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Imaging characteristics of 124I between 3D and 2D on siemens ECAT HR + PET scanner


Abstract and Figures

I has a complex decay scheme with high gamma energy and low positron abundance. In this study, comparative performance measurements of I were performed in terms of spatial resolution, sensitivity, and image quality. All measurements were performed using both 2D and 3D PET in both brain mode and whole body mode. The transverse and axial spatial resolutions at 1 cm were 5.56 and 6.07 mm for I, and were 4.58 and 4.77 mm and for F, respectively. Sensitivities were 0.5 kcps/MBq (2D) and 3.4 kcps/MBq (3D) for I, and 1.8 kcps/MBq (2D) and 9.8 kcps/MBq (3D) for F. The %contrast of 3D was higher than that of 2D in I. For I PET imaging, 3D acquisition with brain mode was highest achievable imaging acquisition mode with finer spatial res-olution and higher contrast. This result will be useful for I PET imaging Index Terms—Image quality, reconstruction algorithms, spatial resolution, whole-body PET.
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Imaging Characteristics of I Between 3D and
2D on Siemens ECAT HR PET Scanner
YoungSubLee, JinSuKim, Hee-JoungKim, Member, IEEE, Sang-Keun Woo, Jong Guk Kim, Ji Ae Park,
Chang Woon Choi, Sang Moo Lim, and Kyeong Min Kim, Member, IEEE
Abstract— I has a complex decay scheme with high gamma
energy and low positron abundance. In this study, comparative
performance measurements of I were performed in terms of
spatial resolution, sensitivity, and image quality. All measurements
were performed using both 2D and3DPETinbothbrainmodeand
whole body mode. The transverse and axial spatial resolutions at 1
cm were 5.56 and 6.07 mm for I, and were 4.58 and 4.77 mm and
for F, respectively. Sensitivities were 0.5 kcps/MBq (2D) and 3.4
kcps/MBq (3D) for I, and 1.8 kcps/MBq (2D) and 9.8 kcps/MBq
(3D) for F. The %contrast of 3D was higher than that of 2D in
I. For I PET imaging, 3D acquisition with brain mode was
highest achievable imaging acquisition mode with ner spatial res-
olution and higher contrast. This result will be useful for IPET
Index Terms—Image quality, reconstruction algorithms, spatial
resolution, whole-body PET.
information on both functional and biochemical processes
in vivo. F-uorodeoxyglucose (FDG) PET has been routinely
used to diagnose cancer or neurodegenerative diseases. Besides
the F-labeled tracer, many radiopharmaceutical such as C
(half life, 20.4 min), N (half life, 10 min), and O(halflife,
2 min) were also used for PET imaging. Recently, the use of I
has increased because I is a PET tracer that may be used in
personalized dosimetry for I radionuclide [1]–[3]. IPET
can be used to assess the risks and benets of newly developed
radioisotopes in therapy. Although I has many advantages,
the imaging characteristics of I should be assessed due to the
complex decay scheme of I (602, 723 and 1691 keV) and its
fraction emitted from I was tabulated in Table I.
Manuscript received June 15, 2012; revised November 20, 2012 and January
03, 2013; accepted January 09, 2013. Date of publication February 20, 2013;
date of current version April 10, 2013. This work was supported by grants from
the Nuclear R&D Program (2010-0017587 and 2011-0002286) of the Korea
Science and Engineering Foundation funded by the Ministry of Education, Sci-
ence, and Technology, and supported by grants from the National Research
Foundation (2012013722) of the Korea. (Corresponding author: J. S. Kim.)
Y. S. Lee is with the Korea Institute Radiological and Sciences, Seoul 139-
706, Korea, and also with the Department of Radiological Science, Yonsei Uni-
versity, Wonju 220-710, Korea.
K. M. Kim are with the Korea Institute Radiological and Sciences, Seoul 139-
706, Korea (e-mail:
H.-J. Kim is with the Department of Radiological Science, Yonsei University,
Wonju 220-710, Korea.
