Dual isotope stress Tl-201 and rest Tc-99m CZT SPECT: Are we truly leveraging CZT technology?
Dual isotope stress Tl-201 and rest Tc-99m CZT SPECT: Are we truly leveraging CZT technology?
Saurabh Malhotra 0
FASNC 0 3
Rami Doukky 0
FASNC 0 1 2
0 Reprint requests: Rami Doukky , MD, MSc, FASNC , Division of Cardiology, Cook County Health and Hospitals Systems , 1901 W. Harrison St., Suite 3620, Chicago, IL 60612 , USA
1 Division of Cardiology, Cook County Health and Hospitals Systems , Chicago, IL , USA
2 Division of Cardiology, Rush University Medical Center , Chicago, IL , USA
3 Division of Cardiovascular Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY , USA
Conventional Anger cameras with NaI technology form the backbone of majority of the radionuclide imaging laboratories. The design of the conventional Anger camera suffers from major limitations, such as low photon sensitivity and low inherent spatial resolution, requiring relatively higher doses of radioisotope and longer imaging times to provide diagnostic quality images. The introduction of solid-state technology has revolutionized myocardial perfusion imaging (MPI). The majority of the solid-state cameras use CadmiumZinc-Telluride (CZT) semiconductor for photon detection. These semiconductors combine the functions of scintillation crystal and photomultiplier tubes and produce current directly in response to the photons. CZT crystals can process [ 10 million photons/second/mm2 and thus provide a greater photon sensitivity with improved energy resolution compared to conventional NaI crystal. This higher energy resolution conferred by CZT cameras translates into improved image resolution and for diagnostic imaging to be performed with low to very low dose of radiotracer. Results from the MILLISIEVERT study highlight the fact that ''ultra-low-dose'' imaging using only 3.5 mCi of Tc-99m (1 mSv) can be performed with solid-state cameras, with a superior image quality and similar diagnostic accuracy when compared to standard anger cameras.1 The greater
sensitivity of the CZT cameras allows for ultra-fast
imaging (1-2 minutes) with standard doses of
radioisotopes, thus providing the ability to improve laboratory
throughput. Novel protocols for SPECT imaging with
varying combination of isotope type, dose, and imaging
times have been reported and can provide laboratories
employing CZT technology significant flexibility in
performing appropriate, patient-centered imaging with
high diagnostic accuracy.
The higher sensitivity, improved image resolution
and reduction in radiation have translated beyond
Tc99m tracers, with the provision of performing ‘lower’
dose dual isotope protocols as well. Though not
recommended,2 reports of imaging with dual isotope
protocols with CZT cameras, at half the dose when
compared to conventional Anger cameras, have been
reported. In a study of 102 patients undergoing stress/
rest Tc-99m MPI on a CZT camera, Imbert et al.
performed additional Tl-201 imaging at rest.3 The authors
reported a comparable accuracy for detection of
myocardial ischemia when comparing data from dual
isotope stress/rest imaging (AUC = 0.83 ± 0.03) vs.
single isotope stress/rest imaging (AUC = 0.81 ± 0.03).
Importantly, the authors employed an ultra-low dose
Tc99m (1 mSv) for stress, and low-dose rest Tc-99m (3.3
mSv) or a low-dose rest Tl-201 (7.3 mSv). The authors
further reported that close to 40% of studies at their
institution are performed as stress-only, suggesting that
effective stress MPI with CZT can be performed at 1
mSv of radiation exposure. Other studies have also
reported the ability to perform of a diagnostic SPECT
MPI with low or ultra-low radioisotope dose on a CZT
In this issue of the Journal, Barone-Rochette et. al,
report the performance of a dual isotope stress Tl-201/
rest Tc-99m protocol employing Discovery NM 530c
CZT camera (GE Healthcare) in 54 patients being
evaluated for coronary artery disease (CAD).7 All
patients enrolled in this study were scheduled to undergo
a clinically indicated invasive coronary angiogram
(ICA), with fractional flow reverse (FFR) assessment for
intermediate stenosis (50-90%). Each patient underwent
Tl-201 stress-first with supine (gated) and prone
imaging, followed by a supine Tc-99m resting SPECT
(gated). The lowest possible, weight-based, dose of the
isotopes used was 2 mCi for Tl-201 and 8 mCi for
Tc99m, which approximates to 11.5 mSv of radiation
exposure (8.8 mSv if stress-first or stress-only imaging is
performed).8 The authors report a good sensitivity of
this dual isotope protocol to detect hemodynamically
significant CAD, though with a suboptimal specificity.
Despite similar dosimetry when compared to a single
isotope Tc-99m protocol on a conventional Anger
camera, dual isotope imaging confers a few advantages.
