Pulmonary Recurrence of Colorectal Mucinous Adenocarcinoma and Sarcoidosis on 18 F-FDG PET/CT.

ABSTRACT: A 67-year-old woman, previously diagnosed with pulmonary sarcoidosis and sigmoid colon mucinous adenocarcinoma with pulmonary metastasis, showed an enlarged pulmonary nodule in routine follow-up. Because of the absence of treatment for either condition over the past 3 years, the nodule raised concerns of cancer recurrence or sarcoidosis progression. Its distinctive 18 F-FDG PET/CT appearance, compared with other pulmonary lesions, suggested a mucinous histology. The diagnosis was confirmed by pathological examination. This emphasizes the importance of knowledge of the 18 F-FDG PET/CT phenotype of neoplastic histological variants to address challenging diagnostic scenarios.

Impact of gas humidification and nebulizer position under invasive ventilation: preclinical comparative study of regional aerosol deposition.

Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 cm to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99mtechnetium-labeled diethylene-triamine-penta-acetic acid. Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions are more likely to cause peripheral deposition of aerosols in the lungs. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification.

Brown tumors in nuclear medicine: a systematic review.

Brown tumors (BT) are abnormal bone-repair processes and a consequence of hyperparathyroidism. The diagnosis of these lytic lesions in nuclear medicine, while a challenge, is not so rare, because functional imaging is used both in the management of cancer and hyperparathyroidism. The main objective of this review is to summarize the knowledge and the evidence concerning BT and the different imaging modalities in nuclear medicine. A systematic review was performed in Embase, PubMed and Google Scholar from 2005 to 2022. We included articles describing BT in the following imaging modalities: [18F]-fluorodeoxyglucose PET/CT, [18F]-fluorocholine or [11C]-fluorocholine PET/CT, [99mTc]-Sestamibi scintigraphy, bone scan, [18F]-sodium fluoride PET/CT, [68Ga]-FAPI PET/CT; [68Ga]-DOTATATE PET/CT; [11C]-methionine PET/CT. For each modality, appearance, avidity for radiotracer, available quantitative parameters and imaging evolution after parathyroidectomy were collected and analyzed. Fifty-two articles were included for a total of 392 BT lesions. If the diagnosis of BT is evoked on a known lesion, performing a [18F]-fluorocholine PET/CT imaging seems the most appropriate. In [18F]-fluorodeoxyglucose, [18F]-fluorocholine, [18F]-sodium fluoride PET/CT and bone scan, BT can mimic metastatic disease. BT uptakes appear reversible after parathyroidectomy, with a more or less rapid decrease depending on the imaging modality used.

Technical features of vaping drug delivery system for bronchodilator delivery.

PURPOSE: Several technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). METHODS: Terbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). RESULTS: GS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. CONCLUSION: We proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

Therapeutic optimization in head and neck radiotherapy planning: Advocacy for 18FDG PET-CT in treatment condition.

INTRODUCTION: The necessity to perform 18FDG PET-CT both for initial tumour staging and for target volume delineation in head and neck cancers seems well established. The aim of the present study is to advocate the place and role of 18FDG PET-CT acquired in planning treatment position (18FDG PET-CT/RT). METHODS: Between March 2018 and July 2019, 22 patients with a squamous cell head and neck carcinoma treated by EBRT were included in the analysis. All these consecutive patients had a 18FDG PET-CT/RT. Three GTV volumes were defined. First, "GTV 40%" corresponded to 40% of SUVmax. "Visual GTV" was defined as the tumor volume obtained from the PET the nuclear medicine physician interpreted. The radiation oncologist used the medical record, clinical anatomy, CT simulation and 18FDG PET-CT/RT data ("GTV40%" and "visual GTV") to draw the GTV. RESULTS: Mean GTVs and mean "GTVs40%" were significantly different (P<0.001) with an intraclass index of 0.734. Mean "GTV40%" and mean "visual GTVs" were also significantly different (P<0.001) with an intraclass index of 0.72. Conversely, the difference between mean GTVs and mean "visual GTVs" were not significant (P=0.11) with an intraclass index of 0.91. Mean DICE between "GTVs40%" and GTV was 0.7 (ranging from 0.2 to 0.9). The mean intersection between GTVs and "visual GTVs" volumes was 0.8 (ranging from 0.4 to 1). The difference between DICES was significant (P=0.015), "visual GTV"/GTV DICE was the smallest. CONCLUSION: 18FDG PET-CT/RT definitely remains the imaging modality that individualized/customized head and neck cancer treatment needs.