Color versions of one or more of the gures in this paper are available online
Digital Object Identier 10.1109/TNS.2013.2240012
In I, high energy photons (602, 723 and 1691 keV) are
emitted in a cascade with positrons. Therefore, the PET image
quality is degraded due to cascade photons. Cascade photons
contribute to background image noise in IPET.
Although there were previous reports on the imaging charac-
teristics of I [1], [2], [4] to the best of our knowledge, there
was no report on comparative imaging studies such as image
qualities of IinSiemensECATHR scanner using brain
mode and whole body mode and with 2D and 3D acquisition
The goal of the present study was the comparison of imaging
characteristics between 3D and 2D in I PET in terms of
image quality to determine the highest achievable PET acquisi-
tion mode for I PET. All experiments were performed using
the brain and whole body modes. The brain mode was designed
for brain PET imaging in which high resolution is provided and
the pixel dimensions is brain mode meet the National Electrical
Manufacturers Association (NEMA) guidelines. In whole body
PET, the pixel dimension was greater than the NEMA require-
ment [5], [6].
Regarding internal dosimetry for I PET [2], whole body
PET scan is needed. In contrast, high resolution PET scan would
be suitable when regional PET for thyroid scan was performed.
Therefore, assessment of imaging characteristics of I for both
brain mode and whole body mode would be needed to interpret
In addition, we measured the spatial resolution and sensi-
tivity of I PET, and then compared with that of F, because
F could be regarded as a gold-standard for the comparison of
imaging characteristics.
To assess the imaging characteristics of Iand F, th e s p a -
tial resolution and image quality were measured on an ECAT
0018-9499/$31.00 © 2013 IEEE
HR scanner partly according to the NEMA NU2-2007 stan-
dards [6].
A. System Description
ASiemensECATHR PET scanner was used in this study.
The ECAT HR scanner has retractable septa and can be op-
erated using 2D and 3D PET acquisition modes. The coinci-
dence time window was set to 12 ns, and the energy resolution
was 26%. PET data were acquired within an energy window of
350–650 keV for the brain and whole body modes.
B. Spatial Resolution
The spatial resolution of the system was dened as the ability
to distinguish between two points on an image. To compare
the spatial resolution between Iand F, a point source
(diameter, 1.1 mm) was made. The total activity was
MBq for each acquisition. To measure the spatial resolution
of I, a tissue-equivalent material was wrapped to the point
source to avoid positron escape. Tissue-equivalent material
composed of slabs of parafnwax,ricebagslled with soda,
gauze coated with petrolatum, and synthetic-based substances.
This tissue-equivalent material was called as Bolus. Point
source was wraped with Bolus (thickness: 5 mm and length:
10 cm) to avoid positron escape. The point source was located
at the center of the axial eld of view (FOV) and offset 1/4
axial FOV from the center. The point source was positioned at
three locations in the transaxial plane as follows: cm,
cm; cm, cm; and cm,
cm. Therefore, data were acquired at 6 positions using brain
mode and whole body mode, respectively. At each position,
at least one hundred thousand counts were acquired to ensure
enough counts. The images were reconstructed in both brain
and whole body mode using the 2D acquisition mode. For
reconstruction, ltered back projection (FBP) with ramp lter
was used according to NEMA NU2-2007 standards [6]. The
pixel size of the reconstructed image was 0.51 0.51 mm for
the brain mode and 3.96 3.96 mm for the whole body mode.
The spatial resolution was calculated for each point source
position as full width at half maximum (FWHM) and full width
at tenth maximum (FWTM) of the point spread function deter-
mined in all 3 directions. Radial and tangential resolutions for
each radial position (1 and 10 cm) were averaged for both axial
positions according to NEMA NU2-2007 standards [6].
