Intravenous access is difficult in some patients referred for ¹⁸F-FDG PET imaging. Extravasation at the injection site and accumulation in central catheters can lead to limited tumor ¹⁸F-FDG uptake, erroneous quantitation, and significant image artifacts. In this study, we compared the human biodistribution and dosimetry for ¹⁸F-FDG after oral and intravenous administrations sequentially in the same subjects to ascertain the dosimetry and potential suitability of orally administered ¹⁸F-FDG as an alternative to intravenous administration. We also compared our detailed intravenous ¹⁸F-FDG dosimetry with older dosimetry data. Methods: Nine healthy volunteers (6 male and 3 female; aged 19–32 y) underwent PET/CT imaging after oral and intravenous administration of ¹⁸F-FDG. Identical preparation and imaging protocols (except administration route) were used for oral and intravenous studies. During each imaging session, 9 whole-body PET scans were obtained at 5, 10, 20, 30, 40, 50, 60, 120, and 240 min after ¹⁸F-FDG administration (370 ± 16 MBq). Source organ contours drawn using CT were overlaid onto registered PET images to extract time–activity curves. Time-integrated activity coefficients derived from time–activity curves were given as input to OLINDA/EXM for dose calculations. Results: Blood uptake after orally administered ¹⁸F-FDG peaked at 45–50 min after ingestion. The oral-to-intravenous ratios of ¹⁸F-FDG uptake for major organs at 45 min were 1.07 ± 0.24 for blood, 0.94 ± 0.39 for heart wall, 0.47 ± 0.12 for brain, 1.25 ± 0.18 for liver, and 0.84 ± 0.24 for kidneys. The highest organ-absorbed doses (μGy/MBq) after oral ¹⁸F-FDG administration were observed for urinary bladder (75.9 ± 17.2), stomach (48.4 ± 14.3), and brain (29.4 ± 5.1), and the effective dose was significantly higher (20%) than after intravenous administration (P = 0.002). Conclusion: ¹⁸F-FDG has excellent bioavailability after oral administration, but peak organ activities occur later than after intravenous injection. These data suggest PET at 2 h after oral ¹⁸F-FDG administration should yield images that are comparable in biodistribution to conventional clinical images acquired 1 h after injection. Oral ¹⁸F-FDG is a palatable alternative to intravenous ¹⁸F-FDG when venous access is problematic.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging ¹⁸F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with ¹⁸F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of ^99mTc-sestamibi SPECT/CT, ^99mTc-sestamibi/pertechnetate subtraction imaging, and ^99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of ¹⁸F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: ¹⁸F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D₂ and D₃ receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (¹¹C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14–30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20–30 min; spleen as reference region) demonstrated a statistically significant reduction (–36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R² = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R² = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R² = 0.57, P = 0.05), nor did mean baseline proinsulin (R² = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D₃ receptor and dopamine D₂ receptor in HCs. No colocalization of the dopamine D₃ receptor or dopamine D₂ receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D₃ receptor, dopamine D₂ receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D₃ receptor and dopamine D₂ receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for ¹¹C-(+)-PHNO, a dopamine D₃ receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). ¹⁸F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-¹⁸F-fluoroethyl)-l-tyrosine (¹⁸F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-¹¹C-methyl)-l-methionine (¹¹C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for ¹⁸F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-¹⁸F-fluoro-l-phenylalanine (¹⁸F-FDOPA); and 100% and 70%–88%, respectively, for ¹¹C-choline. Conclusion: ¹⁸F-FET and ¹¹C-MET, both amino-acid tracers, showed a comparably higher sensitivity than ¹⁸F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, ¹⁸F-FET and ¹¹C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.

β-Cell antigen recognition by autoreactive T cells is essential in type 1 diabetes (T1D) pathogenesis. Recently, insulin hybrid peptides (HIPs) were identified as strong agonists for CD4 diabetogenic T cells. Here, using BDC2.5 transgenic and NOD mice, we investigated T-cell recognition of the HIP2.5 epitope, which is a fusion of insulin C-peptide and chromogranin A (ChgA) fragments, and compared it with the WE14 and ChgA_29–42 epitopes. We measured in situ two-dimensional affinity on individual live T cells from thymus, spleen, pancreatic lymph nodes, and islets before and after diabetes. Although preselection BDC2.5 thymocytes possess higher affinity than splenic BDC2.5 T cells for all three epitopes, peripheral splenic T cells maintained high affinity only to the HIP2.5 epitope. In polyclonal NOD mice, a high frequency (~40%) of HIP2.5-specific islet T cells were identified at both prediabetic and diabetic stages comprising two distinct high- and low-affinity populations that differed in affinity by 100-fold. This high frequency of high- and low-affinity HIP2.5 T cells in the islets potentially represents a major risk factor in diabetes pathogenesis.

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4⁺ T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4⁺ T cells, and improved regulation of CD4⁺ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.

A joint Chatham House-RUSI project that focuses on strengthening common understanding across the Atlantic and develop new ideas for how the US and Europe can better engage with and respond to China’s rise.