Performance of quantitative measurements in [18F]fluorocholine positron emission tomography/computed tomography for parathyroid imaging (P2TH study).

Objective: [18F]Fluorocholine positron emission tomography/computed tomography (PET/CT) is used frequently in addition to [99mTc]Tc-Sestamibi scintigraphy and ultrasonography for the location of hyperfunctioning parathyroid glands. The aim of this study is to evaluate the performance of quantitative criteria in [18F]fluorocholine PET/CT for localization of hyperfunctioning parathyroid glands. The secondary objective is to highlight a correlation between the detection rate of [18F]fluorocholine PET/CT and serum parathyroid hormone (PTH) level. Materials and methods: In two academic centers, we retrospectively included patients with biological hyperparathyroidism (HPT) and who had [18F]fluorocholine PET/CT. After a visual analysis, to measure the overall performance of [18F]fluorocholine PET/CT, a blind reading was carried out with standardized measurements of maximum standardized uptake value (SUVmax), liver ratio, thyroid ratio, and size ratio. We analyzed the quantitative criteria of [18F]fluorocholine PET/CT compared to the histological results, in particular to identify differences between adenomas and hyperplasias. We compared the performance of each quantitative criterion to the overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]fluorocholine PET/CT. The detection rate of hyperfunctioning parathyroid glands was calculated in subgroups of serum PTH level. Results: The quantitative criteria in [18F]fluorocholine PET/CT were measured for 120 patients (135 lesions). The areas under the receiver operating characteristic (ROC) curve representing SUVmax and liver ratio were significantly increased. The optimal cut-off values represented by the maximum Youden index was >4.12 for SUVmax and >27.4 for liver ratio. Beyond certain threshold values of SUVmax (>4.12) or liver ratio (>38.1), all the lesions were histologically proven adenomas. SUVmax and liver ratio were significantly higher for adenomas than for hyperplasias and differential diagnosis (p = 0.0085 and p = 0.0002). The positivity of [18F]fluorocholine PET/CT was correlated with PTH level. Detection rates were 55.56, 75.56, and 87.5%, respectively, for serum PTH < 70, 70 to 120, and >120 ng/ml. Conclusion: Semi-quantitative measurements (SUVmax and liver ratio) should be considered as additional tools in interpretation of [18F]fluorocholine PET/CT. These quantitative parameters have lower overall performance but higher specificity than overall visual analysis in identifying an adenoma. Above certain threshold values, all lesions are adenomas. [18F]fluorocholine PET/CT confirms excellent performance for the detection of hyperfunctional parathyroids. For serum PTH levels < 70 ng/ml, the detection rate of [18F]fluorocholine PET/CT is strongly decreased.

Diplopia Related to a Pediatric Cervical Rhabdoid Tumor in 18 F-FDG PET.

ABSTRACT: Increased muscle uptake is commonly seen with 18 F-FDG PET/CT because of an important physiological muscle glucose metabolism. Muscle uptake can express a recent significant muscle activity. However, the absence of muscle uptake is almost never described or interpreted. We describe the case of an 8-year-old boy with extrarenal rhabdoid tumor in the right carotid space. An MRI and an 18 F-FDG PET/CT were performed for the diagnostic workup. There was no uptake in the lateral rectus oculomotor muscle unlike all other oculomotor muscles. The ophthalmological examination found a diplopia confirmed by the Lancaster test.