C. Sensitivity
The sensitivity is expressed as counts per second where true
coincidence events are detected for a given source strength
(count/sec/MBq). The sensitivity was measured using a NEMA
sensitivity phantom [6], a mm plastic tubing (inner
diameter, ID: 0.8 mm; outer diameter, OD: 3 mm; length, 70
mm) lled with Iand F surrounded 5 concentric aluminum
sleeves (ID: 0.39, 0.7, 1.02, 1.34, and 1.66 cm), the scanned
center of FOV and a 10-cm offset from the center. The sensi-
tivity phantom was scanned in 2D and 3D acquisition modes,
and the PET acquisition time was 600 s. Initial activities for
Iand F were 4.625 MBq and 4.107 MBq, respectively.
The total system sensitivity was calculated by dividing the
Fig. 1. Determined of by tting natural logarithm of the measured counting
rates as function of the sleeve thickness for Iand F.
total count rate in the absence of attenuating material
at corresponding activity. was determined by tting the
natural logarithm of the measured counting rates as a function
of the sleeve thickness (Fig. 1).
D. Image Quality
To assess the image quality of Iand F, the N E M A I n -
ternational Electrotechnical Commission (IEC) body phantom
was used [6]. The NEMA IEC body phantom consists of 6 hot
spheres (ID, 10, 13, 17, 22, 28, and 37 mm) that were lled
with Ior F solution [7]. The activity concentration in the
background was 5.3 kBq/cc and the activity concentration in the
spheres was 4 times that of the background activity for both I
and F. The energy window was 350–650 keV.
PET data were acquired for 320 s for both Iand F. The
number of coincidences used to reconstruct the image was 6
Mcounts (for 2D, F), 29 Mcounts (for 3D, F), 2 Mcounts
(for 2D, I), and 16 Mcounts (for 3D, I).
Although the larger 2 spheres (ID, 28 and 37 mm) were lled
with nonradioactive water according to NEMA NU2-2007,
in this study all spheres were lled with radioactive water to
assess the %contrast in the largest 2 spheres. The phantom was
positioned at the axial and transaxial center of the scanner FOV.
PET data were acquired using 2D and 3D modes, as well as
both the brain and whole body modes. Transmission PET was
acquired for 105 sec using Ge source (activity: MBq).
Data were corrected for random coincidence, normalization,
dead-time loss, scatter, and attenuation. The OSEM algorithm
(iteration, 2; subset: 16), with Hanning lter and default clinical
setting, was used for reconstruction. Pixel size was 0.51 0.51
mm for the brain mode and 3.96 3.96 mm for the whole
body mode. To assess the image quality, %contrast, and percent
background variability (%BV) were measured.
Percent Contrast (%Contrast): To calculate %contrast, the
transverse image of the IEC phantom was used in the anal-
ysis. Regions of interest (ROIs) were drawn on each sphere.
The size of ROIs was equal to the inner diameter of the sphere.
Twelve ROIs were drawn in the background using the same size
of spheres ROI in the IEC phantom. The ROIs were drawn on
slices on the center slice. Twelve ROIs were drawn on each
slice, where a total of 60 background ROIs were drawn on 5
slices. The %contrast for sphere j was calculated as follows:
where is the average counts in ROI for sphere j, is
the average of the background ROI counts for sphere, a is the
activity concentration in the spheres, and is the activity con-
centration in the background.
Percent Background Variability (%BV): The %BV for
sphere j was calculated by
where was the standard deviation of the background ROI
counts for sphere j. SD was calculated as follows:
In this study, the imaging characteristics of Iand Fwere
measured in terms of spatial resolution, sensitivity and image
quality according to NEMA NU2-2007 standards. Both 2D and
3D acquisition modes were used in the measurements.
A. Spatial Resolution
The transverse and axial resolution at an offset of 1 cm from
the center was 5.56 cm and 6.07 cm (brain mode) and 9.74 cm
and 10.61 cm (whole body mode) for I, and 4.58 cm and 4.77
cm (brain mode) and 8.55 cm and 9.12 cm (whole body mode)
for F. The spatial resolution of Iwaslowerthanthatof F.
