Ultra-long Field-Of-View Positron Emission Tomography for characterization of indeterminate lung nodules: a pilot study exploring opportunities for clinical research

Indeterminate lung nodules (6-15 mm) are frequent findings in patients
undergoing chest Computed Tomography (CT). In the large randomized controlled
Dutch-Belgian lung cancer screening trial NELSON, overall, 9.2% of the screened
participants had an initially indeterminate CT scan. To decrease mortality from
lung cancer, early identification of malignant lesions among the many lung
nodules is crucial. The probability of malignancy depends on size and other
factors. It is difficult to determine whether a nodule is malignant on size
alone. For further differentiation of a lung nodule, usually, repeated chest CT
scanning is performed at 3-6 months up to 2 years to assess nodule growth,
and/or 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) Positron Emission
Tomography (PET)/CT to evaluate metabolic activity. However, repetitive CT
scans are not favoured because of radiation exposure, patient anxiety, and
potential delay in cancer diagnosis. Furthermore, 18F-FDG PET/CT has thus far
insufficient sensitivity for detection and characterization of small (in
particular < 1 cm) lung nodules, meaning that a negative result does not rule
out the presence of cancer, which thus usually requires further follow-up CT
scans. Improvement in work-up of indeterminate lung nodules is urgently needed,
in particular with the expected introduction of lung cancer screening in the
coming years.

Recently, a ground breaking new PET/CT system design was introduced, namely a
long total body PET. This system has a greatly improved geometric coverage
leading to unprecedented 10 times increased sensitivity compared to current
systems. This increased sensitivity can be used to decrease amount of
administered radioactivity and/or scan time. Combined with digital technology
and excellent time of flight performance, this sensitivity can increase further
by a factor of 6.5 (the so-called effective sensitivity). The combination of
high spatial resolution and high sensitivity makes total body PET a very
promising and potentially ideal non-invasive technique for a more accurate
characterization of indeterminate lung nodules without the need to perform
long-time follow-up imaging.
In the Netherlands, the first tota body PET, an ultra-long FOV PET/CT scanner
manufactured by Siemens, the Siemens Vision Quadra PET/CT system (Siemens
Healthineers, Knoxville, TN, USA) will be installed at the UMCG, with expected
implementation in Q3 2021.

In this study, the aim is to derive optimal imaging procedures and to assess
the technical performance of the Vision Quadra PET/CT system concerning its
feasibility to detect indeterminate lung nodules. Furthermore, this study aims
to preliminary explore the sensitivity, specificity, and accuracy of the
characterisation of lung nodules using the Vision Quadra PET/CT.

After enrolment, patients will receive a standard 3 MBq/kg injection of 18F-FDG
and undergo whole-body dynamic PET/CT acquisition at 30-60 min post-injection
(pi), followed by a 10 min whole-body list-mode PET/CT acquisition.
Subsequently, patients will be asked to hold their breath for 15 seconds to
assess the added value of a single fast deep-inspiration breath-hold
acquisition. At 120 min pi a second 10 min whole-body list-mode PET/CT will be
acquired to potentially further differentiate between inflammation and
malignancy.
The list-mode acquisitions can be reprocessed retrospectively with less counts
to produce images representing scans collected with lower activity
administration or shorter scan times (e.g., a 1 min instead of 10 min PET scan
is equivalent to 10% of the injected activity at scan start). Pharmacokinetic,
semi-quantitative (SUVmax and SUVpeak) and subjective qualitative image
analysis will be correlated with pathology (benign or malignant) of the lung
lesion, and results of a previously performed routine-care 18F-FDG PET/CT and
CT chest.

Intravenous injection of radioactive 18F-FDG

Patients will receive a single standard injection of 18F-FDG followed by two
imaging procedures, i.e., two whole-body 18F-FDG PET/CT scans, each preceded by
a low-dose CT for attenuation correction (radiation exposure approximately 1.5
mSv). The PET effective dose using a single injection of 18F-FDG activity is
approximately 4 mSv. In total the effective dose participants will receive is:
4 + 2x1.5 = 7 mSv.