Test-retest reproducibility of whole body [18F]FDG PET-CT in patients with malignant lung lesions.

Positron emission tomography (PET) is a non-invasive imaging technique based on
the use of biologically relevant compounds labelled with short-lived
positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and
fluorine-18.

With the introduction of hybrid machines, combining PET and computed tomograpgy
(PET-CT), and in the near future PET and magnetic resonance imaging (PET-MRI),
it is possible to evaluate integrated metabolic and anatomic images. This has a
high impact in diagnosing cancer and evaluating response to therapy.

To detect changes in multiple [18F]FDG PET-CT scans in one patient, test-retest
variability needs to be determined, to know when an observed difference is due
to a true biological effect. For response evaluation, PET Response Criteria in
Solid Tumors (PERCIST) have been published with a suggested threshold of 30%
decline in SUV for partial response, and 30% increase for progressive disease
[J Nucl Med. 2009 May;50 Suppl 1:122S-50S.]. These thresholds are based on
performed test-retest studies with different types of cancers and different
scanner acquisitions and types (mainly PET alone).

Repeatability of SUV measurements have been evaluated in advanced
gastrointestinal malignancies by Velasquez et.al [J Nucl Med. 2009
Oct;50(10):1646-54] resulting in a threshold of 34% decrease and 52% increase
for determining true metabolic changes.
In non small-cell lung cancer (NSCLC) test retest reproducibility has been
tested by Hoekstra et.al. [J Nucl Med. 2002 Oct;43(10):1304-9] with a dynamic
[18F]FDG PET only scan. This study showed an intraclass correlation coefficient
of 0.95 for full kinetic analysis (nonlinear regression (NLR)).
Nahmias et.al. [J Nucl Med. 2008 Nov;49(11):1804-8] published the results of a
test-retest study with a variety of cancer types (including NSCLC) with whole
body [18F]FDG PET-CT, with a threshold of an absolute decrease of 0.5 in SUV
mean for response evaluation. In addition to the test-retest repeatability, the
interaction of the (newer) anticancer drugs with the tracer pharmacokinetics
should be taking into account for evaluating response to treatment in the
future. Reproducibility of multiple lesions and including metabolic volume in
the analysis has never been performed to our knowledge.

To date the optimal tracer uptake time is still matter of debate (60 versus 90
min p.i.). Moreover, test-retest (TRT) data is primarily based on (outdated)
PET technology and assessment of TRT for state of the art PET/CT systems is
limited. Finally, several new and extra PET/CT based quantitative tracer uptake
measures have been developed in our institute and are becoming more widely
available, such as SUV based on several new PET based delineation methods [J
Nucl Med. 2011 Oct;52(10):1550-8.], total lesion glycolysis, metabolic volume
[J Nucl Med. 2010 Dec;51(12):1870-7.] and tracer uptake heterogeneity
assessment [Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1636-47]. Yet, there is
no or very limited data on the TRT performance of these new and upcoming
metrics. The purpose of the study is to collect TRT FDG PET images using
current state of the art PET-CT technology to allow for the assessment of TRT
performance of several new quantitative tracer uptake measures that became
feasible for clinical use that have emerged through the development of PET-CT
technology.

To our knowledge no study has been published evaluating the reproducibility of
whole body [18F]FDG PET-CT for malignant lung lesions with two time intervals
(60 and 90 min) postinjection to evaluate test-retest reproducibility of a wide
variety of quantitative tracer uptake measures and to determine the best
time-interval for scanning post-injection.

To detect changes in multiple [18F]fluorodeoxyglucose positron emission
tomography * computed tomography ([18F]FDG PET-CT) scans in one patient,
test-retest variability needs to be determined, to know when an observed
difference is due to a true biological effect.The aim of the present study is
to further measure the test-retest reproducibility of [18F]FDG PET-CT whole
body scans in patients with malignant lung lesions. In this study the impact of
using different tracer uptake periods and use of state of the art PET-CT
technology of tracer uptake quantification and delineation using various new
methodologies will be explored. Moreover, test-retest variability of 1D, 2D and
volumetric tumor size measurements will be assessed.

This study is a single centre, prospective observational study. 12 eligible
patients with malignant lung lesions will be included and will undergo two
[18F]FDG PET-CT scans on two separate occasions (within one week), without
intervening therapy. The whole body PET scans will be performed on a Philips
Gemini TF PET-CT scanner. Personal and tumour characteristics will be
registered (age, sex, body weight, body height and medication).

The venous cannulas will be placed by highly qualified medical doctors of the
Department of Nuclear Medicine & PET Research. In spite of this, occasionally
these cannulas may cause a hematoma. A PET scan is a regular diagnostic imaging
technique. Each study will be conducted in compliance with the radiation
safety guidelines of the department. Based on results we obtained from
biodistribution studies in rats, whole body radiation after intravenous
injection of 185 MBq [18F]FDG is approximately 8 mSv, including the low dose
CT used for attenuation correction. Patients will undergo two [18F]FDG PET
scans, together with a diagnostic CT thorax with intravenous contrast (5 mSv).
The total amount of radiation burden will be approximately 26 mSv during the
entire study. To compare, every person living in the Netherlands receives a
natural background radiation dose of 2-2,5 mSv per year.

We are aware that the radiation burden for this study is high, but are of the
opinion that this is acceptable for this particular study (with this specific
population and high scientific impact). Patients will very likely receive
chemoradiation therapy as part of the best standard of care. The radiation
burden from the treatment will be a multitude higher than the radiation dose
from the diagnostic work-up and the presently suggested TRT study. In addition,
the results of this study will have great clinical benefit in using [18F]FDG
PET-CT as response evaluation tool in the future, improving personalized
therapy strategies for cancer patients. We therefore consider the additional
radiation burden acceptable and we feel that it outweighs the scientific merit
of results that come from the suggested study.