How much time is enough? Sentinel lymph node mapping time depends on the radiotracer agent.

BACKGROUND: In 2014, technetium-99m tilmanocept (TcTM) replaced technetium-99m sulfur colloid (TcSC) as the standard lymphoscintigraphy (LS) mapping agent in melanoma patients undergoing sentinel lymph node biopsy (SLNB). The aim of this study was to examine differences in mapping time, intra-operative identification of sentinel lymph node (SLN), and false negative rate (FNR) between patients who underwent SLNB with TcTM compared to TcSC. METHODS: Patients who underwent SLNB between 2010 and 2018 were retrospectively identified. Patient demographic, tumor, and imaging data was stratified by receipt of TcSC (n = 258) or TcTM (n = 133). Student's t test and χ2 test were used to compare characteristics and outcomes. RESULTS: Both cohorts were similar in demographic, primary tumor characteristics, and total number of SLN identified (TcTM 3.56 vs. TcSC 3.28, p = 0.244). TcTM was associated with significantly shorter LS mapping times (51.8 vs. 195.1 min, p < 0.01). There was no significant difference in the number of patients with positive SLN (TcTM 11.3 vs. TcSC 17.4%, p = 0.109) and the FNR was similar between both groups (TcTM 25% vs. TcSC 22%). CONCLUSION: TcTM was associated with significantly shorter LS mapping time while identifying similar numbers of SLN. Our results support further study to ensure similar FNR and oncologic outcomes between agents.

A receptor-binding radiopharmaceutical for imaging of traumatic brain injury in a rodent model: [99mTc]Tc-tilmanocept.

INTRODUCTION: Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [99mTc]Tc-tilmanocept is a receptor-binding radiopharmaceutical FDA-approved for sentinel lymph node mapping. We hypothesize that after an intravenous (i.v.) injection, [99mTc]Tc-tilmanocept, will traverse a disrupted BBB and bind to CD206-bearing microglial cells. METHODS: Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naïve controls (n = 4). IRDye800CW-labeled [99mTc]Tc-tilmanocept (0.15 nmol per gram body weight) and FITC-labeled bovine serum albumin (FITC-BSA) were injected (i.v.) into each mouse. Mice were imaged with a high-resolution gamma camera for 45 min. Immediately after imaging, the brains were perfused with fixative, excised, imaged with a fluorescence scanner, assayed for radioactivity, and prepared for histology. RESULTS: In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histo-microscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [99mTc]Tc-tilmanocept uptake value from nuclear imaging and the maximum pixel intensity from fluorescence imaging of the TBI group (1.12 ±â€¯0.12 and 2288 ±â€¯278 a.u., respectively) were significantly (P < 0.04) higher than the sham group (0.64 ±â€¯0.28 and 1708 ±â€¯101 a.u., respectively) and the naive group (0.76 ±â€¯0.24 and 1643 ±â€¯391 a.u., respectively). The mean [99mTc]Tc-tilmanocept scaled uptake in the TBI brains (0.058 ±â€¯0.013%/g) was significantly (P < 0.010) higher than the scaled brain uptake of the sham group (0.031 ±â€¯0.011%/g) and higher (P = 0.04) than the uptake of the naïve group (0.020 ±â€¯0.002%/g). Fluorescence microscopy demonstrated increased uptake of the IRDye800CW-tilmanocept and FITC-BSA in the TBI brain regions. CONCLUSION: [99mTc]Tc-tilmanocept traverses disrupted blood-brain barrier and localizes within the injured region. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [99mTc]Tc-tilmanocept could serve as an imaging biomarker for TBI-associated neuroinflammation and any disease process that involves a disruption of the blood-brain barrier.

Repeatability of glomerular filtration rate studies performed using 99mTc-DTPA in a population including cancer patients.

