiodine remains controversial. Objective: To compare a method of radioiodine dose determination that utilized thyroid scintigraphy with a standard fixed dose for treatment of hyperthyroidism. Animals: Fifty-seven and 23 client-owned hyperthyroid cats in the variable and fixed dose groups, respectively. Methods: Cats with a percent dose uptake using 99mTc-pertechnetate uptake on thyroid scintigraphy <5%, 5%-10%, and >10% were to receive 3, 3.5, or 4.5 millicuries (mCi) of radioiodine, respectively, administered SC. Radioiodine dose was adjusted according to thyroid gland size as determined by the thyroid:salivary size ratio and categorized as <5:1, 5-10:1, and >10:1. If the thyroid size fell into a higher dosing category than the percent dose uptake, the dose was increased accordingly. Cats in the fixed dose group received 4.5 mCi. Six months after treatment, cats were determined to be euthyroid, hypothyroid, or hyperthyroid based on serum thyroxine and thyroid stimulating hormone concentrations. Results: No difference in outcome was found between the variable and fixed dose treatment groups. Euthyroidism, hypothyroidism, and persistent hyperthyroidism developed in 61, 30, and 9% of cats in the fixed dose group compared to 58, 26, and 16%, respectively, in the variable dose group. Conclusions: A variable dosing method of radioiodine based on percent dose uptake primarily and thyroid gland size secondarily did not improve outcome compared to a standard fixed dose method.

The aim of this study was to compare the outcomes between 1-mm and 5-mm section computed tomography (CT)-based postimplant dosimetry., A series of 21 consecutive patients underwent permanent prostate brachytherapy. The postimplant prostate volume was calculated using 1-mm and 5-mm section CT. One radiation oncologist contoured the prostate on CT images to obtain the reconstructed prostate volume (pVol), prostate V(100) (percent of the prostate volume receiving at least the full prescribed dose), and prostate D(90) (mean dose delivered to 90% of the prostate gland). The same radiation oncologist performed the contouring three times to evaluate intraobserver variation and subjectively scored the quality of the CT images., The mean +/-1 SD postimplant pVol was 20.17 +/- 6.66 cc by 1-mm section CT and 22.24 +/- 8.48 cc by 5-mm section CT; the difference in the mean values was 2.06 cc (P < 0.01). The mean postimplant prostate V(100) was 80.44% +/- 7.06% by 1-mm section CT and 77.33% +/- 10.22% by 5-mm section CT. The mean postimplant prostate D(90) was 83.28% +/- 10.81% by 1-mm section CT and 78.60% +/- 15.75% by 5-mm section CT. In the evaluation of image quality, 5-mm section CT was assigned significantly higher scores than 1-mm section CT. In regard to intraobserver variation, 5-mm section CT revealed less intraobserver variation than 1-mm section CT., Our current results suggested that the outcomes of postimplant dosimetry using 1-mm section CT did not improved the results over those obtained using 5-mm section CT in terms of the quality of the CT image or reproducibility., The aim of this study was to compare the outcomes between 1-mm and 5-mm section computed tomography (CT)-based postimplant dosimetry., A series of 21 consecutive patients underwent permanent prostate brachytherapy. The postimplant prostate volume was calculated using 1-mm and 5-mm section CT. One radiation oncologist contoured the prostate on CT images to obtain the reconstructed prostate volume (pVol), prostate V(100) (percent of the prostate volume receiving at least the full prescribed dose), and prostate D(90) (mean dose delivered to 90% of the prostate gland). The same radiation oncologist performed the contouring three times to evaluate intraobserver variation and subjectively scored the quality of the CT images., The mean +/-1 SD postimplant pVol was 20.17 +/- 6.66 cc by 1-mm section CT and 22.24 +/- 8.48 cc by 5-mm section CT; the difference in the mean values was 2.06 cc (P < 0.01). The mean postimplant prostate V(100) was 80.44% +/- 7.06% by 1-mm section CT and 77.33% +/- 10.22% by 5-mm section CT. The mean postimplant prostate D(90) was 83.28% +/- 10.81% by 1-mm section CT and 78.60% +/- 15.75% by 5-mm section CT. In the evaluation of image quality, 5-mm section CT was assigned significantly higher scores than 1-mm section CT. In regard to intraobserver variation, 5-mm section CT revealed less intraobserver variation than 1-mm section CT., Our current results suggested that the outcomes of postimplant dosimetry using 1-mm section CT did not improved the results over those obtained using 5-mm section CT in terms of the quality of the CT image or reproducibility., source:https://link.springer.com/article/10.1007%2Fs11604-006-0096-0

