An integrative latent class model of heterogeneous data modalities for diagnosing kidney obstruction.

Radionuclide imaging plays a critical role in the diagnosis and management of kidney obstruction. However, most practicing radiologists in US hospitals have insufficient time and resources to acquire training and experience needed to interpret radionuclide images, leading to increased diagnostic errors. To tackle this problem, Emory University embarked on a study that aims to develop a computer-assisted diagnostic (CAD) tool for kidney obstruction by mining and analyzing patient data comprised of renogram curves, ordinal expert ratings on the obstruction status, pharmacokinetic variables, and demographic information. The major challenges here are the heterogeneity in data modes and the lack of gold standard for determining kidney obstruction. In this article, we develop a statistically principled CAD tool based on an integrative latent class model that leverages heterogeneous data modalities available for each patient to provide accurate prediction of kidney obstruction. Our integrative model consists of three sub-models (multilevel functional latent factor regression model, probit scalar-on-function regression model, and Gaussian mixture model), each of which is tailored to the specific data mode and depends on the unknown obstruction status (latent class). An efficient MCMC algorithm is developed to train the model and predict kidney obstruction with associated uncertainty. Extensive simulations are conducted to evaluate the performance of the proposed method. An application to an Emory renal study demonstrates the usefulness of our model as a CAD tool for kidney obstruction.

fac-99mTc/Re-tricarbonyl complexes with tridentate aminocarboxyphosphonate ligands: suitability of the phosphonate group in chelate ligand design of new imaging agents.

Ligands that coordinate via dianionic phosphonate groups have not been widely utilized in radiopharmaceuticals. N-(phosphonomethyl)iminodiacetic acid (1, PMIDA) and N-(phosphonomethyl)glycine (2, PMG) were investigated as new chelators for the 99mTc/Re-tricarbonyl "core" (fac-M(CO)3, M = 99mTc, Re) present in a major class of radiopharmaceuticals. fac-M(CO)3(PMIDA) and fac-M(CO)3(PMG) complexes were studied by HPLC and 1H/13C/31P NMR methods for M = Re (Re-1 and Re-2) and by HPLC for M = 99mTc ( 99m Tc-1 and 99m Tc-2). Re-1 and 99m Tc-1 complexes exhibit a similar pH-dependent equilibrium between geometric linkage isomers (M-1a and M-1b). However, only one isomer exists for M-2 under all conditions. Structural characterization by X-ray crystallography reveals the presence of a bond between a phosphonate oxygen and the Re(I) center in fac-Re(CO)3(PMG) (Re-2). Detailed comparisons of NMR data for Re-2 conclusively demonstrate that the phosphonate group is coordinated in Re-1b (isomer favored at high pH) but not in Re-1a, which has a dangling N-(phosphonomethyl) group. To our knowledge, Re-1b and Re-2 and their 99mTc analogs are the first well-documented examples of complexes with these metal-tricarbonyl cores having a dianionic phosphonate group directly coordinated in a fac-M(CO)3-O-P grouping. Pharmacokinetic studies using Sprague-Dawley rats reveal that 99m Tc-2 is a robust tracer. Hence, phosphonate groups should be considered in designing 99mTc and 186/188Re radiopharmaceuticals, including agents with bioactive moieties attached to dangling carboxylate or phosphonate groups.

Overall indices for assessing agreement among multiple raters.

The need to assess agreement exists in various clinical studies where quantifying inter-rater reliability is of great importance. Use of unscaled agreement indices, such as total deviation index and coverage probability (CP), is recommended for two main reasons: (i) they are intuitive in a sense that interpretations are tied to the original measurement unit; (ii) practitioners can readily determine whether the agreement is satisfactory by directly comparing the value of the index to a prespecified tolerable CP or absolute difference. However, the unscaled indices were only defined in the context of comparing two raters or multiple raters that assume homogeneity of variances across raters. In this paper, we introduce a set of overall indices based on the root mean square of pairwise differences that are unscaled and can be used to evaluate agreement among multiple raters that often exhibit heterogeneous measurement processes in practice. Furthermore, we propose another overall agreement index based on the root mean square of pairwise differences that is scaled and extends the concept of the recently proposed relative area under CP curve in the presence of multiple raters. We present the definitions of overall indices and propose inference procedures in which bootstrap methods are used for the estimation of standard errors. We assess the performance of the proposed approach and demonstrate its superiority over the existing methods when raters exhibit heterogeneous measurement processes using simulation studies. Finally, we demonstrate the application of our methods using a renal study.

