Does 99mTc-tilmanocept, as next generation radiotracer, meet with the requirements for improved sentinel node imaging?

INTRODUCTION AND OBJECTIVES: To evaluate the migration of 99mTc-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration. MATERIALS AND METHODS: For 29 primary tumours in 28 patients (mean age: 62y, range: 45-81y) scheduled for SN biopsy planar images were acquired 10 and 120min after administration of 74MBq 99mTc-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT-CT was performed immediately after delayed planar images to enable anatomical lymph node localization. RESULTS: SNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (N=29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2h compared to 15min decreased with an average of 66% (range: 15-96%). SN/non-SN 2h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3-15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%). CONCLUSION: 99mTc-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake. This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of 99mTc-tilmanocept with standard SN radiotracers in larger series of patients is necessary.

The added value of clinical radiopharmacists in nuclear medicine: The example of glomerular filtration rate assessment in kidney donors.

WHAT IS KNOWN AND OBJECTIVES: In Europe, the pharmaceutical supply of chromium-51 has been stopped. However, this isotope is necessary for the evaluation of glomerular filtration rates. It is possible to replace it with technetium-99m, but the validation of this change in the measurement method must be carried out. METHODS: A retrospective analysis of chromium-51 data from January 2018 to January 2019 was performed, followed by a study from January 2019 to January 2020 using the technetium tracer. The patients were different in the both study groups, and none had an eGFR below 50 mL min-1 . A cost analysis was performed. Patient exposure to ionizing radiation was studied for both methods. RESULTS AND DISCUSSION: Seventy-eight patients were included in the study. In total, 42 EDTA-51 Cr and 36 DTPA-99m Tc examinations were conducted and compared. There were no significant differences between the methods used to assess renal function (P = .351). The results of cost analysis and patient radiation exposure were in favour of DTPA-99m Tc examinations. WHAT IS NEW AND CONCLUSION: Within the limitations of a retrospective study of two patient cohorts, there was no significant difference between the results obtained with chromium-51 and technetium-99m tracers. In addition, with the use of DTPA-99m Tc, operating costs and patient exposure to ionizing radiation were reduced, and clinical activity was maintained for the patients' benefit. Radiopharmacists are able to react quickly to supply contingencies, reduce operating costs and maintain the quality of medical examinations.

Glomerular filtration rate: comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA revisited.

The issue of whether 99mTc-DTPA can replace 51Cr-EDTA for measurement of plasma clearance as a surrogate for glomerular filtration rate (GFR) is of great relevance to daily clinical practice. Prompted by the shortage of 51Cr-EDTA we conducted a head-to-head comparison in patients attending our department for GFR determination. The two tracers (3.7 MBq of 51Cr-EDTA and 8 MBq of 99mTc-DTPA) were administered intravenously immediately after each other, and the standard number of blood samples were drawn. Fifty-four patients were enrolled. In 51 of these, single-sample measurement was performed with the following results: GFREDTA was 84.6 ± 23.3 mL/min, GFRDTPA was 84.2 ± 24.7 mL/min. The mean difference was 0.4 ± 2.8 mL/min, p = 0.32, and results based on the two tracers were highly correlated (r = 0.995). GFRDTPA exceeded GFREDTA at high GFR values (difference < 0 at GFREDTA >91.4 mL/min) and vice versa (difference > 0 at GFREDTA < 91.4 mL/min). However, differences fell within few GFR units that most often will have no clinical consequence. We therefore conclude that 99mTc-DTPA can replace 51Cr-EDTA for single-sample determination of GFR in a clinical setting.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.

Intravitreal Pharmacokinetics in Mice: SPECT/CT Imaging and Scaling to Rabbits and Humans.