Assessment of High-Power Electronic Nicotine Delivery System as an Alternative Aerosol Device for Terbutaline Delivery.

PURPOSE: The performance of new-generation high-power electronic nicotine delivery system (ENDS) for the administration of inhaled terbutaline was assessed. METHODS: The formulation of e-liquid was carried out using terbutaline in combination with 1, 3- propanediol. Several terbutaline concentrations (from 0.3125 to 2.500 mg / mL) and power levels (from 15 to 35 W) were assessed using a box type ENDS. The respirable drug dose was determined using a Glass Twin Impinger and quantified by liquid chromatography coupled with a UV-detector. The Next Generation Impactor and the Dekati Low Pressure Impactor were used to measure the aerosol particle size distribution in drug mass. The results were compared with a jet nebulizer (Cirrus TM 2) similar to the usual clinical conditions (2 mL at [terbutaline] of 2.5 mg / mL). RESULTS: The optimal conditions to maximize terbutaline delivery using ENDS are a drug concentration at 1 mg/mL, and a power level at 30 W, to reach a respirable dose of 8.73 ± 0.90 µg/puff. By contrast, during a 5 min nebulization, the respirable dose of terbutaline was 1040 ± 33 µg whatever the cascade impactors and the aerosol devices used. The mass median aerodynamic diameter (MMAD) remains similar for jet nebulizer and ENDS in the 1.74-2.07 µm range. CONCLUSION: Compared to the jet nebulizer, a same respirable dose of terbutaline at the same range of aerosol size distribution was delivered by ENDS if 120 puffs were performed. The ENDS can be considered as an alternative aerosol device for terbutaline delivery.

Outcome Prediction at Patient Level Derived from Pre-Treatment 18F-FDG PET Due to Machine Learning in Metastatic Melanoma Treated with Anti-PD1 Treatment.

(1) Background: As outcome of patients with metastatic melanoma treated with anti-PD1 immunotherapy can vary in success, predictors are needed. We aimed to predict at the patients' levels, overall survival (OS) and progression-free survival (PFS) after one year of immunotherapy, based on their pre-treatment 18F-FDG PET; (2) Methods: Fifty-six metastatic melanoma patients-without prior systemic treatment-were retrospectively included. Forty-five 18F-FDG PET-based radiomic features were computed and the top five features associated with the patient's outcome were selected. The analyzed machine learning classifiers were random forest (RF), neural network, naive Bayes, logistic regression and support vector machine. The receiver operating characteristic curve was used to compare model performances, which were validated by cross-validation; (3) Results: The RF model obtained the best performance after validation to predict OS and PFS and presented AUC, sensitivities and specificities (IC95%) of 0.87 ± 0.1, 0.79 ± 0.11 and 0.95 ± 0.06 for OS and 0.9 ± 0.07, 0.88 ± 0.09 and 0.91 ± 0.08 for PFS, respectively. (4) Conclusion: A RF classifier, based on pretreatment 18F-FDG PET radiomic features may be useful for predicting the survival status for melanoma patients, after one year of a first line systemic treatment by immunotherapy.

Using 99mTc-(V)-DMSA to follow the vascular calcification process in vascular smooth muscle cells based on pit-1 expression.