OBJECTIVE: Glomerular filtration rate (GFR) measurement remains an integral investigation in clinical practice and is particularly important in the prediction and follow-up of renal side-effects of nephrotoxic chemotherapy in cancer patients. Knowing the coefficient of variation (CV) of a test is vital for the correct interpretation of serial studies. Recent difficulties with 51Cr-EDTA availability have renewed interest in 99mTc-DTPA, but there is a paucity of data on the test-retest variability of this radiopharmaceutical. Furthermore, the authors are unaware of published repeatability data in cancer patients. The aim of this study was to determine the CV of repeat 99mTc-DTPA GFR measurements in a clinical patient population that included cancer patients. METHODS: Patients who had undergone ≥2 GFR studies at our department between January 2009 and December 2019 were retrospectively identified. Patients with chronic kidney disease and those who had received chemotherapy, radiotherapy or surgery between measurements were excluded. The CV for each patient was calculated and the mean CVs of cancer and prospective renal donor groups were calculated and compared. RESULTS: Fifty-four patients were included in the final analysis. The mean CV in the cancer group (38 patients) was 8.5% [95% confidence interval (CI) 6.9-10.2%] and in the renal donor group (16 patients) 7.1% (95% CI 4.2-10.1%). These figures did not differ significantly (P = 0.37). The groups were combined to calculate the final overall mean CV of 8.1% (95% CI 6.7-9.6%). CONCLUSION: In both non-cancer and cancer patients the CV of GFR studies performed with 99mTc-DTPA was comparable with mostly 51Cr-EDTA figures presented in literature.

Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.

BACKGROUND: Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells. METHODS: To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR-/- knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of 99mTc-DTPA, an imaging marker of blood-brain barrier permeability. RESULTS: In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between 99mTc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR-/- knockout mice were protected against indoxyl sulfate-induced blood-brain barrier disruption and cognitive impairment. CONCLUSIONS: AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD.

In vivo deposition study of a new generation nebuliser utilising hybrid resonant acoustic (HYDRA) technology.

Conventional nebulisation has the disadvantages of low aerosol output rate and potential damage to macromolecules due to high shear (jet nebulisation) or cavitation (ultrasonic nebulisation). HYDRA (HYbriD Resonant Acoustics) technology has been shown to overcome these problems by using a hybrid combination of surface and bulk sound waves to generate the aerosol droplets. We report the first in vivo human lung deposition study on such droplets. Twelve healthy adult subjects inhaled saline aerosols radiolabelled with technetium-99 m complexed with diethylene triamine penta-acetic acid (99mTc-DTPA). The distribution of the aerosolised droplets in the lungs was imaged by single photon emission computed tomography combined with low dose computed tomography (SPECT/CT). The volume median diameter and geometric standard deviation of the droplets were 1.32 ± 0.027 µm and 2.06 ± 0.040, respectively. The mean delivery efficiency from the nebuliser into the body was 51.2%. About 89.1 ± 4.3% and 2.3 ± 1.4% of the inhaled radiolabelled dose deposited in the lungs and oropharynx, respectively. The deposition was symmetrical and diffusive between the two lungs, with a mean penetration index of 0.82. Thus, the prototype HYDRA nebuliser showed excellent in vivo aerosol deposition performance, demonstrating its potential to be further developed for clinical applications.

Determination of the glomerular filtration rate in patients with type 2 diabetes: An assessment of the agreement between 51Cr-EDTA plasma clearance and 99mTc-DTPA plasma clearance, 99mTc-DTPA renography and plasma creatinine prediction equation.

AIMS: To investigate the agreement of glomerular filtration rate (GFR) determination between 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) plasma clearance (GFREDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance (GFRDTPA), the Gates 99mTc-DTPA renographic method (GFRGates) and the serum creatinine Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI, GFRSCr) in patients with type 2 diabetes mellitus (T2DM). METHODS: Ninety-nine T2DM patients underwent GFR determinations simultaneously with 51Cr-EDTA and 99mTc-DTPA (using the slope-intercept technique and the Brochner-Mortensen correction) and also with GFRGates and GFRSCr. RESULTS: In the comparison between GFREDTA versus GFRDTPA, GFRGates and GFRSCr, the Bland-Altman statistic provided 0.0 ± 13.2, 17.4* ± 28.8 and -5.9* ± 30.1 (*p < 0.001 for the difference from 0). Lin's concordance correlation coefficient showed substantial (0.976), poor (0.737) and poor (0.872) agreement, respectively. The proportion of the index results within the 30% and 10% of GFREDTA measurements were 95% and 74% for GFRDTPA, 53% and 19% for GFRGates, and 83% and 26% for GFRSCr, respectively. CONCLUSION: In T2DM patients, a clinically acceptable agreement is demonstrated between 51Cr-EDTA and 99mTc-DTPA plasma clearance for GFR measurements, suggesting conditional interchangeability between those compounds. Both the CKD-EPI prediction equation and the Gates' renographic method cannot assess GFR reliably, the latter appearing less unfailing than the former.

The displacement study of 99m Tc-DTPA-Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking.

