European Nuclear Medicine Guide
99mTc-nanocolloids
Functioning respiratory cilia are the basis for normal mucociliary clearance (MC) [11]. Through the trapping of inhaled particulate matter and coordinated motility of the cilia to the oropharynx followed by swallowing, this mechanism acts as a mechanical barrier.
This process can be investigated by measuring the speed of MC in the nose (NMC) by following the movement of a 99mTc-nanocolloid droplet across the nasal mucosa in the direction of the pharynx for a specific duration of time 1 [2]. The speed of movement of the radioactive droplet is calculated by measuring the displacement of radioactivity, corrected for small head movements.
The investigation of MC can also be performed by means of inhalation of radioactive aerosols and measuring the pulmonary radioaerosol MC (PRMC) up through the bronchial airways [13, 14]. This transport can be quantified as e.g. % clearance per hour from the lungs and compared to reference values. In the trachea, the normal speed of radioactive boluses (tracheobronchial velocity, TBV) is ~4 (range 2–6) mm/min in healthy non-smoking adults [13, 14]. The PRMC technique may also be used to measure efficacy of coughing by measuring cough clearance [11,13,14].
Assessment of nasal mucosa function in recurrent upper respiratory tract infections, pre- and post-surgery;
Preliminary screening prior to biopsy in suspected primary ciliary dyskinesia (PCD, ~Kartagener syndrome);
Suspicion of secondary ciliary dyskinesia caused by mechanical factors such as bronchoscopy, endotracheal intubation, surgery, persistent cough, radiotherapy (dose >2 Gy), chemical factors such as prolonged exposure to cigarette smoke, severe air pollution, (intranasally administered) drugs or stimulants, inflammatory/bacterial causes, or anatomical changes such as tracheobronchial malacia or fistula;
Assessment of mucociliary and/or cough clearance in connection with pharmacological or physical intervention.
Nasal congestion at the time of the investigation should be a reason to consider rescheduling of NMC testing.
NMC and PRMC testing should be postponed to 3–6 weeks after resolution of an acute airway infection.
Apart from smoking, aging, and asthma/COPD, mucociliary clearance is decreased in cases of abnormal hyperviscous mucus (e.g. cystic fibrosis), abnormal ciliary ultrastructure (e.g. PCD, a group of rare usually autosomal recessive diseases), and a wide range of chemical, mechanical, and inflammatory mediators [11]. This test assesses the functioning of the mucociliary transport mechanism in the nose or the lower airways. The nasal test is similar to the saccharin test, in which a saccharin particle is placed in the nasal cavity and the time to tasting saccharine is noted. The latter test clearly requires extensive patient cooperation. The nuclear medicine test is more objective, and even more so if measured with radioaerosols in the lower airways [12-14].
PRMC can be performed from the age of 5 years, has a high rate of conclusive test (90%), and a specificity of nearly 100% [13, 14] for excluding a PCD diagnosis [13]. However, if absent mucociliary transport is measured in a patient suspected of having PCD, work-up can be supplemented by different tests such as measurement of nasal nitric oxide, where a low value points towards PCD; electron microscopic examination of the ultrastructure of the cilia, video microscopy of ciliary beat pattern and frequency, and genetic testing [14]. Genetic testing is developing rapidly and about 50 PCD disease-causing genes are known, so around 70% of patients can be diagnosed this way.
The suggested activity to administer is 2 MBq deposited on the nasal floor, or 2–10 MBq to the lower airways.
No recommendations are available for paediatric nuclear medicine, but the methods are also used in the work-up of children [12,13,14].
The effective dose per inhaled activity is 4.9 µSv/MBq [13].
The effective dose for an inhalation of 40 MBq is 0.2 mSv.
The administered activity is 2 MBq, deposited on the nasal floor. The effective dose ranges from 48 µSv (70 kg adult) to 152 µSv (5-year-old). The ED for an inhalation of 10 MBq to the lungs is 0.05 mSv.
Caveat
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
Healthy non-smokers have an average nasal mucociliary transport speed of 6 mm/min, with a range of 2–12 mm/min. It should be emphasized that this test has a good sensitivity (up to 100%). In PCD, little or no mucociliary transport is measured in either nostril (average 0.2 mm/min, range 0–0.7 mm/min), provided the patient has been properly instructed and has not sniffed during the investigation. However, the specificity of this test is low (approximately 55%). Numerous disorders can ultimately result in greatly reduced or absent mucociliary transport (drug use, viral/bacterial infections, or anatomical abnormalities) [11].
If there is no transport of the activity, consider repeating the test 1 to 2 weeks later while any local drugs are stopped. If the outcome of the test remains the same, this is considered definitive.
At least 2 days beforehand, the patient should not use any local drugs, particularly decongestants, that can influence the function of the ciliary epithelium.
Sympathomimetic drugs must be avoided. Local corticosteroid sprays may continue to be used. If a local sympathomimetic drug such as oxymetazoline is used chronically (>14 days in a row), it must be stopped 14 days prior to the NMC test to allow the rebound swelling of the nasal mucosa to recover.
No EANM guidelines are available at this time.
Confirm that any drugs that could affect the results of the investigation have been adequately suspended and that the patient has had no recent airway infection.
For NMC testing, one method can be summarised as follows [12]: Tell the patient, prior to drawing up the active droplet, to breathe through their mouth during the imaging and not to sniff before or during the investigation. Especially with children, it is worthwhile showing the pipette beforehand, since once fixed to the camera, the sight of it might cause distress accompanied by tears and sniffing, potentially rendering the investigation inconclusive.
Using tape, fix a point source to the tip of the nose and to the mastoid (behind the ear at the level of the meatus) or in front of the tragus in order to correct for movement but also act as an anatomical reference. The patient sits with the head left or right laterally against the gamma camera, and the head is fixed in position, preferably with a head support (e.g. a vacuum sac or modified eye measurement head support). The patient is positioned in such a way that the reference markers are aligned horizontally. Spread the naris using the nasal speculum and inspect the nasal cavity. Using the pipette, a droplet of [99mTc]Tc-nanocolloid is deposited on the nasal floor, 1cm behind the frontal section of the concha inferior (inferior turbinate) or naris.
Dynamically acquire 20(–40) frames of 30 sec in a 128x128 (64x64) matrix for 10–20 min.
To calculate the transport speed, the pixel size of the gamma camera used must be known. The displacement of the maximum counts of the deposit is measured in pixels/minute and corrected for movement of the head. Head movement is inferred from the displacement of the maximum number of counts of the point sources on the tip of the nose and mastoid. The transport speed is expressed in mm/min.
It is possible to repeat the investigation for the other nostril if no nasal mucociliary transport is observed; before doing so, ask the patient to blow his or her nose thoroughly to remove remnant radioactivity.
For PRMC testing, one method can be summarised as follows [13,14]: First, a radioaerosol is inhaled with repeated e.g. 20(–40) slow inhalations and forced expirations. Static and dynamic gamma camera imaging is then performed for the next two hours, with a final image taken after 24 hours. Retention (or clearance) at different timepoints is compared to the expected, based on reference values that depend on the initial radioaerosol distribution in the lungs (penetration index) and the sex and age of the subject. In addition, TBV (in mm/min) is measured from the dynamic images, and cough clearance can also be assessed [13,14].