Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.

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.

A different scintigraphic approach to evaluate the glomerular filtration rate / Una técnica gammagráfica diferente para evaluar la tasa de filtración glomerular

Objective: Multiple nuclear medicine techniques for measuring renal glomerular filtration rate (GFR) are available but some of them are not practical in daily routine use and others have some accuracy issues. Hence the aim of the study was to design a new camera-based approach to measure the GFR and to compare our results with other measured GFR (mGFR) and estimated GFRs (eGFRs) derived from available measurements and equations used in daily clinical practice. Material and methods: 34 patients were included in the study. ∼74MBq (2mCi) Technetium 99m diethylene-triamine-pentaacetic acid (99mTc-DTPA) was administered to the patients during 5min. A simple formula based on a dilution principle was used to measure GFR (ScinGFR). Results: Our formula provided similar mGFR results in narrower range as creatinine clearance did and our results correlated well with results derived from other equations. When ScinGFR values were compared to others, there was a significant difference among them (p=0.031) due to difference between the ScinGFR and Cockroft-Gault. When the results of the ScinGFR compared to others without Cockroft-Gault, the difference among them was not significant (p=0.164). Conclusion: A simple formula considering the extracellular fluid volume was used to predict the split and global kidney functions and despite some discrepancies, good correlation among our results and those derived from available formulas was detected (AU)

Objetivo: Existen múltiples técnicas de medicina nuclear disponibles para medir la tasa de filtración glomerular (GFR), aunque algunas de ellas no resultan muy útiles en la rutina diaria, y otras no son muy precisas. Por tanto, el objetivo de este estudio fue diseñar una nueva técnica basada en el uso de una cámara para medir la GFR y comparar nuestros resultados con otras mediciones de GFR (mGFR) y estimaciones de GFR (eGFRs), derivadas de las mediciones disponibles y las ecuaciones utilizadas en la práctica clínica diaria. Material y métodos: Se incluyó en el estudio a 34 pacientes. Se infundió alrededor de 74MBq (2mCi) de 99mTc-ácido dietilen-triamin-pentaacético (99mTc-DTPA) a los pacientes durante 5min. Se utilizó una fórmula simple, basada en un principio de disolución, para medir la GFR (ScinGFR). Resultados: Nuestra fórmula aportó resultados similares de mGFR en el rango más estrecho logrado por la depuración de creatinina, guardando una correlación muy positiva con los resultados derivados de otras ecuaciones. Al comparar los valores de ScinGFR con otros valores, se produjo una diferencia estadísticamente significativa entre ellos (p=0.031), debido a la diferencia entre ScinGFR y Cockroft-Gault. Al comparar los resultados de ScinGFR con otros valores, sin considerar Cockroft-Gault, la diferencia entre ellos fue estadísticamente significativa (p=0.164) Conclusión: Se utilizó una fórmula simple considerando el volumen de líquido extracelular, para predecir las funciones globales e individuales renales y, a pesar de ciertas discrepancias, se detectó una buena correlación entre nuestros resultados y aquellos derivados de las fórmulas disponibles (AU)

Chemical stability of (99m)Tc-DTPA under aerobic and microbially mediated Fe(III)-reducing conditions in porous media.

(99m)Tc-DTPA has been used as a conservative tracer to quantify water transport through porous media. However, more information on the reactivity of this (99m)Tc compound under varying geochemical conditions is desirable to better understand its potential uses. We measured the speciation of Tc following amendment of (99m)Tc-DTPA to batch systems spanning a range of controlled biogeochemical conditions. Our results suggest that (99m)Tc-DTPA is stable under the reducing conditions tested. However, freshly precipitated Al-ferrihydrite may displace Tc(IV) from DTPA in the absence of Fe(III)-reducing conditions.

Optimization via specific fluorescence brightness of a receptor-targeted probe for optical imaging and positron emission tomography of sentinel lymph nodes.