The 99m Tc-DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99m Tc-DTPA have never been characterized. This study will cover in vitro the binding rates of 99m Tc-DTPA on HSA and the 99m Tc-DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99m Tc-DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99m Tc-DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99m Tc-DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99m Tc-DTPA binding. 99m Tc-DTPA could bind to human serum albumin in many locations in site I and I-II, but strongly bound to site I through hydrogen bonds.

Validation of the full-age spectrum equation in the approximation of glomerular filtration rate in Chinese patients with chronic kidney disease.

Introduction: To investigate the validity of the full age spectrum (FAS) equation in determining the glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to compare the performance of FAS equation and the technetium-99m-diethylene triamine pentaacetic acid (Tc-99m-DTPA) renal dynamic imaging method. Methods: The GFR was determined by three methods in the same day: (a) Tc-99m-DTPA dual plasma sample clearance method (mGFR); (b) FAS equation (eGFR1); (c) Tc-99m-DTPA renal dynamic imaging method (eGFR2). The mGFR was used as the reference standard. The Bland-Altman method, concordance correlation coefficient and regression equation were applied to evaluate the validity of the estimated glomerular filtration rate (eGFR). The bias, precision and accuracy were analyzed to compare the performances of eGFR1 and eGFR2. Results: A total of 162 subjects were enrolled in this study. The eGFR1 was correlated well with mGFR (concordance correlation coefficient was 0.896, p < 0.0001) and the regression equation was mGFR = -0.374 + 1.029eGFR1 (p < 0001). The Bland-Altman analysis proved good agreement between the eGFR1 and mGFR. In comparison with eGFR2, the eGFR1 showed better performance on bias (-1.22 vs. 8.92, p < 0001), precision (15.69 vs. 18.36, p = 0.047) and 30% accuracy (75.31% vs. 59.26%, p = 0.0009) in all participants. Conclusions: The FAS equation is valid in determining the glomerular filtration rate in Chinese patients with chronic kidney disease. The Tc-99m-DTPA renal dynamic imaging method is less accurate than the FAS equation and cannot be employed as the reference method in assessing the performance of FAS equation.

[99mTc]Tilmanocept Lymphscintigraphy after inconclusive [99mTc]Nanocolloid Scan in Breast Cancer.

Lymphatic mapping for identification and subsequent removal of the sentinel lymph node (SLN) is an established procedure in breast cancer and cutaneous melanoma to minimize the extent of surgery (and thus, associated morbidity), simplify histopathological processing and subsequently provide prognostic information and help choose the optimal patient management. Established methods for SLN mapping include visual identification of nodal staining after peritumoral injection of a (blue) dye or the use of lymphoscintigraphy with technetium-labelled nanocolloid. In experienced hands, success rates for both methods exceed 95 %, nonetheless in some patients they fail despite correct application and imaging techniques. Potential reasons for false-negative SLN detection rates -beyond poor tracer injection technique or imaging of the wrong nodal basin- include inadequate pathologic examination of the SLN or complete replacement of the SLN with neoplastic disease, causing the injected tracer to completely bypass the infiltrated node 1.Beyond colloid particles, the more specific receptor-targeting small molecule [99mTc]Tilmanocept has recently been approved for scintigraphic SLN detection. Tilmanocept, or mannosyl diethylene-triamine-pentaacetate (DTPA) dextran, has a small molecular size of approximately 7 nm and works via specific binding to the mannose receptor (CD206) 2. The mannose receptor is particularly overexpressed on macrophages and dendritic precursor cells within lymph nodes, thus uptake in lymph nodes is not dependent on particle size 2, 3. In pilot studies scintigraphic SLN detection with [99mTc]Tilmanocept was superior to dye staining 4. Given its beneficial properties, [99mTc]Tilmanocept might offer advantages over the alternatively used radiocolloids. We present four cases of [99mTc]Tilmanocept application after inconclusive or unsuccessful attempts of SLN detection using [99mTc]nanocolloid lymphoscintigraphy.

Significance of the preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the future remnant liver: a sequential study of regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the whole liver.