More on Transatlantic Dialogue on China

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

Immigrants from India are the second-largest foreign-born group in the United States, after Mexicans. Indian immigrants tend to be far more highly educated and have greater English proficiency than the foreign-born population overall. This Spotlight article offers the latest data on Indian immigrants, focusing on population size, state- and city-level distribution, occupation, educational attainment, and more.

Though small, the population of Canadians in the United States is quite diverse, and includes students, highly skilled professionals on H-1B or NAFTA visas, family migrants, and retirees. Canadian immigrants have much higher educational attainment and incomes than the native- and overall foreign-born populations. This article offers an interesting data snapshot of Canadians in the United States.

Large outflows of educated young people escaping high levels of unemployment, in tandem with inflows of unauthorized migrants, pose a fresh set of challenges for Greek policymakers. This Transatlantic Council on Migration report examines Greek emigration, and its economic implications, before exploring policy directions to minimize the costs and maximize the benefits of this mobility.

The Armenian diaspora, which significantly exceeds the country's resident population, has played an instrumental role in Armenia's political and economic development since independence in 1991. Yet a picture emerges of divergent currents within the diaspora, often seen from above as a unified entity. Delve into differences in engagement among Armenia's "old" and "new" diasporas with this feature article.

Authoritarian states have long attempted to restrict citizens’ movement. But what happens when their reach extends beyond their borders? The October 2018 assassination of Saudi journalist Jamal Khashoggi brought into sharp relief the long arm of these regimes in reaching citizens abroad. This phenomenon, “transnational authoritarianism,” further shows that the relationship between migration and authoritarianism is becoming more complex.

From being a source of labor emigration to the Gulf region to a destination for refugees from Syria, sub-Saharan Africa, and elsewhere, Egypt has long experienced different forms of mobility. This article, which profiles the trends and policies that have shaped Egypt's migration history, focuses on its long-standing use of migration as a soft-power tool to achieve its foreign policy aims and as a safety valve for political discontent.

This report discusses Spain’s changing migration patterns in the wake of dramatic economic downturn, paying special attention to the effects of the emigration of young, native-born Spaniards. The report also focuses on policies geared toward engaging the increasing number of Spaniards abroad, finding that much of Spain's policy towards diasporas predates the 1980s.

An MPI Leadership Visions discussion with the Foreign Minister of Mexico, Claudia Ruiz-Massieu, for her first public appearance in Washington, DC. 

OBJECTIVE

To describe sociodemographic and clinical characteristics of youth and young adults with type 1 diabetes who endorsed suicidal ideations as part of routine depression screening and the results of their suicide risk assessments.

OBJECTIVE

To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.

OBJECTIVE

To improve outcomes of patients with adult type 2 diabetes by decreasing HbA_1c undertesting, reducing the proportion of patients with poor glycemic control, and lowering mean HbA_1c levels using a quality improvement (QI) program.

OBJECTIVE

To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.

OBJECTIVE

To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

OBJECTIVE

Neonatal diabetes has been shown to be associated with high neuropsychiatric morbidity in a genotype-phenotype–dependent manner. However, the specific impact of different mutations on intellectual functioning is still insufficiently characterized. Specifically, only a small number of subjects with developmental delay have been comprehensively assessed, creating a knowledge gap about patients carrying the heaviest burden.

OBJECTIVE

Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association.

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

Joseph Tran
Oct 1, 2012; 30:173-178
Practical Pointers

Candace D. McNaughton
Apr 1, 2011; 29:51-59
Feature Articles

Elizabeth H. Harris
Jul 1, 2005; 23:115-119
Feature Articles

Melpomeni Peppa
Oct 1, 2003; 21:
Council's Voice

William H. Herman
Apr 1, 2001; 19:
Case Studies

Maya S. Indurkar
Jan 1, 2016; 34:54-57
Practical Pointers

Francine Ratner Kaufman
Oct 1, 2002; 20:
President's Pen

Martha M. Funnell
Jul 1, 2004; 22:123-127
Feature Articles

Karmeen D. Kulkarni
Oct 1, 2004; 22:190-192
Practical Pointers

Sara F. Morris
Dec 1, 2010; 28:12-18
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Joy Dugan
Oct 1, 2017; 35:232-238
Practical Pointers

Jason A. Winston
Oct 1, 2006; 24:160-166
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George D. Harris
Jul 1, 2007; 25:115-118
Case Studies

Vanessa J. Briscoe
Jul 1, 2006; 24:115-121
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Kerri L. Cavanaugh
Jul 1, 2007; 25:90-97
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Renza Scibilia
Jul 1, 2019; 37:302-303
Book Reviews

Andrew J.M. Boulton
Jan 1, 2005; 23:9-15
Feature Articles

Nehman Lauder
Oct 1, 2005; 23:191-192
Case Studies

Warren Clayton
Mar 1, 2009; 27:52-58
Features

Jana L. Wardian
Jul 1, 2018; 36:257-258
Commentary