This paper proposes an analysis methodology based on the spectral windows technique aimed for environmental real-time gamma-ray spectra obtained with scintillation detectors. The method permits us to monitor activity concentrations of selected isotopes, such as anthropogenic radionuclides like 137Cs and 131I, by removing the Compton scattering plus other external contributions and resolving peak overlapping within any window. Activity concentrations are presented for 137Cs, 131I, 214Bi, and 214Pb when applying the method to a monitor using a LaBr3(Ce) detector. The method avoids false-positive and false-negative results of anthropogenic radionuclides in the presence of radiation from natural origins by obtaining activity concentrations that correspond to those obtained by a Gaussian fitting commercial software.

BackgroundThe recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low-risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation.MethodsWe performed a retrospective analysis including patients with American Thyroid Association low- and low-to-intermediate risk well-differentiated thyroid cancer 1-4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy.ResultsA total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy.ConclusionDespite the tightened regulations for radioactive iodine, about 20% of patients with apparently "low-risk" well-differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

BackgroundSerum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency.MethodsWe screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality.ResultsMean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values<0.001), and Tg increased with increasing thyroid volume, and serum thyrotropin (p-values for trend<0.001). We found no evidence of significant associations between iodine-131 thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt intake (PC=-7.90, 95% confidence interval: -12.08, -3.52), and over the range of urinary iodine concentration, the odds of having elevated serum Tg showed a U-shaped curve with elevated Tg at low and high urinary iodine concentrations.ConclusionSerum Tg may be a useful indicator of population iodine status and a non-specific biomarker of structural and functional thyroid abnormalities in epidemiological studies.

ContextAlthough radiation exposure is an important predictor of thyroid cancer on diagnosis of a thyroid nodule, the relationship between childhood radiation exposure and thyroid nodules has not been comprehensively evaluated.ObjectiveTo examine the association between internal I-131 thyroid dose and thyroid nodules in young adults exposed during childhood.Design, setting, and participantsIn this cross-sectional study, we screened residents of Belarus aged ≤18 years at the time of the Chernobyl nuclear accident for thyroid disease (median age, 21 years) with thyroid palpation, ultrasonography, blood/urine analysis, and medical follow-up when appropriate. Eligible participants (N = 11,421) had intact thyroid glands and doses based on direct individual thyroid activity measurements.Main outcome measuresExcess odds ratios per Gray (EOR/Gy, scaled at age 5 years at exposure) for any thyroid nodule and for nodules grouped by cytology/histology, diameter size, and singularity.ResultsRisk of any thyroid nodule increased significantly with I-131 dose and, for a given dose, with younger age at exposure. The EOR/Gy (95% confidence intervals) for neoplastic nodules (3.82; 0.87 to 15.52) was significantly higher than for nonneoplastic nodules (0.32; <0.03 to 0.70) and did not vary by size; whereas the EOR/Gy for nonneoplastic nodules did vary by size (P = 0.02) and was 1.55 (0.36 to 5.46) for nodules ≥10 mm and 0.02 (<-0.02 to 0.70) for nodules <10 mm. EORs/Gy for single and multiple nodules were comparable.ConclusionsChildhood exposure to internal I-131 is associated with increased risk of neoplastic thyroid nodules of any size and nonneoplastic nodules ≥10 mm.

Purpose: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.Experimental Design: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model. Pairwise comparison of obinutuzumab-based antibody fragments labeled with residualizing (89Zr) versus non-residualizing (124I) radionuclides by region of interest analysis of serial PET images was conducted both in the murine lymphoma model and in huCD20TM to assess antigen modulation in vivoResults:124I-GAcDb and 124I-GAcMb produced high-contrast immunoPET images of B-cell lymphoma and outperformed the respective rituximab-based tracers. ImmunoPET imaging of huCD20TM showed specific uptake in lymphoid tissues. The use of the radiometal 89Zr as alternative label for GAcDb and GAcMb yielded greater target-specific uptake and retention compared with 124I-labeled tracers. Pairwise comparison of 89Zr- and 124I-labeled GAcDb and GAcMb allowed assessment of in vivo internalization of CD20/antibody complexes and revealed that CD20 internalization differs between malignant and endogenous B cells.Conclusions: These obinutuzumab-based PET tracers have the ability to noninvasively and quantitatively monitor CD20-expression and have revealed insights into CD20 internalization upon antibody binding in vivo Because they are based on a humanized mAb they have the potential for direct clinical translation and could improve patient selection for targeted therapy, dosimetry prior to radioimmunotherapy, and prediction of response to therapy. Clin Cancer Res; 23(23); 7242-52. ©2017 AACR.