BACKGROUND: Vascular calcification is an established feature of atherosclerosis process. The sodium/phosphate transporter PiT-1 acts as a biosensor in vascular calcification of VSMCs. [99mTc]-Pentavalent dimercaptosuccinic acid (99mTc-(V)-DMSA) was mediated by PiT-1 transporter in tumoral cells and we propose its evaluation in a vascular calcification in vitro model. The aim of this study was to determine if 99mTc-(V)-DMSA can follow the vascular calcification process in vascular smooth muscle cells (VSMCs) based on PiT-1 expression. METHODS: From a rat aortic VSMC cell line (A7r5), we set up a model of calcification within 7 days using a calcifying medium containing a high inorganic phosphate concentration. Phosphocalcic deposits were monitored with Alizarin red and Von Kossa staining and with phase contrast microscopy. PiT-1 expression was evaluated with an immunofluorescence assay and osteopontin expression, with whole cell ELISA assay. 99mTc-(V)-DMSA uptake was measured in control and calcifying conditions and compared with optical microscopy evaluation. RESULTS: Under hyperphosphatemia conditions, the VSMC cells progressively overexpressed osteopontin protein, PiT-1 transporter, and synthetized mineralized matrix with phosphocalcic deposition. 99mTc-(V)-DMSA uptake was to 2.8±2.08%DA/mg-protein in control cells and 42±24%DA/mg-protein in calcified cells (P<0.001). PiT-1 inhibition with phosphonoformic acid completely reverse the calcium deposition as well as the 99mTc-(V)-DMSA uptake. These results demonstrated that 99mTc-(V)-DMSA in-vitro uptake is mediated by PiT-1 transporter and follow the VSMC calcification process. CONCLUSIONS: These preliminary in-vitro results showed 99mTc-(V)-DMSA uptake follow the phospho-calcic deposition mediated by PiT-1 transporter. This radiotracer may have some potential to detect changes of VSMC metabolism occurring in the atherosclerosis process.

Utility of 18F-FDG PET/CT in medical care of a promyelocytic sarcoma.

Promyelocytic sarcoma is an uncommon solid tumor made up of myeloblasts. It is characterized, like acute promyelocytic leukemia (APL), by a chromosomal translocation t(15;17) involving the retinoic acid receptor alpha (RARalpha) and the promyelocytic gene (PML). The diagnosis and monitoring of promyelocytic sarcoma is a challenge due to the rarity and severity of the disease. We describe a case with several initial sites and without APL. The patient was monitored with regular 18F-FDG PET/CT from diagnosis to complete response. The evolution of PET/CT imageries was compared to the quantification of PML-RARα fusion gene by RQ-PCR. In promyelocytic sarcoma medical care, 18F-FDG PET/CT appears to be an attractive tool for finding targets for biopsy, for the primary staging, for assessing therapeutic response and for detecting early relapse.

Positron emission tomography for radiotherapy planning in head and neck cancer: What impact?

PET-computed tomography (CT) plays a growing role to guide target volume delineation for head and neck cancer in radiation oncology. Pretherapeutic [18F]FDG PET-CT adds information to morphological imaging. First, as a whole-body imaging modality, it reveals regional or distant metastases that induce major therapeutic changes in more than 10% of the cases. Moreover, it allows better pathological lymph node selection which improves overall regional control and overall survival. Second, locally, it allows us to define the metabolic tumoral volume, which is a reliable prognostic feature for survival outcome. [18F]FDG PET-CT-based gross tumor volume (GTV) is on average significantly smaller than GTV based on CT. Nevertheless, the overlap is incomplete and more evaluation of composite GTV based on PET and GTV based on CT are needed. However, in clinical practice, the study showed that using GTV PET alone for treatment planning was similar to using GTVCT for local control and dose distribution was better as a dose to organs at risk significantly decreased. In addition to FDG, pretherapeutic PET could give access to different biological tumoral volumes - thanks to different tracers - guiding heterogeneous dose delivery (dose painting concept) to resistant subvolumes. During radiotherapy treatment, follow-up [18F]FDG PET-CT revealed an earlier and more important diminution of GTV than other imaging modality. It may be a valuable support for adaptative radiotherapy as a new treatment plan with a significant impact on dose distribution became possible. Finally, additional studies are required to prospectively validate long-term outcomes and lower toxicity resulting from the use of PET-CT in treatment planning.