Incorporating fragmentation and non-native species into distribution models to inform fluvial fish conservation.

Fluvial fishes face increased imperilment from anthropogenic activities, but the specific factors contributing most to range declines are often poorly understood. For example, the range of the fluvial-specialist shoal bass (Micropterus cataractae) continues to decrease, yet how perceived threats have contributed to range loss is largely unknown. We used species distribution models to determine which factors contributed most to shoal bass range loss. We estimated a potential distribution based on natural abiotic factors and a series of currently occupied distributions that incorporated variables characterizing land cover, non-native species, and river fragmentation intensity (no fragmentation, dams only, and dams and large impoundments). We allowed interspecific relationships between non-native congeners and shoal bass to vary across fragmentation intensities. Results from the potential distribution model estimated shoal bass presence throughout much of their native basin, whereas models of currently occupied distribution showed that range loss increased as fragmentation intensified. Response curves from models of currently occupied distribution indicated a potential interaction between fragmentation intensity and the relationship between shoal bass and non-native congeners, wherein non-natives may be favored at the highest fragmentation intensity. Response curves also suggested that >100 km of interconnected, free-flowing stream fragments were necessary to support shoal bass presence. Model evaluation, including an independent validation, suggested that models had favorable predictive and discriminative abilities. Similar approaches that use readily available, diverse, geospatial data sets may deliver insights into the biology and conservation needs of other fluvial species facing similar threats.

99mTc-MAG3: Image Wisely.

Purpose To determine if commonly administered doses of technetium 99m (99mTc) mertiatide (MAG3) in the range of 300-370 MBq (approximately 8-10 mCi) contribute to image interpretation and justify the resulting radiation exposure. Materials and Methods The respective institutional review boards approved this HIPAA-compliant study and waived informed consent. Baseline and furosemide 99mTc-MAG3 imaging examinations in 50 patients suspected of having renal obstruction and 48 patients suspected of having renovascular hypertension (RVH) were randomly selected from archived databases and were independently scored by three experienced readers without access to 2-second flow images. Readers were blinded to their original scores, and then they rescored each examination with access to high-activity 2-second flow images. Relative renal function was determined after a low activity (62.9 MBq ± 40.7) baseline acquisition for RVH and a high activity (303.4 MBq ± 48.1) acquisition after administration of enalaprilat. Data were analyzed by using random effects analysis of variance and mean and standard error of the mean for the difference between sets of scores and the difference between relative function measurements. Results There was no significant difference in the scores without flow images compared with blinded scores with high-activity flow images for patients suspected of having obstruction (P = .80) or RVH (P = .24). Moreover, there was no significant difference in the relative uptake measurements after administration of low and high activities (P > .99). Conclusion Administered doses of 99mTc-MAG3 in the range of 300-370 MBq (approximately 8-10 mCi) do not affect the relative function measurements or contribute to interpretation of images in patients suspected of having RVH or obstruction compared with administration of lower doses; unnecessary radiation exposure can be avoided by administering doses in the range of 37-185 MBq as recommended incurrent guidelines. © RSNA, 2017.

Identification of lead compounds for (99m)Tc and (18)F GPR91 radiotracers.

To develop the first radiotracer targeting GPR91, a cell membrane-bound receptor that modulates the cellular response to hyperglycemia and hypoxia, we designed and prepared a small series of compounds based on a published series of 1,8-naphthyridines with high affinity to GPR91. Our approach provides a mechanism to incorporate radioactive atoms ((99m)Tc and (18)F) into the GPR91 pharmacophore as the final synthetic step. Pharmacological assays confirmed lead compounds for (99m)Tc and (18)F GPR91 radiotracers within the series.