The optical properties of a receptor-targeted probe designed for dual-modality mapping of the sentinel lymph node (SLN) was optimized. Specific fluorescence brightness was used as the design criterion, which was defined as the fluorescence brightness per mole of the contrast agent. Adjusting the molar ratio of the coupling reactants, IRDye 800CW-NHS-ester and tilmanocept, enabled us to control the number of fluorescent molecules attached to each tilmanocept, which was quantified by H1 nuclear magnetic resonance spectroscopy. Quantum yields and molar absorptivities were measured for unconjugated IRDye 800CW and IRDye 800CW-tilmanocept (800CW-tilmanocept) preparations at 0.7, 1.5, 2.3, 2.9, and 3.8 dyes per tilmanocept. Specific fluorescence brightness was calculated by multiplication of the quantum yield by the molar absorptivity and the number of dyes per tilmanocept. It predicted that the preparation with 2.3 dyes per tilmanocept would exhibit the brightest signal, which was confirmed by fluorescence intensity measurements using three optical imaging systems. When radiolabeled with Ga68 and injected into the footpads of mice, the probe identified SLNs by both fluorescence and positron emission tomography (PET) while maintaining high percent extraction by the SLN. These studies demonstrated the feasibility of 800CW-tilmanocept for multimodal SLN mapping via fluorescence and PET-computed tomography imaging.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

Potential dose to nuclear medicine technologists from 99mTc-DTPA aerosol lung studies.

Air sampling performed during 190 Tc-labeled DTPA aerosol lung ventilation studies indicated that the maximum airborne concentration to which the nuclear medicine technologists might be exposed was 7.1 x 10(-1) Bq mL(-1) (1.9 x 10(-5) microCi mL(-1)). If a single technologist performed ALL the aerosol studies, at this maximum airborne concentration, based on the Annual Limit on Intake (ALI), the resulting dose equivalents could be either 1 mSv (100 mrem) to the lungs or 0.1 mSv (10 mrem) to the total body. However, the procedures are shared by the technical staff, the times of exposure are represented by only a fraction of the overall procedure time, and the average airborne concentrations were found to be more than an order of magnitude lower than the maximum. This resulted in a projected average annual dose equivalent of 7.0 x 10(-3) mSv (0.7 mrem) to the lungs or 7.0 x 10(-4) mSv (0.07 mrem) to the whole body from the performance of these procedures.

The use of a modified technique to reduce radioactive air contamination in aerosol lung ventilation imaging.

The aim of this study was to reduce airborne contamination resulting from the use of aerosols in lung ventilation scintigraphy. Lung ventilation imaging is frequently performed with 99mTc-diethylenetriaminepentaacetate aerosol (DTPA), derived from a commercial nebuliser. Airborne contamination is a significant problem with this procedure; it results in exposure of staff to radiation and can reduce gamma camera performance when the ventilation is performed in the camera room. We examined the level of airborne contamination resulting from the standard technique with one of the most popular nebuliser kits and tested a modification which significantly reduced airborne contamination. Air contamination was measured while ventilating 122 patients. The modified technique reduced air contamination by a mean value of 64% (p = 0.028) compared with the standard control technique. Additionally, differences in contamination were examined when a mask or mouthpiece was used as well as differences between operators. A simplified method of monitoring air contamination is presented using a commonly available surface contamination monitor. The index so derived was proportional to air contamination (r = 0.88). The problems and regulations associated with airborne contamination are discussed.

Technetium-99m DTPA aerosol contamination in lung ventilation studies.

UNLABELLED: Contamination of working areas by 99mTc DTPA aerosol is of concern to nuclear medicine technologists. This study sought to determine the extent of 99mTc DTPA contamination to technologists, and to localize sources of aerosol leakage so that methods could be identified that would minimize contamination. METHODS: Fifty to eighty millicuries 99mTc DTPA, diluted to a volume of 4-5 ml with normal saline, were injected into the nebulizing chamber of two commercially available inhalation aerosol systems. The patient's nostrils were clamped and a damp washcloth was wrapped around the patient's mouth. An alcohol swab was placed in the exit port of the exhaust filter in each delivery system, and the technologist involved wore a face mask during the inhalation phase. The patient breathed DTPA-labeled aerosol by mouth until the counting rate in the lungs was four times greater than the counting rate from the pulmonary perfusion phase. Connecting joints of the delivery system were then wipe tested. Last, a Geiger-Mueller detector (pancake probe) was used to survey all device components. Readings above 0.05 mR/hr were considered contaminated. RESULTS: The patient was the greatest source of leakage as determined by the damp washcloth, followed by the joints of the tubes of the delivery system and, finally, the system's exhaust filter. Contamination readings from face masks worn by technical personnel during the lung ventilation studies were slightly greater than 0.05 mR/hr. CONCLUSION: The findings support trace levels of contamination to both the technologist and room while performing 99mTc DTPA aerosol ventilation studies. Comparative data using the two delivery systems revealed little difference in sources of leakage and little variation in contamination measurements.

