Treatment Response following Radioactive Iodine Therapy in Miliary versus Macronodular Pulmonary Metastases in Papillary Thyroid Carcinoma.

Background Pulmonary metastases in papillary thyroid carcinoma have two common presentations-micro/miliary (MM) and macronodular metastases (MN). The mainstay of treatment, posttotal thyroidectomy, is multiple radioactive iodine ablations (RAIA) every 6 to 12 months. Response assessment is determined by decline in stimulated serum thyroglobulin levels (sTg), disease regression on chest x-ray (CXR), computed tomography thorax, or whole body iodine scintigraphy (TWBS). Aim This study aims to assess the difference in response to RAIA based on the pattern of presentation. Methodology Retrospective analysis of patients from January 2008 to July 2017 was done. Patients with pulmonary metastases treated with RAIA (3700MBq per therapy as opposed to theAmerican Thyroid Association recommendation of 7400MBq per therapy) and a minimum follow-up of 8 months were included. The initial and the final sTg, TWBS, and CXR were analyzed for both groups. Final outcome in terms of complete response, disease regression, static disease, and disease progression was determined. Results Of the total of 1,793 patients, 71 were included. There were 43 females and 28 males. The median age was 39 years and the range was 14 to 79 years. Forty-five (63.3%) patients had MM and 26 (36.6%) patients had MN disease. The average number of therapies was three and maximum follow-up period was 15 years. Of the 45 MM patients, 1 had progression, 7 were static, 23 had regression, and 14 had complete response. Of the 26 MN patients, 22 had progression, 2 were static, 1 had regression, and 1 had complete response. Conclusion MM metastases, when compared with MN disease, respond to RAIA with a better outcome. In addition to achieving comparable response with a lower dose per therapy, there were no radiation-related long-term complications reported.

ROC study and SUV threshold using quantitative multi-modal SPECT for bone imaging.

BACKGROUND: We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99mTc-methylene diphosphonate (MDP) or 99mTc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis. METHODS: Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a "surrogate truth" reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake. RESULTS: On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUVc) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUVc > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUVc > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUVc > 8.61 (xQ) or > 13.4 (xB). CONCLUSION: The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft-Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland-Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

T-cell receptor (TCR)-peptide specificity overrides affinity-enhancing TCR-major histocompatibility complex interactions.

αß T-cell receptors (TCRs) engage antigens using complementarity-determining region (CDR) loops that are either germ line-encoded (CDR1 and CDR2) or somatically rearranged (CDR3). TCR ligands compose a presentation platform (major histocompatibility complex (MHC)) and a variable antigenic component consisting of a short "foreign" peptide. The sequence of events when the TCR engages its peptide-MHC (pMHC) ligand remains unclear. Some studies suggest that the germ line elements of the TCR engage the MHC prior to peptide scanning, but this order of binding is difficult to reconcile with some TCR-pMHC structures. Here, we used TCRs that exhibited enhanced pMHC binding as a result of mutations in either CDR2 and/or CDR3 loops, that bound to the MHC or peptide, respectively, to dissect the roles of these loops in stabilizing TCR-pMHC interactions. Our data show that TCR-peptide interactions play a strongly dominant energetic role providing a binding mode that is both temporally and energetically complementary with a system requiring positive selection by self-pMHC in the thymus and rapid recognition of non-self-pMHC in the periphery.

Study of the cis to trans isomerization of 1-phenyl-2,3-disubstituted tetrahydro-beta-carbolines at C(1). Evidence for the carbocation-mediated mechanism.

The present study was undertaken to shed light on the mechanism of the epimerization of cis-1,2,3-trisubstituted tetrahydro-beta-carbolines into the trans isomers via a potential carbocationic intermediate at C(1). In order to study the pathway involved in C(1)-N(2) bond cleavage, the electronic character of the carbon atom at C-1 was altered by substitution of electron-rich and electron-poor phenyl rings at this position. This provided direct evidence of the effects of charge at the proposed site of the carbocationic intermediate. In this regard, a diverse set of 1-(phenyl substituted)-2-benzyl-3-ethoxycarbonyl-1,2,3,4-tetrahydro-beta-carbolines has been synthesized via the Pictet-Spengler reaction by condensation of l-tryptophan derivatives with electron-poor and electron-rich aromatic aldehydes. The epimers involved in the isomerization mechanism were investigated by dynamic (1)H and (13)C NMR spectroscopic and X-ray crystallographic analyses. The kinetic studies, which involved conversion of cis diastereomers into their trans counterparts, were carried out in dilute TFA/CH(2)Cl(2). The 1-(4-methoxyphenyl) cis diastereomer epimerized at a much faster rate into the corresponding trans diastereomer than the related 1-(4-nitrophenyl) cis diastereomer epimerized. These observations provide support for the carbocationic intermediate in the C(1)-N(2) scission process. The understanding of this epimerization process is of importance when Pictet-Spengler reactions are carried out under acidic conditions during the synthesis of indole alkaloids.