Structure and Properties of fac-[Re(I)(CO)3(NTA)](2-) (NTA(3-) = Trianion of Nitrilotriacetic Acid) and fac-[Re(I)(CO)3(L)](n-) Analogues Useful for Assessing the Excellent Renal Clearance of the fac-[(99m)Tc(I)(CO)3(NTA)](2-) Diagnostic Renal Agent.

We previously identified two new agents based on the [(99m)Tc(V)O](3+) core with renal clearances in human volunteers 30% higher than that of the widely used clinical tracer (99m)Tc-MAG3 (MAG3(5-) = penta-anion of mercaptoacetyltriglycine). However, renal agents with even higher clearances are needed. More recently, we changed our focus from the [(99m)Tc(V)O](3+) core to the discovery of superior tracers based on the fac-[(99m)Tc(I)(CO)3](+) core. Compared to (99m)Tc-MAG3, fac-[(99m)Tc(I)(CO)3(NTA)](2-) (NTA(3-) = trianion of nitrilotriacetic acid) holds great promise by virtue of its efficient renal clearance via tubular secretion and the absence of hepatobiliary elimination, even in patients with severely reduced renal function. We report here NMR, molecular (X-ray) structure, and solution data on fac-[Re(I)(CO)3(NTA)](2-) with a -CH2CO2(-) dangling monoanionic chain and on two fac-[Re(I)(CO)3(L)](-) analogues with either a -CH2CONH2 or a -CH2CH2OH dangling neutral chain. In these three fac-[Re(I)(CO)3(L)](n-) complexes, the fac-[Re(I)(CO)3(N(CH2CO2)2)](-) moiety is structurally similar and has similar electronic properties (as assessed by NMR data). In reported and ongoing studies, the two fac-[(99m)Tc(I)(CO)3(L)](-) analogues with these neutral dangling chains were found to have pharmacokinetic properties very similar to those of fac-[(99m)Tc(I)(CO)3(NTA)](2-). Therefore, we reach the unexpected conclusion that in fac-[(99m)Tc(I)(CO)3(L)](n-) agents, renal clearance is affected much more than anticipated by features of the core plus the chelate rings (the [(99m)Tc(I)(CO)3(N(CH2CO2)2)](-) moiety) than by the presence of a negatively charged dangling carboxylate chain.

Clinical decision support systems in myocardial perfusion imaging.

Diagnostic imaging is becoming more complicated, physicians are also required to master an ever-expanding knowledge base and take into account an ever increasing amount of patient-specific clinical information while the time available to master this knowledge base, assemble the relevant clinical data, and apply it to specific tasks is steadily shrinking. Compounding these problems, there is an ever increasing number of aging "Baby Boomers" who are becoming patients coupled with a declining number of cardiac diagnosticians experienced in interpreting these studies. Hence, it is crucial that decision support tools be developed and implemented to assist physicians in interpreting studies at a faster rate and at the highest level of up-to-date expertise. Such tools will minimize subjectivity and intra- and inter-observer variation in image interpretation, help achieve a standardized high level of performance, and reduce healthcare costs. Presently, there are many decision support systems and approaches being developed and implemented to provide greater automation and to further objectify and standardize analysis, display, integration, interpretation, and reporting of myocardial perfusion SPECT and PET studies. This review focuses on these systems and approaches.

Computer assisted interpretation of Tc-99m mercaptoacetyltriglycine diuretic scintigraphy enhances resident performance.

