Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Abstract

Purpose: Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume. Procedures: Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 μl, 8-10 weeks old (N=10), (B) 30 μl, 8-10 weeks old (N= 20), and (C) 30 μl, 32 weeks old (N=16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing 18 FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information. Results: Mean±SD (5.69±4.51%) of the solution administered reached the lungs in group A, 41.84±8.03% in group B, and 36.65±16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (PG0.001), but not depending on animal age. Conclusions: In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 μl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.

Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways

“…Although the anatomy below the upper trachea could not be imaged in this nasal airway study it is likely that fluid reached further into the lung airways, a finding consistent with a recent low-resolution radiotracer study. 7 The results also supports our finding that long term gene expression was produced in the lung by a lentiviral vector containing the luciferase transgene that was delivered to the nose and was designed specifically to produce nasal airway gene transfer. 22 It follows that smaller gene vector doses might be able to produce the same levels of gene expression in the anterior nasal airways.…”

“…Small-animal CT, and to a lesser extent MRI, which provide 3-dimensional (3D) information via tomographic approaches, could be used to examine murine airways but the time to acquire 3D data sets prohibits tracking of high speed dynamic events such as fluid dosing at high spatial resolutions. Although PET-CT has been used to show the final location of trans-nasally delivered solutions 7 , the acquisition speed and spatial resolution of PET is very low, the dynamics of the fluid delivery cannot be imaged, the air containing spaces are poorly defined by CT and the spatial resolution is insufficient. None of these methods can visualize fluid movement in mouse airways at high resolution.…”

Intubation-mediated Intratracheal (IMIT) Instillation: A Noninvasive, Lung-specific Delivery System

“…As discussed above, intranasal delivery of compounds into mice results in a low efficiency, highly variable delivery of reagents into the target organ of the lung. Intranasal delivery of Positron Emission Tomography (PET) imaging reagents to the murine lung yielded a 40% delivery efficiency 11 , whereas we have demonstrated that IMIT offers an excellent alternative to other lung delivery approaches with its >98% delivery efficacy and multilobar distribution. This improvement in targeted delivery to the lung has the potential to increase the reproducibility of therapeutic delivery for treatment of pulmonary disease.…”

Impact on allergic immune response after treatment with vitamin A

“…Groups of mice were immunized by intraperitoneal injections of 5-μg Dermatophagoydes pteronyssinus (HDM, Alk-Abelló, Spain) complexed with 2-mg aluminum potassium sulphate (Alum, Sigma Chemical Co., St Louis, Mo) on days 0 (D0) and 4 (D4). On D14 and D15, mice were challenged with 5-μg HDM delivered intranasally [ 21 ] after slight anesthesia. Additional experiments were performed with chicken egg albumin (OVA, Sigma) plus Alum as described previously [ 22 ].…”