Preclinical in vivo tests of retinal drug responses are carried out in mice and rats, often after intravitreal injections. However, quantitative pharmacokinetics in the mouse eye is poorly understood. Ocular pharmacokinetics studies are usually done in rabbits. We investigated elimination of three compounds ([99mTc]Tc-pentetate, [111In]In-pentetreotide, [99mTc]Tc-human serum albumin with molecular weights of 510.2 Da, 1506.4 Da, and 66.5 kDa, respectively) from mouse vitreous using imaging with single photon emission computed tomography/computed tomography (SPECT/CT). Increasing molecular weight decreased elimination of the compounds from the mouse eyes. Half-lives of [99mTc]Tc-pentetate, [111In]In-pentetreotide, and [99mTc]Tc-human serum albumin in the mouse eyes were 1.8 ± 0.5 h, 4.3 ± 1.7 h, and 30.0 ± 9.0 h, respectively. These values are 3-12-fold shorter than half-lives of similar compounds in the rabbit vitreous. Dose scaling factors were calculated for mouse-to-rabbit and mouse-to-man translation. They were 27-90 and 38-126, respectively, for intravitreal injections in rabbit and man. We show ocular pharmacokinetic parameters for mice and interspecies scaling factors that may augment ocular drug discovery and development.

Validation of Glomerular Filtration Rate Measurement with Blood Sampling from the Injection Site.

Measurement of glomerular filtration rate (GFR) from the plasma clearance of a radionuclide-labeled tracer is reliable and accurate. However, to avoid contamination of the blood samples with radioactivity remaining at the injection site, venepuncture at 2 or more sites is required: one for tracer administration and the others for blood sampling. This requirement is uncomfortable for patients, particularly when venous access is difficult. The objective of this study was to validate the use of a single site of venous access in combination with injection site imaging, for GFR measurement. Methods: Twenty-two adults (≥18 y) who were referred for GFR determination were included prospectively. GFR was measured from the plasma clearance of 99mTc-diethylenetriaminepentaacetic acid according to international guidelines. After administration of the tracer through an intravenous cannula, a 60-s static image of the injection site was acquired. A second intravenous cannula was inserted into the contralateral arm. Venous blood samples were collected at 2, 3, and 4 h after administration of the radiotracer from both the injection site (experimental) and the contralateral arm (conventional). GFR was calculated using slope-intercept and single-sample methods. The median conventional and experimental plasma counts (decay- and background-corrected) were compared for the 2-, 3-, and 4-h venous samples. Conventional and experimental GFRs were then compared, with a more than 10% difference between conventional and experimental GFRs being regarded as significant. Results: Four individuals had visible residual activity at the injection site. The median 2-h counts differed significantly between the conventional and experimental sampling sites (P = 0.007), whereas no significant difference was found at 3 or 4 h. When there was a clear injection site image, the difference between the experimental and conventional GFRs was more than 10% in 1 case for single-sample GFR but less than 8% in all cases for slope-intercept GFR. Conclusion: In cases with clear injection site images, slope-intercept GFR calculated after injection site blood sampling showed no clinically significant difference from conventional contralateral-arm sampling.

Evaluation of BBB permeable nucleolipid (NLDPU): A di-C15-ketalised palmitone appended uridine as neuro-tracer for SPECT.