OBJECTIVE: iRENEX is a software module that incorporates scintigraphic and clinical data to interpret 99m Tc- mercaptoacetyltriglycine (MAG3) diuretic studies and provide reasons for their conclusions. Our objectives were to compare iRENEX interpretations with those of expert physicians, use iRENEX to evaluate resident performance and determine if iRENEX could improve the diagnostic accuracy of experienced residents. METHODS: Baseline and furosemide 99m Tc-MAG3 acquisitions of 50 patients with suspected obstruction (mean age ± SD, 58.7 ±â€…15.8 years, 60% female) were randomly selected from an archived database and independently interpreted by iRENEX, three expert readers and four nuclear medicine residents with one full year of residency. All raters had access to scintigraphic data and a text file containing clinical information and scored each kidney on a scale from +1.0 to -1.0. Scores ≥0.20 represented obstruction with higher scores indicating greater confidence. Scores +0.19 to -0.19 were indeterminate; scores ≤-0.20 indicated no obstruction. Several months later, residents reinterpreted the studies with access to iRENEX. Receiver operating characteristic (ROC) analysis and concordance correlation coefficient (CCC) quantified agreement. RESULTS: The CCC among experts was higher than that among residents, 0.84, versus 0.39, respectively, P  < 0.001. When residents reinterpreted the studies with iRENEX, their CCC improved from 0.39 to 0.73, P  < 0.001. ROC analysis showed significant improvement in the ability of residents to distinguish between obstructed and non-obstructed kidneys using iRENEX ( P  = 0.036). CONCLUSION: iRENEX interpretations were comparable to those of experts. iRENEX reduced interobserver variability among experienced residents and led to better agreement between resident and expert interpretations.

Synthesis and characterization of fac-Re(CO)3-aspartic-N-monoacetic acid, a structural analogue of a potential new renal tracer, fac-99mTc(CO)3(ASMA).

The reaction of an aminopolycarboxylate ligand, aspartic-N-monoacetic acid (ASMA), with [Re(CO)3(H2O)3]+ was examined. The tridentate coordination of ASMA to this ReI tricarbonyl precursor yielded fac-Re(CO)3(ASMA) as a mixture of diastereomers. The chemistry is analogous to that of the TcI tricarbonyl complex, which yields fac-99mTc(CO)3(ASMA) under similar conditions. The formation, structure, and isomerization of fac-Re(CO)3(ASMA) products were characterized by HPLC, 1H NMR spectroscopy, and X-ray crystallography. The two major fac-Re(CO)3(ASMA) diastereomeric products each have a linear ONO coordination mode with two adjacent five-membered chelate rings, but they differ in the endo or exo orientation of the uncoordinated acetate group, in agreement with expectations based on previous studies. Conditions have been identified for the expedient isomerization of fac-Re(CO)3(ASMA) to a mixture consisting primarily of one major product. Because different isomeric species typically have different pharmacokinetic characteristics, these conditions may provide for the practical isolation of a single 99mTc(CO)3(ASMA) species, thus allowing the isolation of the isomer that has optimal imaging and pharmacokinetic characteristics. This information will aid in the design of future 99mTc radiopharmaceuticals.

Phylogenomics and species delimitation of the economically important Black Basses (Micropterus).

Informed management and conservation efforts are vital to sustainable recreational fishing and biodiversity conservation. Because the taxonomic rank of species is important in conservation and management strategies, success of these efforts depends on accurate species delimitation. The Black Basses (Micropterus) are an iconic lineage of freshwater fishes that include some of the world's most popular species for recreational fishing and world's most invasive species. Despite their popularity, previous studies to delimit species and lineages in Micropterus suffer from insufficient geographic coverage and uninformative molecular markers. Our phylogenomic analyses of ddRAD data result in the delimitation of 19 species of Micropterus, which includes 14 described species, the undescribed but well-known Altamaha, Bartram's, and Choctaw basses, and two additional undescribed species currently classified as Smallmouth Bass (M. dolomieu). We provide a revised delimitation of species in the Largemouth Bass complex that necessitates a change in scientific nomenclature: Micropterus salmoides is retained for the Florida Bass and Micropterus nigricans is elevated from synonymy for the Largemouth Bass. The new understanding of diversity, distribution, and systematics of Black Basses will serve as important basis for the management and conservation of this charismatic and economically important clade of fishes.