A comparison of three gastric lavage methods using the radionuclide gastric emptying study.

To determine the percentage of liquid gastric contents experimentally removable by available orogastric lavage systems, five healthy young volunteers were asked to ingest 1 mCi of liquid technicium-99m diethylenetriaminepentaacetic acid (Tc99m-DTPA) mixed with 50 ml tap water. Five minutes afterwards, the radionuclide was lavaged using one of three different techniques-a single syringe method, a closed gravity drainage system, and a closed double syringe method--while continuous radioisotope camera images were taken. Control images, with no lavage performed, were also taken. All of the orogastric lavage methods removed a mean of between 80% and 85% of the stomach contents. The double syringe method was the quickest, while the single syringe method was least tolerated. When compared with control, none of the lavage techniques pushed gastric contents into the duodenum. Thus, in terms of amount of liquid gastric contents removed, there was no one method that removed more than the others. Caution should be exercised in assuming that 80-85% of a liquid gastric ingestion can be removed by lavage in the uncontrolled clinical setting. The use of any orogastric lavage for ingestion evacuation should be undertaken knowing that it is a morbid procedure and usually not necessary.

Radioaerosol 99mTc-DTPA characterization produced by some nebulizers.

1. The radioaerosol 99mTc-DTPA produced by jet and ultrasonic nebulizers was characterized by measuring the median mass diameter (MMD) and geometric standard deviation (sigma g) and these characteristics were interpreted in terms of the aerodynamic principles of inertial impactation. 2. Jet nebulizers of the same model, with different outflows (NSA = 0.14 ml/min; NSB = 0.24 ml/min and NSC = 0.40 ml/min) showed different radioaerosol mass distribution, with MMD (NSC) > MMD (NSA). The ultrasonic nebulizer US-1000 from Narcosul, which is operated with an air flow of 2 l/min and frequency of 1.6 MHz, generated radioaerosol with MMD = 2.40 microns, higher than that obtained with most of the jet nebulizers evaluated (NSA = 1.50 microns; NSB1V = 1.40 microns; NSB2V = 1.20 microns and PITT#1 - 0.80 microns), and the ultrasonic nebulizer presented the highest outflow of the nebulized solution (1.15 ml/min). 3. Connecting one or two impactation reservoirs to the NSB jet nebulizer modified the mass distribution, which became significantly narrower for NSB2V when compared to the other two nebulizers. NSB2V presented a mass percentage with a diameter of 3 microns or less and a sufficient outflow for use in ventilation and pulmonary permeability studies. 4. Comparison of the mass collected in the cascade impactor and the total mass generated by the NSB, NSB1V and NSB2V nebulizers showed, on average, 4.5% efficiency in radioaerosol generation with a diameter of less than 16 microns and 3.2% efficiency for a diameter of 3 microns or less.

Proposal for a compputer program for 99m Tc-DTPA alveolar capillary clearance study

Os radioaerossóis e a cintilografia de ventilaçäo tem papeis bem definidos na rotina medica nuclear. Estudos sobre o clearance alveolo-capilar de tecnécio-99m marcando o ácido dietileno triamino penta-acético (99mTc-DPTA) permitem um diagnóstico precoce, ao menos presuntivo, de infecçöes pulmonares oportunistas, com uma sensibilidade maior que a dos estudos convencionais. Nós desenvolvemos um programa no computador acoplado à câmara de cintilaçäo para processar as imagens adquiridas, resultando em modo rápido e eficiente para quantificaçäo do clearance alveolo-capilar. Realizamos, a título de ilustraçäo, um teste clínico em um voluntário (35 anos, fumante, normal), que nos mostrou ser o programa adequado do ponto de vista de processamento. Adicionalmente, os resultados (pulmäo direito: 2,22 por cento/min; pulmäo esquerdo: 1,86 por cento/min) estäo de acordo com os dados encontrados na literatura