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Graves' disease (GD), the most common cause of hyperthyroidism, is an autoimmune disease directly caused by circulating autoantibodies that bind and activate the TSH receptor, inducing metabolic activation of the thyroid gland; this may be associated with important cardiac (atrial fibrillation) and ocular (ophthalmopathy) complications. Treating GD with real curative intent implies the full elimination of the functioning thyroid parenchyma using surgery or radioactive iodine therapy (RAI). RAI has been used in humans with hyperthyroidism since 1941, thanks to the pioneering work of a physician (Dr. Saul Hertz) and a physicist (Dr. Arthur Roberts). The rationale of RAI is based on the effect of radiation of 131I on target cells leading to DNA damage, both directly, through breakage of molecular bonds, and indirectly through the formation of free radicals. In particular, irradiation causes a broad spectrum of cellular damage due to the production of reactive oxygen species and lipid peroxidation of the plasma membrane. Thus, RAI-related cellular death takes place through both apoptosis and necrosis. The aim of this review was to summarize indications, efficacy, safety profile, and dosimetric aspects of RAI treatment in patients affected by GD.

Retrospective study of a prospectively collected database at one center.Assess the outcomes and complications of adult spinal deformity (ASD) surgery in patients that are 75 years and older compared with patients of 65-75 years of age. With increasing amounts of ASD surgery being performed on elderly patients, it is important to assess how age plays a factor in corrective reconstruction surgery.Inclusion criteria for the study were all patients ≥ 65 years of age that underwent thoracolumbar deformity correction involving ≥ four levels at a single institution by two surgeons. Patients were divided based on age into 65-74.9 or ≥ 75 groups. Radiographic parameters were measured preoperatively, postoperatively, and at 2 years. The Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were collected preoperatively, at 1 year, and 2 years. Comorbidities included were based around the Charlson Comorbidity Index (CCI) and compared to the incidence of complications and need for further surgery.Both age groups had improvements in their radiographic parameters postoperatively which was maintained at 2 years. Comparing the different age groups with similar comorbidity burden in regard to complications and need for additional surgery yielded no statistically significant difference between groups. Both groups had comparable decreases in NRS and increases in ODI at 2 years.Analysis of our study population indicates that there is no difference between the outcomes and complications of deformity surgery in patients 75 years and older when compared to a younger elderly population. It also does not appear that a ≥ 3 comorbidity burden has a significant impact on the complications or need for additional surgery in our elderly spinal deformity surgery population.Level IV.

BACKGROUND Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the biodistribution data reported in healthy rats. The results were compared with the absorbed dose data of technetium-99m-mercaptoacetyltriglycine (99mTc- MAG3) as documented in the International Commission on Radiological Protection (ICRP) publication 80. METHODS The medical internal radiation dose (MIRD) formula was applied to extrapolate data from rats to human and to project the absorbed radiation dose for various organs in humans. S factor was calculated by Monte-Carlo N-particle (MCNP) simulation. RESULTS Our dose prediction shows that an injection of 18F-PFH or 124I-OIH in humans would result in an estimated effective absorbed dose of 0.09 or 0.17 µSv/MBq respectively for whole body, which is about 135 or 73 times respectively lower than that obtained with an injection of 99mTc-MAG3. All organs except kidneys would receive an estimated effective absorbed dose of

In our country, the sliding Flexible Intramedullary Nailing is used alone or in combination with Ilizarov frame in children with osteogenesis imperfecta. The study assesses the results of sliding intramedullary nailing in deformity correction in severe types of osteogenesis imperfecta. We retrospectively reviewed 17 consecutive cases (mean age 5.2 y.o.) of types III, IV and VII of osteogenesis imperfecta. In group I (9 patients) the transphyseal FIN was performed using titanium nails. Sliding flexible intramedullary nailing was associated with Ilizarov frame in group II in 8 children. Patients in group I had overall complication rate of 88.9%: proximal nail migration (3), early secondary torsional displacement (4), non-telescoping (12), angular deformity (2), delayed or non-union (2). The reoperation rate was 100%. In group II we observed complications in 6 patients: nail migration (2), bowing of femur (2), non-telescoping (3). The reoperation rate was 87.5%. Flexible intramedullary nailing allows realignment and good functional outcomes. Its major disadvantage is an important complication rate and related reoperation rate. The use of Ilizarov frame provides additional stability and allows early weight-bearing.