Genomic divergence, local adaptation, and complex demographic history may inform management of a popular sportfish species complex.

The Neosho Bass (Micropterus velox), a former subspecies of the keystone top-predator and globally popular Smallmouth Bass (M. dolomieu), is endemic and narrowly restricted to small, clear streams of the Arkansas River Basin in the Central Interior Highlands (CIH) ecoregion, USA. Previous studies have detected some morphological, genetic, and genomic differentiation between the Neosho and Smallmouth Basses; however, the extent of neutral and adaptive divergence and patterns of intraspecific diversity are poorly understood. Furthermore, lineage diversification has likely been impacted by gene flow in some Neosho populations, which may be due to a combination of natural biogeographic processes and anthropogenic introductions. We assessed: (1) lineage divergence, (2) local directional selection (adaptive divergence), and (3) demographic history among Smallmouth Bass populations in the CIH using population genomic analyses of 50,828 single-nucleotide polymorphisms (SNPs) obtained through ddRAD-seq. Neosho and Smallmouth Bass formed monophyletic clades with 100% bootstrap support. We identified two major lineages within each species. We discovered six Neosho Bass populations (two nonadmixed and four admixed) and three nonadmixed Smallmouth Bass populations. We detected 29 SNPs putatively under directional selection in the Neosho range, suggesting populations may be locally adapted. Two populations were admixed via recent asymmetric secondary contact, perhaps after anthropogenic introduction. Two other populations were likely admixed via combinations of ancient and recent processes. These species comprise independently evolving lineages, some having experienced historical and natural admixture. These results may be critical for management of Neosho Bass as a distinct species and may aid in the conservation of other species with complex biogeographic histories.

Key variables for interpreting 99mTc-mercaptoacetyltriglycine diuretic scans: development and validation of a predictive model.

OBJECTIVE: The purpose of this study was to facilitate interpretation of (99m)Tc-mercaptoacetyltriglycine (MAG3) diuretic scans by identifying key interpretative variables and developing a predictive model for computer-assisted diagnosis. MATERIALS AND METHODS: Ninety-seven studies were randomly selected from an archived database of MAG3 baseline and furosemide acquisitions and scan interpretations (obstruction, equivocal finding, or no obstruction) derived from a consensus of three experts. Sixty-one studies (120 kidneys) were randomly chosen to build a predictive model for diagnosing or excluding obstruction. The other 36 studies (71 kidneys) composed the validation group. The probability of normal drainage (no obstruction) at the baseline acquisition and the probability of no obstruction, equivocal finding, or obstruction after furosemide administration were determined by logistic regression analysis and proportional odds modeling of MAG3 renographic data. RESULTS: The single most important baseline variable for excluding obstruction was the ratio of postvoid counts to maximum counts. Renal counts in the last minute of furosemide acquisition divided by the maximum baseline acquisition renal counts and time to half-maximum counts after furosemide administration in a pelvic region of interest were the critical variables for determining obstruction. The area under the receiver operating characteristic curve (AUC) for predicting normal drainage in the validation sample was 0.93 (standard error, 0.02); sensitivity, 85%; specificity, 93%. The AUC for the diagnosis of obstruction after furosemide administration was 0.84 (standard error, 0.06); sensitivity, 82%; specificity, 83%. CONCLUSION: A predictive system has been developed that provides a promising computer-assisted diagnosis approach to the interpretation of MAG3 diuretic renal scans; this system has also identified the key variables required for scan interpretation.

Head to head comparison of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction.