Objetive: The objective is to present a case with successful I-131 uptake in a patient with Hürthle cell carcinoma. Case presentation: A 60 years old female patient with diagnosed goiter, that was treated with thyroid hormone analogues that didn’t decreased the growth of the mass; due to that, it was biopsied. The report of the pathology reported a Hürthle cell neoplasm with indeterminate behavior, lately oncologic thyroidectomy and lymphadenectomy were performed, from which the pathology plates were revised showing a definitive diagnosis of Hurthle cell carcinoma. The case was reviewed in a medical board where I-131 therapy was suggested. In the postheraphy scan performed, there was evidence of I-131 uptake in the neck and in an adenopathy. Twelve months later, there was evidence of pulmonary relapse. Is an uncertainty to know if the patient in this case would have been able to benefit from an early ablative therapy with I-131 decreasing the risk of relapse after having documented tumor avidity for it. The Hürthle thyroid carcinoma is rare, and its natural history is still controversial because it’s challenging diagnosis, treatment and monitoring. Because there is no definitive agree about his integral approach despite it has been considered differentiated thyroid cancer even therapy with I-131 is still debated., Objetivo: O fim deste artigo é dar a conhecer a experiência do manejo multidisciplinar de um caso documentado de carcinoma de células de Hürthle no qual encontrou-se captação com I-131 e pelo tanto opção terapêutica com o mesmo. Presentación de caso: Trata-se de uma paciente na sexta década da vida, diagnosticada inicialmente com bócio difuso que foi tratada com terapia de substituição hormonal com análogos de tiroxina sem resposta satisfatória, pelo que se realizou biopsia tireóidea, cujo resultado reportou neoplasia de células de Hürthle de comportamento inespecífico. Realizou-se tireoidectomia oncológica e linfadenectomia. Realizou-se revisão de placas de patologia e chegou-se a um diagnóstico definitivo de carcinoma de Hürthle. Levouse o caso à junta multidisciplinar e decide-se terapia com I-131 mas este processo levou a que a terapia se realizara de forma tardia; ainda assim evidencia-se no rastreamento pós-tratamento captação em adenopatia cervical. Finalmente, apresentou recaída pulmonar 12 meses depois. Este tipo de tumor pe um desafio para os médicos tratantes pela incerteza na sua história natural, no seu tratamento e na utilidade do I-131, esta útlima é muito debatida devido à sua alta tendência à desdiferenciação e à baixa percentagem dos mesmos que apesentam captação do radiofármaco. É incerto se a paciente deste caso se tivesse conseguido beneficiar de uma terapia ablativa com I-131 mais temporã diminuindo o risco de recaída após ter-se documentado avidez tumoral pelo mesmo., Objetivo: el fin de este artículo es dar a conocer la experiencia del manejo multidisciplinario de un caso documentado de carcinoma de células de Hürthle en el que se encontró captación con I-131 y por lo tanto opción terapéutica con el mismo. Presentación de caso: se trata de una paciente en la sexta década de la vida, diagnosticada inicialmente con bocio difuso quien fue manejada con terapia de sustitución hormonal con análogos de tiroxina sin respuesta satisfactoria, por lo que se realizó biopsia tiroidea, cuyo resultado reportó neoplasia de células de Hürthle de comportamiento inespecífico. Se realizó tiroidectomía oncológica y linfadenectomía. Se realizó revisión de placas de patología y se llegó a un diagnóstico definitivo de carcinoma de Hürthle. Se llevó el caso a junta multidisciplinaria y se decide terapia con I-131 pero este proceso llevó a que la terapia se realizara de forma tardía; aun así se evidencia en el rastreo postratamiento, captación en adenopatía cervical. Finalmente, presentó recaída pulmonar 12 meses después. Este tipo de tumor es un desafío para los médicos tratantes por la incertidumbre en su historia natural, en su tratamiento y en la utilidad del I-131, esta última es muy debatida debido a su alta tendencia a la desdiferenciación y al bajo porcentaje de los mismos que presentan captación del radiofármaco. Es incierto si la paciente de este caso se hubiese podido beneficiar de una terapia ablativa con I-131 más temprana disminuyendo el riesgo de recaída luego de haberse documentado avidez tumoral por el mismo.