The improved sensitivity and spatial resolution of the
CZT cameras allowed for faster acquisition of high
quality stress images with relatively lower Tl-201 dose
(2 mCi) compared to 2.5-3.5 mCi administered with
conventional Anger camera, yielding relatively lower
effective dose of radiation.8 Since Tl-201 stress imaging
is performed first, Tc-99m down-scatter in the Tl-201
energy window is avoided. As reported in the current
study, the imaging times were approximately 20 minutes
for the entire study. This higher throughput is a
definitive advantage over conventional rest/stress single
isotope protocols. The second, theoretical, advantage
pertains to the use of Tl-201 itself, which has a superior
extraction fraction, thus potentially allowing for
detection of perfusion defects with a greater sensitivity. Per
Barone-Rochette et al., this forms the main premise of
performing dual isotope CZT SPECT.
In contemporary practice of nuclear cardiology, we
are continuously striving to provide excellent diagnostic
capabilities, and application CZT technology is a big
step in this direction. However, the use of dual isotope
protocols seems retrogressive in this regard and does not
fully mine the flexibility conferred by CZT cameras. As
nuclear cardiologists, our goal is to provide accurate
diagnostic, prognostic, and therapeutic guidance to our
referral base, while maintaining laboratory efficiency,
improving image quality, and reducing radiation
exposure. Imaging with Tl-201 does offer the theoretical
advantage of better sensitivity due to greater extraction
fraction when compared to Tc-99m, though this
presumed diagnostic superiority, reported in animal
studies,9,10 has not been consistently documented in
clinical scenarios.11-14 In a small study (n = 38) of
patients who had undergone ICA, Cramer et al.
performed Tc-99m and Tl-201 imaging, in random order,
and noted no clinically relevant differences in diagnostic
accuracy between the two tracers. In another small study
of 26 patients undergoing both Tc-99m and Tl-201
SPECT, there was a similar number of fixed defects
identified by both tracers.15 Though Tl-201 identified a
greater number of reversible defects, they were
predominantly from regions with mild coronary artery
disease. A more recent, larger study, of 163 patients with
mild to moderate CAD (50%-89%) on ICA, compared
the diagnostic performance of Tl-201 (n = 69), Tc-99m
sestamibi (n = 50) and Tc-99m tetrofosmin (n = 44).12
The authors reported no differences in the summed
uptake scores between the three tracers and the percent
of abnormal territories identified by them—Tl-201: 62%
vs. Tc-99m sestamibi: 57% vs. Tc-99m tetrofosmin:
58%, P = 0.8, suggesting a comparable diagnostic value
of all three tracers. While these studies were performed
on conventional Anger camera, subgroup analysis of a
more recent CZT-based study (n = 230) also showed no
statistical difference in the diagnostic accuracy of
Tc99m (68%) or Tl-201 (71%) SPECT for anatomical
CAD (C 70% stenosis).16
Maintaining laboratory efficiency is challenging,
especially for nuclear medicine laboratories that also
perform MPI. A higher throughput offered by a dual
isotope protocol is certainly attractive in this regard.
Though this may be true for conventional Anger
systems, it does not fully harness the abilities of a CZT
camera, wherein imaging can be completed within a few
minutes with conventional rest and stress doses of
Tc99m. Laboratories where there are fewer constraints on
throughput can perform low dose rest and stress imaging
at significantly lower radiation exposure. Additionally,
the rapidity with which imaging can be accomplished
with CZT systems allows for low dose stress-first
protocols to be implemented. This allows for rapid, accurate
assessment of myocardial perfusion at a fraction of the
conventional dose, with the ability to perform a ‘higher
dose’ resting scan if stress-first is abnormal. Moreover,
the need for performing a resting scan can be obviated
by careful selection of patients (low risk) and subjecting
them to a stress-only protocol. An algorithm of selection
of such patients for CZT SPECT has been suggested by
Duvall et. al.16
In this editorial, we provide a distribution of the
approximate radiation exposure from a variety of MPI
protocols reported in the literature (Figure 1). We
strongly believe that though newer camera technology
has greatly enhanced the field of nuclear cardiology,
technological advancements alone are not sufficient to
provide patient-centered imaging—appropriate and
effective, with low radiation exposure. A laboratory
should be armed with a gamut of imaging protocols
(rest/stress, stress/rest, stress-first and stress-only, etc.)
that should cater to the needs and demographics of
patients being imaged. Careful preselection of patients is
critical, and as shown in the figure, can result in
significant radiation dose reduction, even with conventional
Anger camera, with a greater impact with
high-resolution CZT systems. Thus, given the lack of clinically
significant difference in diagnostic accuracies of a dual
isotope vs. single isotope protocol, the considerable
improvement in image quality and the improved
laboratory throughput conferred by solid-state detector
systems, it would be regressive to implement a dual
isotope protocol on a CZT camera.
Rami Doukky receives research funding grants from
Astellas Pharma (Northbrook, IL) and serves on an advisory
board for Astellas Pharma. Saurabh Malhotra has nothing to
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