PURPOSE: 99mTc-tricarbonyl-nitrilotriacetic acid, [99mTc]Tc(CO)3(NTA), is a new 99mTc-renal radiopharmaceutical with a clearance equal to that of 131I-ortho-iodohippuran, [131I]I-OIH. Our purpose was to compare the performance of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction. METHODS: [99mTc]Tc(CO)3(NTA) was prepared with commercially available NTA ligand and CRS Isolink kit, and isolated by HPLC. Eighteen adult patients referred for diuretic renography received an intravenous injection of approximately 40 mg of furosemide 15 min prior to either [99mTc]Tc(CO)3(NTA) or [99mTc]Tc-MAG3 (mean activity of 47 ± 4.4 MBq). Data were acquired for 24 min followed by an anterior image of the liver and gall bladder and a measure of voided volume. Patients received a second furosemide injection equal to one third of the original dose followed fifteen minutes later by administration of the alternate tracer, mean activity of 320 ± 34 MBq. Clearances were measured using a camera-based technique. RESULTS: The clearance of NTA was greater than that of MAG3, 331 ± 146 versus 271 ± 105 mL/min/1.73 m2, respectively, p < 0.0001. The kidney to background ratio for NTA was greater than that of MAG3 for both left and right kidneys, p < 0.001; the 20 min/maximum count ratio was significantly less, p < 0.0001. There was no significant difference in the voiding volumes following NTA and MAG3 administration, 598 ± 237 mL versus 498 ± 170 mL, respectively, p = 0.07. Gall bladder activity was not observed with NTA but was present in 6/17 MAG3 studies. Images and renogram curves were comparable except for two patients where the NTA study excluded obstruction but the MAG3 study suggested an indeterminate or obstructed kidney. CONCLUSIONS: Unlike MAG3, NTA is not eliminated via the hepatobiliary track. Moreover, NTA has a higher kidney to background ratio and more rapid clearance than MAG3. These advantages should allow more robust camera-based clearance measurements and may lead to better discrimination between obstructed and non-obstructed kidneys.

Coordination modes of multidentate ligands in fac-[Re(CO)(3)(polyaminocarboxylate)] analogues of (99m)Tc radiopharmaceuticals. dependence on aqueous solution reaction conditions.

We study Re analogues of (99m)Tc renal agents to interpret previous results at the (99m)Tc tracer level. The relative propensities of amine donors versus carboxylate oxygen donors of four L = polyaminocarboxylate ligands to coordinate in fac-[Re(I)(CO)(3)L](n) complexes were assessed by examining the reaction of fac-[Re(I)(CO)(3)(H(2)O)(3)](+) under conditions differing in acidity and temperature. All four L [N,N-bis-(2-aminoethyl)glycine (DTGH), N,N-ethylenediaminediacetic acid, diethylenetriamine-N-malonic acid, and diethylenetriamine-N-acetic acid] can coordinate as tridentate ligands while creating a dangling chain terminated in a carboxyl group. Dangling carboxyl groups facilitate renal clearance in fac-[(99m)Tc(I)(CO)(3)L](n) agents. Under neutral conditions, the four ligands each gave two fac-[Re(I)(CO)(3)L](n) products with HPLC traces correlating well with known traces of the fac-[(99m)Tc(I)(CO)(3)L](n) mixtures. Such mixtures are common in renal agents because the needed dangling carboxyl group can compete for a coordination site. However, the HPLC separations needed to assess the biodistribution of a single tracer are impractical in a clinical setting. One goal in investigating this Re chemistry is to identify conditions for avoiding this problem of mixtures in preparations of fac-[(99m)Tc(I)(CO)(3)L](n) renal tracers. After separation and isolation of the fac-[Re(I)(CO)(3)L](n) products, NMR analysis of all products and single crystal X-ray crystallographic analysis of both DTGH products, as well as one product each from the other L, allowed us to establish coordination mode unambiguously. The product favored in acidic conditions has a dangling amine chain and more bound oxygen. The product favored in basic conditions has a dangling carboxyl chain and more bound nitrogen. At the elevated temperatures used for simulating tracer preparation, equilibration was facile (ca. 1 h or less), allowing selective formation of one product by utilizing acidic or basic conditions. The results of this fundamental study offer protocols and guidance useful for the design and preparation of fac-[(99m)Tc(I)(CO)(3)L](n) agents consisting of a single tracer.

A Bayesian Latent Class Model to Predict Kidney Obstruction in the Absence of Gold Standard.