Despite being in routine for onco-diagnostics for years, the applicability of nucleosidic molecular imaging probes is severely restricted in neurological applications due to their low permeability across blood-brain-barrier (BBB). For extending nucleoside tracers utility for neuro-onco early diagnostics, suitable modification which enhances their BBB permeation needs investigation. Among various modifications, lipidization of nucleosides has been reported to enhance cellular permeability. Extending the concept, the aim was to exemplify the possibility of lipidized nucleosides as potential brain tracer with capability to cross intact BBB and evaluate as metal based neuro-imaging SPECT agent. Uridine based non-lipidic (NSDAU) and di-C15-ketal appended lipidic (NLDPU) ligands were conjugated to chelator, DTPA (DTPA-NSDAU and DTPA-NLDPU) using multi-step chemistry. The ligands were evaluated in parallel for comparative physical and biological parameters. Additionally, effects of enhanced lipophilicity on UV-absorption, acid strength, fluorescence and non-specific protein binding were evaluated. Fluorescence quenching of BSA indicated appreciable interaction of DTPA-NLDPU with protein only above 10 mM without inducing conformational changes. In addition, DTPA-NLDPU was found to be haematocompatible and cytocompatible with low dose-dependent toxicity in HEK-cells. The chelator DTPA was used for 99mTc-complexation for SPECT imaging. Optimized 99mTc-radiolabeling parameters resulted in quantitative (≥97%) labeling with good stability parameters in in-vitro serum and cysteine challenge studies. We demonstrate that the nucleolipid radiotracer (99mTc-DTPA-NLDPU) was successfully able to permeate the BBB with brain uptake of 0.2% ID/g in normal mice as compared to 0.06% ID/g uptake of 99mTc-DTPA-NSDAU at 5 min. Blood kinetics indicate biphasic profile and t1/2(distribution) 46 min for 99mTc-DTPA-NLDPU. The preferential accumulation of 99mTc-DTPA-NLDPU in brain tumor intracranial xenograft indicate the targeting capability of the nucleoside. We conclude that as first-of-its-kind, this work presents the potential of the biocompatible nucleolipidic system for brain targeting and early diagnostics.

Molecular Imaging of the Glomerulus via Mesangial Cell Uptake of Radiolabeled Tilmanocept.

An unmet need for the clinical management of chronic kidney disease is a predictive tool of kidney function during the first decade of the disease, when there is silent loss of glomerular function. The objective of this study was to demonstrate receptor-mediated binding of tilmanocept to CD206 within the kidney and provide evidence of kinetic sensitivity of this binding to renal function. Methods: Rats were positioned in a PET scanner with the liver and kidneys within the field of view. After an intravenous injection of 68Ga-IRDye800-tilmanocept, using 1 of 2 scaled molar doses (0.02 nmol/g, n = 5; or 0.10 nmol/g, n = 5), or coinjection (n = 3) of 68Ga-IRDye800-tilmanocept (0.10 nmol/g) and unlabeled tilmanocept (5.0 nmol/g), or a negative control, 68Ga-IRDye800-DTPA-galactosyl-dextran (0.02 nmol/g, n = 5), each animal was imaged for 20 min followed by a whole-body scan. Frozen kidney sections were stained for podocytes and CD206 using immunofluorescence. Molecular imaging of diabetic db/db mice (4.9 wk, n = 6; 7.3 wk, n = 4; 13.3 wk, n = 6) and nondiabetic db/m mice (n = 6) was performed with fluorescence-labeled 99mTc-tilmanocept (18.5 MBq, 2.6 nmol). Thirty minutes after injection, blood, liver, kidneys, and urine were assayed for radioactivity. Renal time-activity curves were generated. Results: Rat PET whole-body images and time-activity curves of 68Ga-IRDye800-tilmanocept demonstrated receptor-mediated renal accumulation with evidence of glomerular uptake. Activity within the renal cortex persisted during the 40-min study. Histologic examination demonstrated colocalization of CD206 and IRDye800-tilmanocept within the glomerulus. The glomerular accumulation of the coinjection and the negative control studies were significantly less than the CD206-targeted agent. The db/db mice displayed a multiphasic renal time-activity curve with high urinary bladder accumulation; the nondiabetic mice exhibited renal uptake curves dominated by a single phase with low bladder accumulation. Conclusion: This study demonstrated receptor-mediated binding to the glomerular mesangial cells and kinetic sensitivity of tilmanocept to chronic renal disease. Given the role of mesangial cells during the progression of diabetic nephropathy, PET or SPECT renal imaging with radiolabeled tilmanocept may provide a noninvasive quantitative assessment of glomerular function.

Heterogeneous liver uptake of Tc-99m-GSA as quantified through SPECT/CT helps to evaluate the degree of liver fibrosis: A retrospective observational study.