The spatial resolutions of Iand Finbrainmodeandwhole
body modes are shown in Table II.
Fig. 2. Images of IEC body phantom 2D Brain mode (A), 2D Whole body
mode (B), 3D Brain mode (C), and 3D Whole body mode (D) for I and 2D
Brain mode (E), 2D Whole body mode (F), 3D Brain mode (G), and 3D Whole
body mode (H) for F.
B. Sensitivity
Sensitivities were 0.5 kcps/MBq (2D) and 3.4 kcps/MBq
(3D) for I, and 1.8 kcps/MBq (2D) and 9.8 kcps/MBq (3D)
for F. The branching ratios were not corrected.
C. Image Quality
Fig. 2 shows the PET image for the assessment of image
quality for both Iand F.
Percent Contrast (%Contrast): The %contrasts of Iand
F in brain and whole body mode are Fig. 3(A) and (B). %con-
trast of 3D was higher than that of 2D in I. %contrast of I
was lower than that of F.
Percent Background Variability (%BV): The %BVs of I
and F in brain and whole body modes are shown in Fig. 3(C)
and (D). The %BV of 2D was higher than that of 3D in I.
The %BV of I was higher than that of F. % BV of I-124
was worsened by 7% for 2D brain, 15% for 2D WB, 13% for
3D brain, and 21% for 3D WB.
In this study, we assessed the spatial resolution, sensitivity
and image quality of Iand F. A comparative study was
also performed for both brain and whole body modes and for
2D and 3D acquisitions.
A. Spatial Resolution
We assessed the effects of pixel size and the positron range on
spatial resolution. First, we used brain and whole body modes to
observe the effect of pixel size. Pixel size was 0.51 0.51 mm
in brain mode and 3.96 3.96 mm in whole body mode. In the
NEMA NU2-2007 guidelines [6], the pixel size should be
of the expected spatial resolution. Because the expected spatial
resolution was 4–5 mm in ECAT HR , the pixel size in whole
body mode was too coarse to measure the spatial resolution in
the ECAT HR scanner. Table 3 shows the result of the spatial
resolution at each condition. We found that the spatial resolu-
tion was 9.74–10.91 mm for I and 8.5–9.9 mm for Fin
Fig. 3. Image qualities of IEC body phantom using Iversus
F, % contrast of I (A), % contrast of F (B), % BV of
I(C),%BVof F(D),%
% .
the whole body mode and 5.56–6.72 mm for I and 4.58–5.18
mm for F in the brain mode. For an actual PET scan such as
pre-therapeutic I PET dosimetry, the spatial resolution of the
whole body mode PET scan would be more informative than the
result according to NEMA guidelines. Second, regarding the ef-
fect of the positron range, we compared the spatial resolutions
of Iand F. The transverse spatial resolution at an offset
of 1 cm was 5.56 mm for I and 4.58 mm for F, respec-
tively. Worse resolution was observed with I compared to
F, which is attributed to the longer positron range of I[8].
Theoretically, the transverse resolution corrected for source
dimension for both Iand FonECATHR scanner can be
calculated with the following equation [9], [10];
Where is the dimension of the crystal element(s) and
is the ring diameter, p is the positron range (
mm for Iand F) [11], and b is the block factor (assumed to
zero) [12]. The theoretical spatial resolution value is 5.10 mm
for I and 3.94 mm for F. In our measurements, the spa-
tial resolution with source dimension correction was 5.46 mm
for I and 4.46 mm for F. Our spatial resolution measure-
ments compared well with the predicted values. Small differ-
ences are attributed to the presence of block factor in the actual
PET scanner.
The FWHM/FWTM ratio was 0.54 for I and 0.62 for F,
indicating a larger tail for I. In I, the coincidence between
the annihilation photons and correlated single cascade photons
with energy above the lower discriminator value of the energy
window will contribute to a uniform background in the recon-
structed image. The larger tail is probably due to the uniform
background in I.