Kidney obstruction, if untreated in a timely manner, can lead to irreversible loss of renal function. A widely used technology for evaluations of kidneys with suspected obstruction is diuresis renography. However, it is generally very challenging for radiologists who typically interpret renography data in practice to build high level of competency due to the low volume of renography studies and insufficient training. Another challenge is that there is currently no gold standard for detection of kidney obstruction. Seeking to develop a computer-aided diagnostic (CAD) tool that can assist practicing radiologists to reduce errors in the interpretation of kidney obstruction, a recent study collected data from diuresis renography, interpretations on the renography data from highly experienced nuclear medicine experts as well as clinical data. To achieve the objective, we develop a statistical model that can be used as a CAD tool for assisting radiologists in kidney interpretation. We use a Bayesian latent class modeling approach for predicting kidney obstruction through the integrative analysis of time-series renogram data, expert ratings, and clinical variables. A nonparametric Bayesian latent factor regression approach is adopted for modeling renogram curves in which the coefficients of the basis functions are parameterized via the factor loadings dependent on the latent disease status and the extended latent factors that can also adjust for clinical variables. A hierarchical probit model is used for expert ratings, allowing for training with rating data from multiple experts while predicting with at most one expert, which makes the proposed model operable in practice. An efficient MCMC algorithm is developed to train the model and predict kidney obstruction with associated uncertainty. We demonstrate the superiority of the proposed method over several existing methods through extensive simulations. Analysis of the renal study also lends support to the usefulness of our model as a CAD tool to assist less experienced radiologists in the field.

Spatial sampling bias and model complexity in stream-based species distribution models: A case study of Paddlefish (Polyodon spathula) in the Arkansas River basin, USA.

Leveraging existing presence records and geospatial datasets, species distribution modeling has been widely applied to informing species conservation and restoration efforts. Maxent is one of the most popular modeling algorithms, yet recent research has demonstrated Maxent models are vulnerable to prediction errors related to spatial sampling bias and model complexity. Despite elevated rates of biodiversity imperilment in stream ecosystems, the application of Maxent models to stream networks has lagged, as has the availability of tools to address potential sources of error and calculate model evaluation metrics when modeling in nonraster environments (such as stream networks). Herein, we use Maxent and customized R code to estimate the potential distribution of paddlefish (Polyodon spathula) at a stream-segment level within the Arkansas River basin, USA, while accounting for potential spatial sampling bias and model complexity. Filtering the presence data appeared to adequately remove an eastward, large-river sampling bias that was evident within the unfiltered presence dataset. In particular, our novel riverscape filter provided a repeatable means of obtaining a relatively even coverage of presence data among watersheds and streams of varying sizes. The greatest differences in estimated distributions were observed among models constructed with default versus AICC-selected parameterization. Although all models had similarly high performance and evaluation metrics, the AICC-selected models were more inclusive of westward-situated and smaller, headwater streams. Overall, our results solidified the importance of accounting for model complexity and spatial sampling bias in SDMs constructed within stream networks and provided a roadmap for future paddlefish restoration efforts in the study area.

99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.