Tc-99m-galactosyl human serum albumin (GSA) scintigraphy is used to assess the hepatic functional reserve, and allows for visual assessment of the residual hepatocyte distribution on single-photon emission computed tomography/computed tomography (SPECT/CT) images. The association between heterogeneous liver uptake of Tc-99m-GSA and liver fibrosis remains to be studied in detail. We analyzed this association.Fifty-one patients with chronic hepatobiliary disease undergoing a Tc-99m-GSA scintigraphy were included in this study. The receptor (LHL15) and blood clearance (HH15) indexes (the uptake ratios of the liver and heart) were obtained from dynamic planar images. The liver uptake count maximum-to-mean ratio (LUC Max/Mean) was calculated from single-photon emission computed tomography/computed tomography (SPECT/CT) images as an indicator of the Tc-99m-GSA liver uptake heterogeneity. We assessed the relationship between these quantified values and liver fibrosis.There were 30 Child-Pugh classification grade A patients, 16 grade B patients, and 5 grade C patients. Among the 30 patients whose liver histopathology was evaluable, those with advanced liver fibrosis (F2-4) had a lower LHL15 than those with mild liver fibrosis (F0-1) (median, 0.90 vs. 0.92, P = .04), and a higher LUC Max/Mean (median, 1.80 vs. 1.70, P = .02). The multivariate analysis identified platelets (P = .04) and the LUC Max/Mean (P = .04) as contributing factors of advanced liver fibrosis.These findings suggest that Tc-99m-GSA SPECT/CT can be used not only to assess the hepatic functional reserve, but also to evaluate a degree of liver fibrosis.

MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney donors. / MDRD o CKD-EPI en la estimación del filtrado glomerular del donante renal vivo.

INTRODUCTION: The evaluation of the measured Glomerular Filtration Rate (mGFR) or estimated Glomerular Filtration Rate (eGFR) is key in the proper assessment of the renal function of potential kidney donors. We aim to study the correlation between glomerular filtration rate estimation equations and the measured methods for determining renal function. MATERIAL AND METHODS: We analysed the relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene-triamine-pentaacetate) and those estimated by the four-variable Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a series of living donors at our institution. RESULTS: We included 64 donors (70.6% females; mean age 48.3±11 years). Baseline creatinine was 0.8±0.1 mg/dl and it was 1.1±0.2 mg/dl one year after donation. The equations underestimated GFR when measured by Tc99m-DTPA (MDRD4-9.4 ± 25ml/min, P<.05, and CKD-EPI-4.4 ± 21ml/min). The correlation between estimation equations and the measured method was superior for CKD-EPI (r=.41; P<.004) than for MDRD4 (r=.27; P<.05). eGFR decreased to 59.6±11 (MDRD4) and 66.2±14ml/min (CKD-EPI) one year after donation. This means a mean eGFR reduction of 28.2±16.7 ml/min (MDRD4) and 27.31±14.4 ml/min (CKD-EPI) at one year. CONCLUSIONS: In our experience, CKD-EPI is the equation that better correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening purposes.

Dosimetry of 99mTc (DTPA, DMSA and MAG3) used in renal function studies of newborns and children.

The dose to kidneys of newborns and 1-year old children was calculated using the MIRD methodology. In order to perform renal studies radiopharmaceutical like 99mTc-DTPA, 99m Tc-MAG3 and 99mTc-DMSA are used. Here, besides the anatomic and structure information of kidneys another data are provided in benefit of patient, however during the radioisotope decay emitted radiations delivers, totally or partially, their energy. Therefore is important to estimate the internal radiation dose of the organs. The largest dose to kidneys comes from the self-dose and it is due to the charged particles emitted during 99mTc decay. From the three radiopharmaceutical here used the largest dose to kidneys is due to 99mTc-DMSA, and the smaller dose is due to 99mTc-MAG3.

Primary radiation dosimetry of a novel PET radiopharmaceutical 68Ga-NODAGA-glycine in comparison with 99mTc-DTPA in renal studies.