INTRODUCTION: Radiolabeled, low-molecular-weight prostate-specific membrane antigen (PSMA) inhibitors based on the Glu-ureido pharmacophore show promise for the detection and treatment of castration-resistant prostate cancer; however, high renal retention of activity, related in part to overexpression of PSMA in kidneys can be problematic. The goal of the current study was to investigate the use of brush border enzyme-cleavable linkers as a strategy for reducing kidney activity levels from radiolabeled PSMA inhibitors. METHODS: PSMA-769 (6), a derivative of the prototypical PSMA inhibitor (((S)-1-carboxy-5-(4-iodobenzamido)pentyl)carbamoyl)glutamate (12) modified to contain a Gly-Tyr linker, and its protected tin precursor (11) were synthesized starting from the basic pharmacophore molecule Lys-urea-Glu. A radioiodinated analogue of 11 containing d-tyrosine in lieu of l-tyrosine (PSMA-769-d-tyrosine) also was synthesized from its corresponding tin precursor (d-11). Both radioiodinated and (211)At-labeled 6 were synthesized by radiohalogenation of 11 and deprotection in situ. Similarly, radioiodinated d-6 was synthesized from d-11. Paired label biodistribution of [(125)I]12 and [(131)I]6 was performed in normal mice and in SCID mice bearing both PC3 PIP (PSMA+) and PC3 flu (PSMA-) subcutaneous prostate carcinoma xenografts. The biodistribution of [(131)I]6 and [(211)At]6 was also evaluated in this tumor model. Biodistribution of the two radioiodinated diastereomers of 6 was evaluated in normal mice and urine samples were analyzed for the presence of 4-iodohippuric acid. RESULTS: Compounds [(131)I]6 and [(211)At]6 were synthesized from 11 in overall radiochemical yields of 32.5 ± 0.1% (n = 4) and 22% (n = 1), respectively; radiochemical purity was >95%. In normal mice, renal uptake of [(131)I]6 was 1.4-, 2.8- and 161-fold lower than that seen for co-injected [(125)I]12 at 1 h, 4 h and 21 h, respectively. In tumor-bearing mice, kidney uptake of [(131)I]6 was similar to that for [(125)I]12 (P > 0.05) at 1 h and 4 h but was 6- to 7-fold lower at 21 h; however, [(131)I]6 uptake in PC3 PIP tumors was also lower than that seen for [(125)I]12 at 21 h (12.6 ± 3.4 %ID/g vs. 36.8 ± 12.4 %ID/g). Uptake of [(211)At]PSMA-769 in PC3 PIP tumors was slightly higher than that seen for [(131)I]PSMA-769 at 4 h (9.6 ± 1.6 %ID/g versus 7.8 ± 1.6 %ID/g; P = 0.002); its uptake in a number of normal tissues also was higher. In normal mice, kidney uptake of [(125)I]PSMA-769 at 4 h was about 73% of that seen for [(131)I]PSMA-769- d-tyrosine. Activity in the urine of mice receiving [(125)I]PSMA-769 contained mainly 4-[(125)I]iodohippuric acid while unmetabolized intact molecule was present in the case of [(125)I]PSMA-769- d-tyrosine. CONCLUSION: Use of this brush border enzyme-cleavable linker reduced kidney uptake and resulted in improved tumor:kidney uptake ratios. Although further structural improvements are needed, this linker approach might be useful as a component in strategies for reducing renal uptake of radiolabeled PSMA inhibitors.

Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the biodistribution data reported in healthy rats. The results were compared with the absorbed dose data of technetium-99m-mercaptoacetyltriglycine (99mTc- MAG3) as documented in the International Commission on Radiological Protection (ICRP) publication 80.The medical internal radiation dose (MIRD) formula was applied to extrapolate data from rats to human and to project the absorbed radiation dose for various organs in humans. S factor was calculated by Monte-Carlo N-particle (MCNP) simulation.Our dose prediction shows that an injection of 18F-PFH or 124I-OIH in humans would result in an estimated effective absorbed dose of 0.09 or 0.17 µSv/MBq respectively for whole body, which is about 135 or 73 times respectively lower than that obtained with an injection of 99mTc-MAG3. All organs except kidneys would receive an estimated effective absorbed dose of0.1 µSv/MBq for 18F-PFH or 124I-OIH. Kidneys would receive a dose of 0.83 or 0.77 µSv/MBq respectively for 18F-PFH or 124I-OIH.Our results indicate that 18F-PFH and 124I-OIH would deliver much safer levels and lower radiation doses to the patients compared to 99mTc-MAG3 and warrants a clinical trial to estimate the radiation doses more accurately.