B. Sensitivity
The sensitivity is affected by many factors such as axial FOV
and the image acquisition method. With regard to the sensitivity
comparison between Iand F, the sensitivity of Fwas3.6
times higher than that of I in 2D and 2.8 times higher in 3D.
The smaller difference of sensitivity in 3D was due to greater
inclusion of correlated single cascade photons in 3D PET. In
2D PET, septa preclude the inclusion of corrected single cascade
photons. With respect to the sensitivity comparison between
2D and 3D, the 3D sensitivity was 5.4 times higher than that
of 2D for F and 6.8 times for I. This tendency was similar
to previous results. In previous studies, the 3D sensitivity was
4–6 times higher than the 2D sensitivity. The larger sensitivity
difference for I was due to greater inclusion of correlated
single cascade photons.
C. Image Quality
In this paper, the image quality of Iand F was assessed in
terms of %contrast, and %BV. All experiments were performed
in 2D and 3D, and brain and whole body modes.
Percent Contrast (%Contrast): The %contrast of Iwas
lower than that of F. The lower %contrast was probably due
to higher positron range of I. The %contrast of 3D was higher
than that of 2D for both Iand F. This tendency was also
found in a previous study [13]. In addition, the difference be-
tween 2D and 3D was larger in Ithanin F. In I, %
contrast of 2D was worsened by 41% for brain mode and 29%
for whole body mode compare to that of 3D. In F, the differ-
ence between 2D and 3D was 1.5% for brain mode and 10% for
whole body mode. For I, the difference was more signicant
in brain mode.
The %contrast in the brain mode was higher than that in
whole body mode.
We co ul d nd that %contrast of 3D was higher than that of 2D
and %contrast of brain mode was higher than that of whole body
mode. The higher %contrast in 3D or brain mode was due to
better spatial resolution. In this study, the spatial resolution was
measured in 2D mode. According to the Adam et al.,’s result,
the spatial resolution at center was 4.5 mm for 2D and 4.3 mm
for 3D. The spatial resolution at center in 3D was higher than
that of 2D [14].
Percent Background Variability (%BV): Regarding the com-
parison between 2D and 3D, the %BV of 3D was equivalent to
2D for both Iand F. The %BV in the brain mode was ap-
proximately higher than that in the whole body mode. The %BV
of I was higher than that of F.
In this study, we compared imaging characteristics of I
and F. At center of FOV, the spatial resolution of Iwas
worsened by 19% for brain mode and 13% for whole body mode
compared to that of F. In addition, the spatial resolution of I
at whole body mode was worsened by 54% compare to that of
brain mode.
We compared the image characteristics such as % contrast,
% background variability of Iand F using various image
acquisition conditions including 2D and 3D, and the brain and
whole body modes. For I PET imaging, 3D acquisition with
brain mode was highest achievable imaging acquisition mode
with ner spatial resolution and higher contrast. This result will
be useful for I PET imaging.
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... For example, a line source of I-124 yields a spatial resolution defined by the fullwidth-at-half-maximum image intensity of *5-6 mm for human PET scanner detector configurations. [53][54][55][56] Later time point images were registered with day 0 images using a manual rigid transformation. For whole-body measurements, an effective half-life of I-124 (T 1/2 eff ) was calculated by fitting a monoexponential function to the longitudinal data. ...