Incidental Detection of a Small Cell Lung Cancer by 18F-Choline PET/CT Performed for Recurrent Hyperparathyroidism After Parathyroidectomy.

ABSTRACT: We report the case of a 64-year-old woman with musculoskeletal pain and elevated serum parathyroid hormone who had undergone parathyroidectomy for primary hyperparathyroidism 4 years earlier. An 18F-choline PET/CT scan was performed and incidentally showed an intense uptake in a right upper lobe pulmonary nodule and in the right hilar, mediastinal, and cervical lymph nodes. Histopathological analysis confirmed the diagnosis of a small cell lung cancer. Clinical symptoms and recurrent hyperparathyroidism were therefore consistent with a paraneoplastic syndrome. A complete metabolic response was achieved on 18F-FDG PET/CT scan after chemotherapy.

Incidental Finding of COVID-19 Lung Infection in 18F-FDG PET/CT: What Should We Do?

We report the case of an asymptomatic (no fever, no cough, no dyspnea) 80-year-old woman who had an F-FDG PET/CT scan for initial staging of Lieberkühnian adenocarcinoma located on anal canal. Chest analysis incidentally revealed bilateral diffuse patchy ground-glass opacity with mild increasing F-FDG uptake, consistent with incidental COVID-19 infection finding during the March 2020 pandemic. The infection was confirmed by reverse transcription-polymerase chain reaction. It led us to improve patient flow and to undertake broader measures to avoid patient clinical issues and potential disease spreading.

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.

Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies.

Ethical restrictions are limitations of in vivo inhalation studies, on humans and animal models. Thus, in vitro or ex vivo anatomical models offer an interesting alternative if limitations are clearly identified and if extrapolation to human is made with caution. This work aimed to develop an ex vivo infant-like respiratory model of bronchopulmonary dysplasia easy to use, reliable and relevant compared to in vivo infant data. This model is composed of a 3D-printed head connected to a sealed enclosure containing a leporine thorax. Physiological data and pleural-mimicking depressions were measured for chosen respiratory rates. Homogeneity of ventilation was assessed by 81mkrypton scintigraphies. Regional radioaerosol deposition was quantified with 99mtechnetium-diethylene triamine pentaacetic acid after jet nebulization. Tidal volumes values are ranged from 33.16 ± 7.37 to 37.44 ± 7.43 mL and compliance values from 1.78 ± 0.65 to 1.85 ± 0.99 mL/cmH2O. Ventilation scintigraphies showed a homogenous ventilation with asymmetric repartition: 56.94% ± 9.4% in right lung and 42.83% ± 9.36 in left lung. Regional aerosol deposition in lungs exerted 2.60% ± 2.24% of initial load of radioactivity. To conclude the anatomical model satisfactorily mimic a 3-months old BPD-suffering bronchopulmonary dysplasia and can be an interesting tool for aerosol regional deposition studies.

18F-FDG PET/CT in Urachal Abscess.

We report interesting images of a pelvic mass in an 11-year-old girl. She presented with fever, chronic fatigue, and weight loss without abdominal pain. Abdominal ultrasound, contrast-enhanced CT, and F-FDG PET/CT were equivocal. F-FDG PET/CT revealed an irregular, intense FDG-avid pelvic mass in close contact with the bladder. Both infectious and malignancy complications were suspected, but pathological examination confirmed a urachal abscess. As most of the urachal carcinomas are mucinous adenocarcinomas with low or non-FDG uptake, intense uptake might indicate an abscess rather than a carcinoma.

Umbelliferone Decreases Intracellular pH and Sensitizes Melanoma Cell Line A375 to Dacarbazin. Comparison with Acetazolamide.