UNLABELLED: To develop a (99m)Tc renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard (131)I-o-iodohippurate ((131)I-OIH) and superior to that of (99m)TcO-mercaptoacetyltriglycine, which has a clearance only 50%-60% that of (131)I-OIH, we investigated (99m)Tc-tricarbonyl nitrilotriacetic acid (Na(2)[(99m)Tc(CO)(3)(NTA)]). This radiopharmaceutical, which is based on an aminopolycarboxylate ligand, is formed as a single species and has a dangling carboxylate group favoring tubular transport. METHODS: Na(2)[(99m)Tc(CO)(3)(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na(2)[(99m)Tc(CO)(3)(NTA)] in isotonic saline was assessed for 24 h and was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 degrees C. The biodistribution of Na(2)[(99m)Tc(CO)(3)(NTA)], coinjected with (131)I-OIH as an internal control, was evaluated in 5 normal Sprague-Dawley rats at 10 min, 5 normal Sprague-Dawley rats at 60 min (group A), and 6 rats with renal pedicle ligation at 60 min (group B) after injection. Clearance and extraction fraction studies were conducted in 2 normal Sprague-Dawley rats, and urine and plasma from 2 additional normal rats each were analyzed for metabolites by high-performance liquid chromatography. RESULTS: The radiochemical purity of Na(2)[(99m)Tc(CO)(3)(NTA)] was greater than 99%, the complex was stable for 24 h at physiologic pH, and the challenge experiments showed no degradation. In normal rats, the percentage dose in the urine at 10 and 60 min was 108% +/- 9% and 101% +/- 5%, respectively, that of (131)I-OIH; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na(2)[(99m)Tc(CO)(3)(NTA)] was better retained in the blood and had less excretion into the bowel than did (131)I-OIH (P < 0.01). The plasma clearances of Na(2)[(99m)Tc(CO)(3)(NTA)] and (131)I-OIH were comparable, but the extraction fraction of Na(2)[(99m)Tc(CO)(3)(NTA)] was 93.5% +/- 3.8%, compared with 67.9% +/- 6.1% for (131)I-OIH. Plasma protein binding of Na(2)[(99m)Tc(CO)(3)(NTA)] averaged 67% +/- 7%, and red cell uptake was 7% +/- 2%. CONCLUSION: Na(2)[(99m)Tc(CO)(3)(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of (131)I-OIH.

Re(CO)3([18F]FEDA), a novel 18F PET renal tracer: Radiosynthesis and preclinical evaluation.

INTRODUCTION: Our previous work demonstrated that the 99mTc renal tracer, 99mTc(CO)3(FEDA) (99mTc-1), has a rapid clearance comparable in rats to that of 131I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99mTc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18F renal imaging agent, Re(CO)3([18F]FEDA) (18F-1). Our goal was to develop an efficient one-step method for the preparation of 18F-1 and to compare its pharmacokinetic properties with those of 131I-OIH in rats. METHODS: 18F-1 was prepared by the nucleophilic 18F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131I-OIH as an internal control and by dynamic PET/CT imaging. Plasma protein binding (PPB) and erythrocyte uptake (RCB) were determined and the urine was analyzed for metabolites. RESULTS: 18F-1 was efficiently prepared as a single species with high radiochemical purity (>99%) and it displayed high radiochemical stability in vitro and in vivo. PPB was 87% and RCB was 21%. Biodistribution studies confirmed rapid renal extraction and high specificity for renal excretion, comparable to that of 131I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of 131I-OIH, was 92% and 95% at 10 and 60 min, respectively. All other organs (heart, spleen, lungs) showed a negligible tracer uptake (<0.4% ID). Dynamic microPET/CT imaging demonstrated rapid transit of 18F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [18F]fluoride. CONCLUSIONS: 18F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of 131I-OIH and high in vivo radiochemical stability. Not only is 18F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous 18F/99mTc renal imaging agents with almost identical structures and comparable pharmacokinetic properties. These promising in vivo results warrant subsequent evaluation in humans.

The BEIR VII Estimates of Low-Dose Radiation Health Risks Are Based on Faulty Assumptions and Data Analyses: A Call for Reassessment.

The 2006 National Academy of Sciences Biologic Effects of Ionizing Radiation (BEIR) VII report is a well-recognized and frequently cited source on the legitimacy of the linear no-threshold (LNT) model-a model entailing a linear and causal relationship between ionizing radiation and human cancer risk. Linearity means that all radiation causes cancer and explicitly excludes a threshold below which radiogenic cancer risk disappears. However, the BEIR VII committee has erred in the interpretation of its selected literature; specifically, the in vitro data quoted fail to support LNT. Moreover, in vitro data cannot be considered as definitive proof of cancer development in intact organisms. This review is presented to stimulate a critical reevaluation by a BEIR VIII committee to reassess the validity, and use, of LNT and its derived policies.