BACKGROUND: The relationship between posthepatectomy complications and liver functional parameters was preliminary reported in a pilot study. The present study sequentially evaluated the clinical significance of maximal removal rate of technetium-99m-galactosyl human serum albumin (GSARmax) in the future remnant liver (rGSARmax) in patients to predict posthepatectomy complications. METHODS: Between 2010 and August 2017, GSARmax, rGSARmax, their difference (Dif), and the rGSARmax to GSARmax ratio were examined in 247 additional patients who underwent hepatectomy for liver and biliary diseases. Hepatectomy-related postoperative complications (i.e. long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 73 (29.6%) patients. RESULTS: The median and mean preoperative GSARmax values were 0.477 and 0.498±0.166 mg/min, respectively; rGSARmax values were 0.341 and 0.366±0.145 mg/min, respectively; Dif values were 0.105 and 0.132±0.111 mg/min, respectively; and the rGSARmax to GSARmax ratio values were 0.774 and 0.746±0.177, respectively. Among these, the GSARmax and rGSARmax values were significantly correlated with the liver functional parameters ICGR15, LHL15, HH15, prothrombin activity, serum hyaluronic acid level, and platelet count (all P<0.01). The rGSARmax values were significantly lower in patients with long-term ascites (P<0.05), and the predictive cutoff values of rGSARmax were 0.290 mg/min; however, the multivariate logistic regression analysis showed that rGSARmax was not independently related to long-term ascites. CONCLUSION: When accompanied by other functional liver reserve parameters, rGSARmax seemed to be an alternative liver functional parameter related to ascites.

Physiological uptake and retention of radiolabeled resveratrol loaded gold nanoparticles (99mTc-Res-AuNP) in colon cancer tissue.

When tagged with a suitable radionuclide, the cancer targeting properties of trans-resveratrol could be utilized to locate cancerous sites in the body using radionuclide imaging technique. However, the polyphenol due to its rapid and extensive metabolism exhibits low bioavailability in vivo. The study was designed to enhance the cancer targeting efficacy of radiolabeled resveratrol using nano-based technology. Technetium-99m labeled resveratrol loaded gold nanoparticles (Res-AuNP) were synthesized, characterized and evaluated for their cancer targeting efficacy in HT29 colon cancer cells and in animal cancer model. Results of various investigations were compared to corresponding results obtained for 99mTc-AuNP and 99mTc-resveratrol. Cancer cell internalization observed for 99mTc-Res-AuNP was significantly higher than that of 99mTc-AuNP and 99mTc-resveratrol. Also, a gradual rise in target to nontarget uptake with time was observed following i.v. administration of 99mTc-Res-AuNP to colon tumor bearing rats, demonstrating better in vivo targeting of colon adenocarcinoma with 99mTc-Res-AuNP when compared to 99mTc-resveratrol.

The role of 99mTc-DTPA retrobulbar SPECT in staging and follow-up of Graves' orbitopathy.

The pathogenesis of Graves' orbitopathy (GO) is not completely understood. Coexistent hyperfunction of the thyroid gland is frequent; however, GO may also coexist with hypo- or euthyrodism. The course of GO is largely independent of thyroid function, although elevated serum TSH is known to negatively interfere with GO course. GO is severe in 10% of the cases; sight threatening complications may also develop. A successful therapy of GO requires the assesment of both the severity and activity of orbital inflammation. Based on relevant studies and our own experiences, the possible management choices are reviewed here. For this purpose, we compare the clinical value of imaging techniques for detecting the activity of the disease. During the last 15 years, we used 99mTc-DTPA retrobulbar SPECT routinely in more than 1400 patients to facilitate the right therapeutic decision. This diagnostic utility simplified management decisions compared to previously applied alternative techniques. We recommended the routine use of 99mTc-DTPA retrobulbar SPECT for the evaluation and follow-up of GO.

Preoperative maximal removal rate of technetium-99m-galactosyl-human serum albumin of the remnant liver is associated with postoperative tumor relapse in hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: Prognosis in patients with hepatocellular carcinoma (HCC) is not only influenced by tumor-related factors but also by the background liver functions. The maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) of the remnant liver (rGSA-Rmax) is a useful candidate for predicting the liver function and clarifying the relationship between the remnant liver functional reserve and tumor-free survival in patients who have undergone hepatectomy. PATIENTS AND METHODS: One hundred and sixty-five patients with HCC who underwent curative hepatectomy were divided into three groups of hepatitis B virus (B-HCC; n=42), hepatitis C virus (C-HCC, n=58), and non-B, non-C (NBNC-HCC, n=65). The relationship between rGSA-Rmax and survival was examined by univariate and multivariate analyses. RESULTS: In the C-HCC group, the albumin, or LHL15, level was significantly lower, and alanine aminotransferase, ICGR15, and the prevalence of grade B liver damage were significantly higher than other two groups (P<0.05). GSA-Rmax or rGSA-Rmax was not different between the three groups. Lower GSA-Rmax and rGSA-Rmax were only significantly associated with lower tumor-free survival in the C-HCC group by the univariate analysis (P<0.05) but not significantly by the multivariate analysis. CONCLUSION: GSA-Rmax and rGSA-Rmax reflect the severity of liver dysfunction and furthermore, the lower rGSA-Rmax is useful as a complementary factor to predict the early HCC recurrence after hepatectomy.

Preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin is correlated with liver functional parameters, but did not predict postoperative morbidity.

BACKGROUND: Recently, posthepatectomy complications have been predicted by advances of new liver functional parameters, and the technetium-99m-galactosyl human serum albumin (GSA) liver scintigraphy has been applied widely for this purpose. We evaluated the clinical significance of the regional maximal removal rate (GSA-Rmax) in patients with various liver diseases as predictors of posthepatectomy complications. PATIENTS AND METHODS: Between 2012 and March 2016, we examined 200 patients who underwent hepatectomy for liver and biliary diseases. The patients' background liver conditions included chronic viral liver diseases in 147 patients, normal liver in 44 patients, and others in nine patients. Hepatectomy-related postoperative complications (i.e. long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 69 (35%) patients. A multivariate logistic analysis was carried out to detect the predictive parameters for complications. RESULTS: The median and mean preoperative GSA-Rmax was 0.420 and 0.448±0.148 mg/min, respectively. The GSA-Rmax was significantly correlated with liver functional parameters of ICGR15, LHL15, HH15, platelet count, prothrombin activity, and serum hyaluronic acid level (P<0.01), and was significantly correlated with postoperative total bilirubin level and C-reactive protein level (P<0.05). With respect to patient outcomes, GSA-Rmax was significantly lower in patients with long-term ascites (P<0.05). The predictive cutoff value for posthepatectomy long-term ascites for GSA-Rmax was 0.421 mg/min. However, the multivariate logistic regression analysis identified that a higher serum hyaluronic acid level and a lower platelet count were significant, independent factors, but not lower GSA-Rmax. CONCLUSION: GSA-Rmax is one of the liver functional parameters and is a complementary parameter to predict postoperative hyperbilirubinemia, inflammatory responses, and ascites when Tc-GSA scintigraphy is performed.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PURPOSE: To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. METHODS: Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). RESULTS: Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. CONCLUSIONS: This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model.

BACKGROUND: The knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles. METHOD: An ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 µm-0.5 µm], [0.25 µm-1 µm] and [1 µm-9 µm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract. Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing. RESULTS: Planar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub-micron to micron The deposited fractions obtained, for thoracic vs. extra-thoracic regions respectively, were 89 ± 4 % vs. 11 ± 4 % for [0.15 µm-0.5 µm], 78 ± 5 % vs. 22 ± 5 % for [0.25 µm-1 µm] and 35 ± 11 % vs.65 ± 11 % for [1 µm-9 µm]. CONCLUSION: Results obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans.

γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206).

γ-Tilmanocept ((99m)Tc-labeled-tilmanocept or [(99m)Tc]-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used that have high expression of the C-type lectin mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by small interfering RNA treatment and was increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR(+) cells (macrophages and/or dendritic cells) in human sentinel lymph node tissues. Together these data provide strong evidence that CD206 is a major binding receptor for γ-tilmanocept. Identification of CD206 as the γ-tilmanocept-binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases.

Delayed renal tissue tracer transit in Tc-99m-DTPA renography correlates with postoperative renal function improvement in UPJO patients.