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg×4); 131I- (1mCi or 2×0.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-.

BackgroundIncomplete surgical resection with gross positive tumor margin increases the risk of recurrence in patients with well-differentiated thyroid cancer (WDTC); however, it is not clear whether a microscopic positive margin found only on final pathology has similar implications on patient outcomes.MethodsWe conducted a single-institution retrospective review of all patients undergoing total thyroidectomy for T1-T2 WDTC (January 2000-January 2010). Factors that may influence the risk of locoregional recurrence or distant metastasis were evaluated by univariate and multivariate analysis.ResultsOf 1000 consecutive patients undergoing surgical resection for WDTC, 684 T1-T2 cancers were included. Mean age was 46 years and 81 % were women. Of this total cohort, 78 (11 %) patients had microscopic positive margins. Radioactive iodine (RAI) was administered in 47/78 (60 %) patients with positive margins versus 312/606 (51 %) patients without positive margins. After a mean follow-up of 46 months, 53 (8 %) patients developed recurrent disease (1 local and 52 nodal). On multivariate analysis, nodal metastases (N1, odds ratio [OR] 7.7) and contralateral multifocality (OR 3.7) were independent risk factors for recurrent disease. A microscopic positive margin was not a risk factor for recurrence.ConclusionsA microscopic positive margin found only on final pathological analysis does not increase the risk of recurrence in T1-T2 WDTC. Clinicians should interpret such pathology findings accordingly when considering further surveillance and treatment decisions such as the use of RAI ablation.

BackgroundPerineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 ( 125 I) seed implantation.MethodsThe in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125 I seeds CLDR irradiation. The orthotopic models of PNI were established, and 125 I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after 125 I seed implantation.ResultsThe co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months.ConclusionsThe CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.

BackgroundAbout half of patients with papillary thyroid cancer have tumours with activating BRAF(V600E) mutations. Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial. We aimed to establish the activity of vemurafenib in patients with BRAF(V600E)-positive papillary thyroid cancer.MethodsWe did an open-label, non-randomised, phase 2 trial at ten academic centres and hospitals worldwide in patients aged 18 years or older with histologically confirmed recurrent or metastatic papillary thyroid cancer refractory to radioactive iodine and positive for the BRAF(V600E) mutation. Participants either had never received a multikinase inhibitor targeting VEGFR (cohort 1) or had been treated previously with a VEGFR multikinase inhibitor (cohort 2). Patients received vemurafenib 960 mg orally twice daily. The primary endpoint was investigator-assessed best overall response in cohort 1 (confirmed on two assessments 4 weeks or longer apart). Analyses were planned to have a minimum median follow-up of 15 months (data cutoff April 18, 2014) and were done in safety, intention-to-treat, and per-protocol populations. This trial is closed and is registered at ClinicalTrials.gov, number NCT01286753.FindingsBetween June 23, 2011, and Jan 15, 2013, 51 patients were enrolled to the study, 26 in cohort 1 and 25 in cohort 2. Median duration of follow-up was 18·8 months (IQR 14·2-26·0) in cohort 1 and 12·0 months (6·7-20·3) in cohort 2. Partial responses were recorded in ten of 26 patients in cohort 1 (best overall response 38·5%, 95% CI 20·2-59·4). Grade 3 or 4 adverse events were recorded in 17 (65%) of 26 patients in cohort 1 and 17 (68%) of 25 patients in cohort 2; the most common grade 3 and 4 adverse events were squamous cell carcinoma of the skin (seven [27%] in cohort 1, five [20%] in cohort 2), lymphopenia (two [8%] in each cohort), and increa

Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients <45 years. 64,980 patients met study criteria; 39,778 (61.2 %) were cN0 versus 25,202 (38.8 %) pN0. Patients with pN0 nodes were more likely to have negative surgical margins and multifocal disease (all p < 0.001). The mean negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p < 0.001) and for patients aged <45 years (0R 0.86, p = 0.001). Patients with <5 pN0 nodes did not differ in RAI use compared to cN0 controls. Unadjusted survival was improved for pN0 versus cN0 patients across all ages (p < 0.001), but not for patients <45 years (p = 0.11); adjusted survival for all ages did not differ (p = 0.13). Pathological confirmation of negative lymph nodes in patients with PTC appears to influence the decision to administer po

The majority of patients with nonpalpable breast lesions are eligible for breast conserving surgery guided by some kind of lesion localization. The current standard is wire-guided localization (WGL) even though it has several disadvantages, the most important one being the considerable proportion of patients with insufficient resection margin. These patients require a reoperation. New methods in the field of radioguided surgery (RGS) have been developed including radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL). Especially RSL is a very promising technique. Guided by ultrasound a small titanium seed containing typically 1-10 MBq of radioactive iodine-125 is placed in the centre of the nonpalpable breast lesion. During the operation the seed is located with a hand-held gamma probe. To date, only few cohort studies exist on the feasibility of RSL, and the method has only been tested in one randomized trial. The results are either equal to or superior to those obtained with WGL, with regards to achieving free margins and low reoperation rates. Additionally, the RSL technique is less unpleasant for the patient and more flexible regarding preoperative logistics. The seed can be placed a few days before surgery, in contrast to the wire used in WGL, which has to be placed within few hours of surgery. RSL has quickly become popular in surgical and radiological teams that have used the technique and will probably become an important tool for preoperative localization of nonpalpable breast lesions in the near future.

Background(131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.MethodsPatients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.ResultsThirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg(-1). Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.ConclusionsMIBG (666 MBq kg(-1)) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at <2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure.

BackgroundThere are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.MethodsThis study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13,243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.ResultsWe identified a borderline significant linear-quadratic association (P=0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P=0.020) or tumours with BRAF or RAS point mutations (P=0.008). Controlling for age, there were significant time trends in decreasing tumour size (P<0.001), the extent of lymphatic/vascular invasion (P=0.005), and overall invasiveness (P=0.026).ConclusionsWe determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.

BackgroundRecent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear.MethodsA cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression.ResultsIn total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (P < .01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P < .03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P < .0001).ConclusionsI-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness.

PurposeIodine-131-m-iodobenzylguanidine ([(131)I]mIBG)-targeted radionuclide therapy (TRT) is a standard treatment for recurrent or refractory neuroblastoma with response rates of 30-40 %. The aim of this study is to demonstrate patient-specific dosimetry using quantitative [(124)I]mIBG positron emission tomography/X-ray computed tomography (PET/CT) imaging with a GEometry ANd Tracking 4 (Geant4)-based Monte Carlo method for better treatment planning.ProceduresA Monte Carlo dosimetry method was developed using the Geant4 toolkit with voxelized anatomical geometry and source distribution as input. The presegmented hybrid computational human phantoms developed by the University of Florida and the National Cancer Institute (UF/NCI) were used as a surrogate to characterize the anatomy of a given patient. S values for I-131 were estimated by the phantoms coupled with Geant4 and compared with those estimated by OLINDA|EXM and MCNPX for the newborn model. To obtain patient-specific biodistribution of [(131)I]mIBG, a 10-year-old girl with relapsed neuroblastoma was imaged with [(124)I]mIBG PET/CT at four time points prior to the planned [(131)I]mIBG TRT. The organ- and tumor-absorbed doses of the clinical case were estimated with the Geant4 method using the modified UF/NCI 10-year-old phantom with tumors and the patient-specific residence time.ResultsFor the newborn model, the Geant4 S values were consistent with the MCNPX S values. The S value ratio of the Geant4 method to OLINDA|EXM ranged from 0.08 to 6.5 of all major organs. The [(131)I]mIBG residence time quantified from the pretherapy [(124)I]mIBG PET/CT imaging of the 10-year-old patient was mostly comparable to those previously reported. Organ-absorbed dose for the salivary glands was 98.0 Gy, heart wall 36.5 Gy, and liver 34.3 Gy, while tumor-absorbed dose ranged from 143.9 to 1,641.3 Gy in different sites.ConclusionsPatient-specific dosimetry for [(131)I]mIBG TRT was accomplished using pretherapy [(124)I]mIBG PET