OBJECTIVE: In this study, we tried to estimate human absorbed dose of 68Ga-NODAGA-glycine as a new potential positron emission tomography (PET) renal agent based on the biodistribution data reported in healthy rats, and compare our estimation with the available absorbed dose data from technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA). SUBJECTS AND METHODS: The medical internal radiation dose (MIRD) formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. S factor calculated by Monte-Carlo N-particle (MCNP) simulation and also this factor has been taken from the tables presented in MIRD pamphlet No.11. Hence, two radiation absorbed dose were calculated for organs. RESULTS: Our dose prediction shows that an 185MBq injection of gallium-68-1,4,7-triazacyclononane-1-γ-glutamylglycine-4,7-diacetic acid (68Ga-NODAGA-glycine) in humans might result in an estimated absorbed dose of 0.063mGy in the whole body when S factor calculated by MCNP simulation. The highest absorbed doses are observed in kidneys, lungs, spleen, liver, and red marrow with 3.510, 0.453, 0.335, 0.268, and 0.239mGy, respectively. In addition to, the estimated absorbed dose for total body after injection of 185MBq of 68Ga-NODAGA-glycine is 0.053mGy when S factor has been taken from MIRD pamphlet No.11. The highest absorbed doses are observed in kidneys, lungs, liver, spleen, and red marrow with 3.110, 0.438, 0.209, 0.203, and 0.203mGy, respectively. Comparison between human absorbed dose estimation for 68Ga-NODAGA-glycine and 99mTc-DTPA indicated that the absorbed dose of the most organs after injection of 99mTc-DTPA is higher than the amount after 68Ga-NODAGA-glycine. CONCLUSION: The results showed that 68Ga-NODAGA-glycine delivers lower dose to the patients. Also due to its application in PET (which offers higher sensitivity and spatial resolution compared to planar or SPET), 68Ga-NODAGA-glycine would be a superior choice than 99mTc-DTPA for renography and impose less radiation doses to patients.

Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

BACKGROUND: High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). METHODS: Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo®; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer®; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow®; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. RESULTS: Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. CONCLUSIONS: In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

A Trans-Nasal Aerosol Delivery Device for Efficient Pulmonary Deposition.

BACKGROUND: Efficient delivery of aerosols to the lungs via the nasal route has been difficult to achieve, but it may offer benefits over the traditional oral route for a range of patient populations. Because slow, continuous delivery of short-acting agents could improve safety, tolerability, compliance, and efficacy when compared with the rapid, intermittent aerosol treatments delivered by mouthpiece or mask, a novel trans-nasal pulmonary aerosol delivery (tPAD) device was developed. The tPAD incorporates an aerosol particle-size selection chamber and a custom nasal cannula that are specifically optimized for aerosol delivery to the lung via the nasal route. The tPAD device produced a steady aerosol output (∼2 mL/h) from an optimized nasal cannula with negligible rainout in the cannula for up to 8 hours. The generated aerosol particles were small enough to minimize nasal deposition [volume median diameter (VMD) = 1.4 µm]. METHODS: In this proof-of-concept study, gamma scintigraphy was used to quantitate deposition efficiency of 99mTc-labeled DTPA in 7% NaCl (hypertonic saline) in healthy human subjects (n = 6) during a short dosing period (15 minutes). A comparison was made with a standard oral jet nebulizer in the same subjects. RESULTS: The tPAD device achieved high pulmonary deposition (39% ± 8%), based on emitted dose, and matched that of the oral jet nebulizer (36% ± 9%). Low fractions of aerosol deposition in the head and nose region were observed for tPAD (6% ± 6%) and jet nebulizer deliver (1% ± 1%) as well. CONCLUSIONS: A profile of high pulmonary deposition efficiency and low nasal dose may enable the sustained use of the tPAD platform with a variety of therapeutic agents for a range of pulmonary disorders.

Determination of Glomerular Filtration Rate with CT Measurement of Renal Clearance of Iodinated Contrast Material versus 99mTc-DTPA Dynamic Imaging "Gates" Method: A Validation Study in Asymmetrical Renal Disease.