OBJECTIVE: The aim of the study was to explore the potential parameters for evaluating the improvement in relative renal function (RRF) in patients with unilateral ureteropelvic junction obstruction (UPJO) who underwent surgery. In this regard we observed the RRF expressed as the obstructed kidney's percentage contribution to overall renal function in technetium-99m diethylenetriaminepentaacetic acid (Tc-99m-DTPA) diuretic renography. MATERIALS AND METHODS: Data on 47 patients, who underwent Anderson-Hynes pyeloplasty for diagnosed unilateral UPJO during the period of February 2003 to October 2014, were retrospectively collected. Tc-99m-DTPA diuretic renography was performed on all patients before and after surgery, and no morphological or functional abnormalities were detected on the contralateral kidney. Several parameters, especially renal tissue tracer transit (TTT), the response to furosemide stimulation, and RRF, were evaluated. All data were analyzed with the statistical software SPSS, 17.0, and a value of P less than 0.05 was considered statistically significant. RESULTS: Data on 42 patients were eventually retained for further analysis; five patients were excluded because of indeterminate TTT. All patients showed obstructive response to furosemide stimulation with a preoperative RRF of 41±12%. Postoperative RRF of the obstructed kidneys was 47±11%, significantly higher than the preoperative RRF (P<0.05). Postoperative RRF improvement (absolute increment≥5%) was seen in 18/42 (43%) patients, and 24/42 (57%) of them manifested with postoperative drainage improvement. After surgery, both the RRF increment and the percentage of patients with postoperative RRF improvement in the preoperative delayed TTT group were significantly higher than those in the normal TTT group (12±7 vs. 2±4%, and 81 vs. 19%, respectively; P<0.05), but no significant difference in postoperative drainage improvement was detected between the two groups (56 vs. 54%, P>0.05). None of the other factors, including the preoperative RRF, obstructed kidney location, surgical method, sex, and age, had a significant influence on postoperative RRF improvement (P>0.05). CONCLUSION: Preoperatively delayed TTT of Tc-99m-DTPA diuretic renography was an independent factor that correlated with RRF improvement of unilaterally hydronephrotic kidneys, and might provide valuable information for surgical decisions pertaining to UPJO patients.

Removal of body surface area normalisation improves raw-measured glomerular filtration rate estimation by the Chronic Kidney Disease Epidemiology Collaboration equation and drug dosing in the obese.

BACKGROUND/AIM: We aimed to compared estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), with (mL/min/1.73 m(2) ) and without body surface area (BSA) normalisation (CKD-EPI_noBSA, mL/min) against measured (99m) Technetium - diethylenepentaacetic acid (Tc-DTPA GFR) (mL/min) in 222 individuals, including 80 with malignancy. METHODS: BSA was calculated for each individual using the Du Bois equation. The CKD-EPI and CKD-EPI_noBSA equations were compared with measured Tc-DTPA GFR with respect to bias, proportion within 30% of GFR (P30) and root mean square error for predicting levels of GFR, and concordance in relation to carboplatin dosing. RESULTS: The mean (SD) for BSA and measured GFR for the entire group was 1.99 (0.25) m(2) and 127 (41) mL/min respectively. The P30 for Tc-DTPA GFR was significantly higher with the CKD-EPI_noBSA (80%) than with the CKD-EPI equation (63%, P = 0.0001). In those with body mass index (BMI) > 30 kg/m(2) , the P30 values for the CKD-EPI_noBSA and CKD-EPI were 74% and 42% respectively (P < 0.0001). Carboplatin dosing concordance for the cancer patients using the CKD-EPI and CKD-EPI_noBSA equation was 71% and 56% respectively (P = 0.07). In 78 individuals with BMI > 30 kg/m(2) , concordance in relation to carboplatin dosing using CKD-EPI_noBSA was 65% compared with 26% with the CKD-EPI (P < 0.0001). CONCLUSION: The CKD-EPI without normalisation (CKD-EPI_noBSA) equation was superior to the CKD-EPI equation in estimating raw-measured Tc-DTPA GFR (mL/min).

[Study of heart region of interest setting method in the hepatic functional reserve index of (99m)tc-diethylenetriamine pentaacetic Acid-galactosyl human serum albumin].

In this study we analyzed the influence of region of interest (ROI) selection on the uptake ratio of the liver to the liver plus heart at 15 min (LHL15) during (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy and determined the optimal ROI by evaluating the individual effects of different ROIs in the heart on LHL15. Twenty patients were randomly selected from those who had undergone (99m)Tc-GSA scintigraphy GSA between April 2008 and June 2009. The liver body (L/B) ratio, liver uptake 15 min (LU15), and LHL15 were analyzed and compared among the following ROIs: entire heart, both ventricles, right ventricle, and left ventricle. There were significant differences in the L/B ratio and LU15 values among the different ROIs. However, LHL15 showed a tendency to shift toward a normal value when the size of the ROI was small (only the right or left ventricle), resulting in a lack of distinction between normal and abnormal LHL15 values. Furthermore, setting the entire heart as the ROI was difficult and reproducibility was low. Our results suggest that the use of both ventricles as the ROI provides optimal LHL15 values during (99m)Tc-GSA scintigraphy.