BackgroundRadioactive iodine (RAI) ablation is frequently performed after initial surgery for well-differentiated thyroid cancer (WDTC). We examined the frequency and timing of childbirth as well as nononcologic complications after RAI ablation for WDTC on a population level.MethodsA retrospective cohort study of 25,333 patients (18,850 women) with WDTC was performed using the California Cancer Registry and California Office of Statewide Health Planning and Development database, 1999-2008. The primary outcomes were birthrate and median time to first live birth among women of childbearing age. Secondary outcomes were nononcologic diagnoses occurring outside the acute setting (>30 days) after ablation.ResultsRAI ablation did not affect birthrate among women in the full dataset. However, in subgroup analyses, birthrate among women age 35-39 was significantly decreased in those who received RAI versus those who did not (11.5 versus 16.3 births per 1000 woman-years, p<0.001). Median time to first live birth after diagnosis of WDTC was prolonged among women who received RAI compared to those who did not (34.5 versus 26.1 months; p<0.0001). When 5-year age groups were examined individually, delay to first live birth was observed in women age 20-39 (p<0.05). This remained significant after adjustment for tumor characteristics, socioeconomic status, and marital status. The only nononcologic, nonreproductive adverse effect associated with RAI ablation was an increased rate of nasolacrimal stenosis (RR 3.44, p<0.0001).ConclusionsRAI ablation is associated with delayed childbearing in women across most of the reproductive lifespan, and with decreased birthrate in the late reproductive years. The underlying mechanism likely involves physician recommendation to delay pregnancy, as well as a potential impact of RAI on both reproductive choice and reproductive health. Further investigation is merited.

Purpose(131)I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination.Experimental designPatients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m(2)) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design.ResultsTwenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m(2) vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m(2) vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m(2) vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14.ConclusionsVorinostat at 180 mg/m(2)/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing.

Background(131)I-metaiodobenzylguanidine ((131)I-MIBG) is a targeted radiopharmaceutical with significant activity in high-risk relapsed and chemotherapy-refractory neuroblastoma. Our primary aim was to determine if there are differences in response rates to (131)I-MIBG between patients with relapsed and treatment-refractory neuroblastoma.MethodsThis was a retrospective cohort analysis of 218 patients with refractory or relapsed neuroblastoma treated with (131)I-MIBG at UCSF between 1996 and 2014. Results were obtained by chart review and database abstraction. Baseline characteristics and response rates between relapsed patients and refractory patients were compared using Fisher exact and Wilcoxon rank sum tests, and differences in overall survival (OS) were compared using the log-rank test.ResultsThe response rate (complete and partial response) to (131)I-MIBG-based therapies for all patients was 27%. There was no difference in response rates between relapsed and refractory patients. However, after (131)I-MIBG, 24% of relapsed patients had progressive disease compared to only 9% of refractory patients, and 39% of relapsed patients had stable disease compared to 59% of refractory patients (p=0.02). Among all patients, the 24-month OS was 47.0% (95% confidence interval (CI) 39.9-53.9%). The 24-month OS for refractory patients was significantly higher at 65.3% (95% CI 51.8-75.9%), compared to 38.7% (95% CI 30.4-46.8%) for relapsed patients (p<0.001).ConclusionsAlthough there was no significant difference in overall response rates to (131)I-MIBG between patients with relapsed versusrefractory neuroblastoma, patients with prior relapse had higher rates of progressive disease and had lower 2-year overall survival after (131)I-MIBG compared to patients with refractory disease.

Background and objective Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity. Methods In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex, Charlson's comorbidity score, atrial fibrillation and previous cerebrovascular events. Results Mean follow-up time was 11.5 years, mean age 61 years, with a total number of 3228 events. Comparing all radioiodine-treated patients with controls, the fully adjusted model showed increased risk of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09–1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07–1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02–1.44). Conclusions We report an increased risk of cerebrovascular events in hyperthyroid as well as euthyroid patients treated with radioiodine for benign thyroid disorders. That these patient groups have similar risks suggests the possibility that radiation from radioiodine contributes to cerebrovascular morbidity via acceleration or initiation of atherosclerosis., BACKGROUND AND OBJECTIVE: Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity.METHODS: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex, Charlson's comorbidity score, atrial fibrillation and previous cerebrovascular events.RESULTS: Mean follow-up time was 11.5 years, mean age 61 years, with a total number of 3228 events. Comparing all radioiodine-treated patients with controls, the fully adjusted model showed increased risk of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09-1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07-1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02-1.44).CONCLUSIONS: We report an increased risk of cerebrovascular events in hyperthyroid as well as euthyroid patients treated with radioiodine for benign thyroid disorders. That these patient groups have similar risks suggests the possibility that radiation from radioiodine contributes to cerebrovascular morbidity via acceleration or initiation of atherosclerosis.