Background: ODM-201 is a novel second-generation androgen receptor inhibitor for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate the pharmacokinetics of ODM-201 tablet products and preliminary long-term safety, tolerability, and antitumor activity of ODM-201 in chemotherapy-naive men with mCRPC. Design, setting, and participants: Thirty patients were enrolled in this open-label phase 1 trial. Patients received a single 600-mg dose of ODM-201 in capsules with food and one 600-mg dose of ODM-201 tablet product (TabA or TabB) with food and in the fasted state in a random order. In the extension, patients received 600 mg twice daily ODM-201 taken with food in capsules. Outcome measurements and statistical analysis: We analyzed the pharmacokinetics of ODM-201 tablet formulations. Safety and tolerability were assessed until disease progression or an intolerable adverse event (AE). Antitumor activity was assessed by prostate-specific antigen (PSA) levels and imaging. Results and limitations: The capsule: TabA ratio of area under the concentration-time curve from time zero to the last sample at 48 h was 1.06 (90% confidence interval [CI], 0.91-1.24); the capsule: TabB ratio was 0.97 (90% CI, 0.82-1.14). At week 12, 25 of 30 patients (83%) had a PSA response (>= 50% reduction from baseline). Median time to radiographic progression was 66 wk (95% CI, 41-79). Most common AEs were fatigue (n = 4 [13%]) and nausea (n = 4 [13%]). Conclusions: The study showed that the tablet formulation of ODM-201 had similar pharmacokinetics compared with the capsule. Treatment with a 600-mg twice daily dose of ODM-201 provided anticancer activity and was well tolerated in men with chemotherapy-naive mCRPC. Patient summary: The findings of this study showed that ODM-201 is well tolerated and provided antitumor activity in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) and that the 300-mg tablet formulation can be used in further clinical studies. A phase 3 trial with ODM-201 600 mg twice daily in patients with non-mCRPC is ongoing. (C) 2015 European Association of Urology. Published by Elsevier B.V.

Ortho-[(131)I]iodohippurate [(131)I]OIH (marketed as Hippuran I 131), a gold standard for radionuclide renography, and [(123)I]OIH were in clinical use for decades. Here we radiolabeled OIH with (124)I (a positron emitter) to combine the desirable biological properties of OIH and to enable the use of positron emission tomography (PET) for renography. [(124)I]OIH was synthesized with a slight modification to a previously reported method for the kit preparation of [(123)I]OIH based on the Cu(II) catalyzed isotope-exchange reaction. Our method utilized heating at 120°C under sealed condition in a heating block instead of autoclaving. [(124)I]OIH was obtained with a radiochemical purity of >99.3%, radiochemical yield of 94.5%, and specific activity of ~17 MBq/mg. Biodistribution studies in healthy Sprague Dawley rats revealed results comparable to that of [(131)I]OIH as reported in the literature. The PET-derived [(124)I]OIH renograms revealed an average time-to-peak of 2.8±0.4min and the average time-to-half-maximal activity of 11.4±1.5min, which are also comparable to that of [(131)I]OIH as reported in the literature. Results from this study indicate that the synthesis of [(124)I]OIH without using an autoclave and [(124)I]OIH PET renography are feasible.

Objectives Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. Methods First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. Results The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. Conclusions Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. Key points • Renal blood flow (RBF) can be accurately measured by phase-contrast MRI in ADPKD patients. • RBF measured by phase-contrast is associated with ADPKD disease severity. • RBF measurement by phase-contrast MRI may be less feasible in patients with an impaired eGFR. Electronic supplementary material The online version of this article (doi:10.1007/s00330-015-3877-y) contains supplementary material, which is available to authorized users.

Introduction Little is known about the natural course of renal function and renal hemodynamics in heart failure patients with reduced ejection fraction (HFREF). Methods and results We prospectively studied effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in 73 HFREF patients with 125I-iothalamate/131I-hippuran clearances with a mean follow-up of 34.6 ± 4.4 months. Fifteen percent were female, with age 58 ± 12 years and left ventricular ejection fraction (LVEF) 29 ± 10 %. Baseline GFR was 81 ± 23 mL/min/1.73 m2 and declined 0.6 ± 4.7 mL/min/1.73 m2 per year. Baseline ERPF was 292 ± 83 mL/min/1.73 m2 and declined 4.3 ± 19 mL/min/1.73 m2 per year. Of the baseline variables, older age and high urinary kidney injury molecule-1 were the only variables associated with GFR decline (p