Purpose To validate a computed tomographic (CT) glomerular filtration rate (GFR) measurement and compare it with renal dynamic imaging GFR obtained by using the "Gates" method, with dual plasma sampling technetium 99m (99mTc) diethylenetriaminepenta-acetic acid (DTPA) clearance ("true GFR") as the reference standard. Materials and Methods This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Forty-two patients with unilateral renal disease were included. Single-kidney CT GFR was calculated as excretory phase whole-kidney CT number enhancement divided by the area under the time-attenuation curve for the aorta, multiplied by (1 - hematocrit level). The CT GFR was then obtained by summing the result of the two sides. The true GFR and the Gates GFR were measured by using a single injection of 99mTc-DTPA. The CT GFR and Gates GFR were respectively compared with the true GFR by using a paired t test and linear regression analysis. Results The difference between CT GFR (mean ± standard deviation, 96.02 mL/min ± 23.11) and true GFR (90.50 mL/min ± 21.46) was 5.51 mL/min ± 6.96 (P < .001), demonstrating 6.09% systemic overestimation. The difference between Gates GFR (93.93 mL/min ± 26.97) and true GFR was 3.42 mL/min ± 16.10 (P = .176). Linear regression findings confirmed the association between CT GFR (y-axis) and true GFR (x-axis) and between Gates GFR (y-axis) and true GFR (x-axis) (P < .001 for both). Both regression lines paralleled the diagonal (intercept = 0 and slope = 1) (P = .599 and P = .945, respectively). The 95% confidence interval of the former was above the diagonal, confirming the systemic overestimation. The standard deviations of residuals of both linear regressions were 7.02 mL/min and 16.30 mL/min, respectively, demonstrating smaller deviation of the CT GFR (P < .001). Conclusion The proposed CT GFR measurement was validated in this study and was proved to be more accurate than the Gates method despite slight (6.09%) systemic overestimation. © RSNA, 2016 Online supplemental material is available for this article.

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals / Efeitos da pressão expiratória positiva na depuração pulmonar do ácido dietilenotriaminopentacético marcado com tecnécio-99m em aerossol em indivíduos saudáveis

ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects.

RESUMO Objetivo: Avaliar os efeitos da pressão expiratória positiva (PEP) na permeabilidade da membrana epitelial pulmonar em indivíduos saudáveis. Métodos: Foi avaliada uma coorte de 30 indivíduos saudáveis (15 homens e 15 mulheres), com média de idade de 28,3 ± 5,4 anos, média da relação VEF1/CVF de 0,89 ± 0,14 e média de VEF1 de 98,5 ± 13,1% do previsto. Os indivíduos foram submetidos a cintilografia pulmonar por inalação de radioaerossol de ácido dietilenotriaminopentacético marcado com tecnécio-99m (99mTc-DTPA em inglês) em dois estágios: durante respiração espontânea e durante respiração com uma máscara de PEP de 10 cmH2O (n = 10), 15 cmH2O (n = 10) ou 20 cmH2O (n = 10). O 99mTc-DTPA foi nebulizado por 3 min, e sua depuração foi registrada por cintilografia por um período de 30 min durante respiração espontânea e por um período de 30 min durante a respiração com uma máscara de PEP. Resultados: A depuração pulmonar do 99mTc-DTPA foi significativamente menor quando PEP foi aplicada a 10 cmH2O (p = 0,044), 15 cmH2O (p = 0,044) e 20 cmH2O (p = 0,004), em comparação com a observada durante a respiração espontânea. Conclusões: Nossos achados indicam que o uso de PEP nos níveis testados pode induzir um aumento na permeabilidade da membrana epitelial pulmonar e no volume pulmonar em indivíduos saudáveis.

The new Asian modified CKD-EPI equation leads to more accurate GFR estimation in Chinese patients with CKD.