BACKGROUND AND OBJECTIVE: The high degree of malignancy of tumour cells is linked to alterations of many physiological parameters like the intracellular pH (pHi). The pHi in cancer cell line is regulated by the carbonic anhydrase IX (CA IX). The main enzymatic function of the CA IX protein is to catalyze the hydration of carbon dioxide into bicarbonate ions and protons. CA IX expression in a broad variety of human tumor tissues is associated with resistance to therapy. One promising approach is to target the mechanism regulating pH homeostasis with carbonic anhydrase inhibitors like sulfamides and coumarins families. METHODS: In this work we have evaluated effects of umbelliferone and acetazolamide in a high resistant melanoma cell line (A375) over expressing CA IX. Impact of effective doses of CA IX inhibitors on apoptosis, intracellular pH (pHi), CA IX protein expression and functionality have been investigated. Determination of effective doses of CA IX inhibitors was performed with MTT tests. We also evaluated sensitization effect of CA inhibitors to conventional therapy as dacarbazin. RESULTS: We have used 10 µM Umbelliferone and 100 µM Acetazolamide as effective doses for 24h. These doses did not induce any apoptosis. Umbelliferone induced a more important pHi decrease than Acetalozamide from 7.3 to 7.08 and to 7.12 respectively, and a more important decrease in s-CA IX fraction showing a decrease in CA IX function. We have demonstrated that pre-treatment with umbelliferone or acetazolamide allows a better dacarbazin efficacy. CONCLUSION: We have demonstrated that inhibitors modify intracellular pH and CAIX functionality and sensitize cells to Dacarbazin. These original results complete the knowledge on Sulfamide CA IX inhibitors, bring new insights about Coumarin compounds and offer new possibilities in high grade melanoma therapies.

Nicotine delivery from the refill liquid to the aerosol via high-power e-cigarette device.

To offer an enhanced and well-controlled nicotine delivery from the refill liquid to the aerosol is a key point to adequately satisfy nicotine cravings using electronic nicotine delivery systems (ENDS). A recent high-power ENDS, exhibiting higher aerosol nicotine delivery than older technologies, was used. The particle size distribution was measured using a cascade impactor. The effects of the refill liquid composition on the nicotine content of each size-fraction in the submicron range were investigated. Nicotine was quantified by liquid chromatography coupled with tandem mass spectrometry. Particle size distribution of the airborne refill liquid and the aerosol nicotine demonstrated that the nicotine is equally distributed in droplets regardless of their size. Results also proved that the nicotine concentration in aerosol was significantly lower compared to un-puffed refill liquid. A part of the nicotine may be left in the ENDS upon depletion, and consequently a portion of the nicotine may not be transferred to the user. Thus, new generation high-power ENDS associated with propylene glycol/vegetable glycerin (PG/VG) based solvent were very efficient to generate carrier-droplets containing nicotine molecules with a constant concentration. Findings highlighted that a portion of the nicotine in the refill liquid may not be transferred to the user.

Assessment of new-generation high-power electronic nicotine delivery system as thermal aerosol generation device for inhaled bronchodilators.

PURPOSE: A need remains for alternative devices for aerosol drug delivery that are low cost, convenient and easy to use for the patient, but also capable of producing small-sized aerosol particles. This study investigated the potential of recent high power electronic nicotine delivery systems (ENDS) as aerosol generation devices for inhaled bronchodilators. METHODS: The particle size distribution was measured using a cascade impactor. The delivery of terbutaline sulfate, a current bronchodilator used for asthma or COPD therapy by inhalation, was studied. This drug was quantified by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The particle size distribution in terms of mass frequency (in two ways, gravimetrically and quantitatively through drug assay on each stage) and the terbutaline sulfate concentration in the aerosol were elucidated. The mass median aerodynamic diameter (MMAD) and the drug delivery rose when the power level increased, to reach 5.6±0.4µg/puff with a MMAD of 0.78±0.03µm at 25W. CONCLUSION: New generation high-power ENDS are very efficient to generate carrier-droplets in the submicron range containing drug molecules with a constant drug concentration whatever the size-fractions. ENDS appear to be highly patient-adaptive.