In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG-PET/CT plays in clinical practice is that it can be used to obtain prognostic information in patients with increasing thyroglobulin (Tg) levels and negative (131)I whole-body scan post-thyroidectomy and radioiodine (RAI) ablation. FDG-PET/CT may also have a potential role in the initial staging and follow-up of high-risk patients with aggressive histological subtypes, in the identification of patients who are at the highest risk of disease-specific mortality, in the management of patients with RAI-refractory disease, in clinical trials of novel targeted therapies in patients with advanced metastatic disease, and in the evaluation of thyroid nodules with indeterminate fine-needle aspiration for cytology. However, several controversies remain to be resolved, namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT, whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas. The aim of the present article is to provide an overview of the data about the molecular basis for, clinical indications of, and controversies related to the use of FDG-PET/CT in patients with DTC.

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy(-1) (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy(-1) (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy(-1) (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p = 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and cl

BACKGROUND: Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD.METHODS: In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by [(123)I]FP-CIT SPECT tracer binding to the dopamine transporter (DaT).RESULTS: Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients.CONCLUSIONS: These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.

PurposeThe PET tracer, (124)I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal (89)Zr, however, may offer advantages as a surrogate PET nuclide over (124)I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between (124)I-cG250 and (89)Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover.MethodsWe conducted experiments with (89)Zr-cG250 and (124)I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling.ResultsThe two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using (89)Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 × 10(12) molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of (124)I/(89)Zr atoms released per unit time by tumor was 17.5.ConclusionPairwise evaluation of (89)Zr-cG250 and (124)I-cG250 provided the

PurposeProstate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to (18)F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation.Experimental designOsteoblastic, PSCA-expressing, LAPC-9 intratibial xenografts were imaged with serial (124)I-anti-PSCA A11 minibody immunoPET and (18)F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and posttreatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation.ResultsA11 minibody demonstrated improved sensitivity and specificity over (18)F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo.ConclusionsA11 minibody immunoPET has the potential to improve the sensitivity and specificity of clinical prostate cancer metastasis detection over bone scans, which are the current clinical standard-of-care. A11 minibody immunoPET additionally has the potential to image the activity of the androgen signaling axis in vivo which may help evaluate the clinical response to androgen deprivation and the development of castration resistance.

PurposeSeveral new technologies for single photon emission computed tomography (SPECT) instrumentation with parallel-hole collimation have been proposed to improve detector sensitivity and signal collection efficiency. Benefits from improved signal efficiency include shorter acquisition times and lower dose requirements. In this paper, the authors show a possibility of over an order of magnitude enhancement in photon detection efficiency (from 7.6 × 10(-5) to 1.6 × 10(-3)) for dopamine transporter (DaT) imaging of the striatum over the conventional SPECT parallel-hole collimators by use of custom-designed 20 multipinhole (20-MPH) collimators with apertures of 0.75 cm diameter.MethodsQuantifying specific binding ratio (SBR) of (123)I-ioflupane or (123)I-iometopane's signal at the striatal region is a common brain imaging method to confirm the diagnosis of the Parkinson's disease. The authors performed imaging of a striatal phantom filled with aqueous solution of I-123 and compared camera recovery ratios of SBR acquired between low-energy high-resolution (LEHR) parallel-hole collimators and 20-MPH collimators.ResultsWith only two-thirds of total acquisition time (20 min against 30 min), a comparable camera recovery ratio of SBR was achieved using 20-MPH collimators in comparison to that from the LEHR collimator study.ConclusionsTheir systematic analyses showed that the 20-MPH collimator could be a promising alternative for the DaT SPECT imaging for brain over the traditional LEHR collimator, which could give both shorter scan time and improved diagnostic accuracy.

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.