OBJECTIVE: To verify whether the new Asian modified CKD-EPI equation improved the performance of original one in determining GFR in Chinese patients with CKD. METHOD: A well-designed paired cohort was set up. Measured GFR (mGFR) was the result of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma sample clearance method. The estimated GFR (eGFR) was the result of the CKD-EPI equation (eGFR1) and the new Asian modified CKD-EPI equation (eGFR2). The comparisons were performed to evaluate the superiority of the eGFR2 in bias, accuracy, precision, concordance correlation coefficient and the slope of regression equation and measure agreement. RESULTS: A total of 195 patients were enrolled and analyzed. The new Asian modified CKD-EPI equation improved the performance of the original one in bias and accuracy. However, nearly identical performance was observed in the respect of precision, concordance correlation coefficient, slope of eGFR against mGFR and 95 % limit of agreement. In the subgroup of GFR < 60 mL min-1/1.73 m2, the bias of eGFR1 was less than eGFR2 but they have comparable precision and accuracy. In the subgroup of GFR > 60 mL min-1/1.73 m2, eGFR2 performed better than eGFR1 in terms of bias and accuracy. CONCLUSION: The new Asian modified CKD-EPI equation can lead to more accurate GFR estimation in Chinese patients with CKD in general practice, especially in the higher GFR group.

Time Varying Apparent Volume of Distribution and Drug Half-Lives Following Intravenous Bolus Injections.

We present a model that generalizes the apparent volume of distribution and half-life as functions of time following intravenous bolus injection. This generalized model defines a time varying apparent volume of drug distribution. The half-lives of drug remaining in the body vary in time and become longer as time elapses, eventually converging to the terminal half-life. Two example fit models were substituted into the general model: biexponential models from the least relative concentration error, and gamma variate models using adaptive regularization for least relative error of clearance. Using adult population parameters from 41 studies of the renal glomerular filtration marker 169Yb-DTPA, simulations of extracellular fluid volumes of 5, 10, 15 and 20 litres and plasma clearances of 40 and 100 ml/min were obtained. Of these models, the adaptively obtained gamma variate models had longer times to 95% of terminal volume and longer half-lives.

Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides.

Feasibility of radiolabeled small molecule permeability as a quantitative measure of microbicide candidate toxicity.

OBJECTIVE: To determine the feasibility of using quantitative changes in vaginal permeability to small molecules as a measure of candidate microbicide toxicity. STUDY DESIGN: Controlled, open-labeled, prospective study. Seven healthy women received a single vaginal dose of hydroxyethylcellulose gel (HEC), nonoxynol-9 (N-9) or K-Y Jelly. Each gel was radiolabeled with a small molecule ((99m)Tc-DTPA) followed by 12-h blood and urine collection. Pharmacokinetic (PK) parameters of (99m)Tc-DTPA were calculated to compare the impact of each gel on vaginal permeability. Each woman served as her own control. The Friedman test with post hoc Wilcoxon test was used to detect differences among the gels. RESULTS: Vaginal permeability of (99m)Tc-DTPA was highest for the N-9 radiolabel. N-9 plasma area under the concentration curve was 2.7-fold higher (p=.04), and peak concentration was threefold higher (p=.04) compared to HEC. There were no significant PK parameter differences between HEC and K-Y Jelly or between N-9 and K-Y Jelly. Cumulative dose-adjusted median (interquartile range) 12-h timed urine gamma activity was 66.70 × 10(-4)µCi (27.90-152.00) following HEC dosing, 103.00 × 10(-4)µCi (98.20-684.00) following N-9 gel dosing and 20.30 × 10(-4)µCi (11.10-55.90) following K-Y gel dosing. The differences between urine HEC and K-Y Jelly (p=.047) and between N-9 and K-Y Jelly (p=.016) were statistically significant. CONCLUSIONS: It is feasible to measure differences in vaginal permeability among vaginal gels using a radiolabeled small molecule, though there are permeability differences that require a nuanced understanding of gel composition to interpret the results. IMPLICATIONS: Establishing the safety of both vehicle and active pharmaceutical ingredient is an essential task in microbicide development, to be determined as soon as possible. This study suggests that a combination of microbicide toxicity assessments, that is, cervicovaginal permeability, inspection and histopathology, may need to be studied simultaneously.