A method is presented for quantitative analysis of the biodistribution of adeno-associated virus (AAV) gene transfer vectors following in vivo administration. We used iodine-124 (I-124) radiolabeling of the AAV capsid and positron emission tomography combined with compartmental modeling to quantify whole-body and organ-specific biodistribution of AAV capsids from 1 to 72 h following administration. Using intravenous (IV) and intracisternal (IC) routes of administration of AAVrh.10 and AAV9 vectors to nonhuman primates in the absence or presence of anticapsid immunity, we have identified novel insights into initial capsid biodistribution and organ-specific capsid half-life. Neither I-124-labeled AAVrh.10 nor AAV9 administered intravenously was detected at significant levels in the brain relative to the administered vector dose. Approximately 50% of the intravenously administered labeled capsids were dispersed throughout the body, independent of the liver, heart, and spleen. When administered by the IC route, the labeled capsid had a half-life of ∼10 h in the cerebral spinal fluid (CSF), suggesting that by this route, the CSF serves as a source with slow diffusion into the brain. For both IV and IC administration, there was significant influence of pre-existing anticapsid immunity on I-124-capsid biodistribution. The methodology facilitates quantitative in vivo viral vector dosimetry, which can serve as a technique for evaluation of both on- and off-target organ biodistribution, and potentially accelerate gene therapy development through rapid prototyping of novel vector designs. (phanwiki)
... The factors that determine RC include the size of the lesion. The factors determining the spatial resolution in the image are the matrix size of the image, the image reconstruction method, and the filter [24]. The NU is an index that measures the uniformity of an image. ...
Full-text available
The goal of this study was to suggest criteria for the determination of the optimal image reconstruction algorithm for image-based dosimetry of Cu-64 trastuzumab PET in a mouse model. Image qualities, such as recovery coefficient (RC), spill-over ratio (SOR), and non-uniformity (NU), were measured according to National Electrical Manufacturers Association (NEMA) NU4-2008. Mice bearing a subcutaneous tumor (200 mm 3 , HER2 NCI N87) were injected with monoclonal antibodies (trastuzumab) with Cu-64. Preclinical mouse PET images were acquired at 4 time points after injection (2, 15, 40 and 64 h). Phantom and Cu-64 trastuzumab PET images were reconstructed using various reconstruction algorithms (filtered back projection (FBP), 3D reprojection algorithm (FBP-3DRP), 2D ordered subset expectation maximization (OSEM 2D), and OSEM 3D maximum a posteriori (OSEM3D-MAP)) and filters. The absorbed dose for the tumor and the effective dose for organs for Cu-64 trastuzumab PET were calculated using the OLINDA/EXM program with various reconstruction algorithms. Absorbed dose for the tumor ranged from 923 mGy/MBq to 1830 mGy/MBq with application of reconstruction algorithms and filters. When OSEM2D was used, the effective osteogenic dose increased from 0.0031 to 0.0245 with an increase in the iteration number (1 to 10). In the region of kidney, the effective dose increased from 0.1870 to 1.4100 when OSEM2D was used with iteration number 1 to 10. To determine the optimal reconstruction algorithms and filters, a correlation between RC and NU was plotted and selection criteria (0.9 < RC < 1.0 and < 10% of NU) were suggested. According to the selection criteria, OSEM2D (iteration 1) was chosen for the optimal reconstruction algorithm. OSEM2D (iteration 10) provided 154.7% overestimated effective dose and FBP with a Butterworth filter provided 20.9% underestimated effective dose. We suggested OSEM2D (iteration 1) for the calculation of the effective dose of Cu-64 trastuzumab on an Inveon PET scanner.
... They have also shown that 18 F-FDG has the highest resolution of all isotopes studied, followed by 89 Zr, mainly because of their relatively shorter positron range [13]. A previous study carried out by Lee et al. [16] has showed that the spatial resolution of 124 I was degraded by 19.9% compared with that of 18 F-FDG on the ECAT HR + scanner (Siemens Healthcare GmbH). ...
Purpose: Interest in PET imaging using zirconium-89 (Zr) (t1/2=78.41 h)-labeled tracers for the tracking and quantification of monoclonal antibodies (mAbs) is growing, mainly because of its well-matched physical half-life with the biological half-life of intact mAbs. This study aims to evaluate the imaging characteristics of Zr-PET in comparison with those obtained using fluorine-18 fluorodeoxyglucose (F-FDG) PET (gold standard tracer in PET imaging) using a Time-Of-Flight (TOF) PET/computed tomography (CT) scanner. Materials and methods: The system's spatial resolution, sensitivity, scatter fraction (SF), image uniformity, and image quality were measured on a Gemini TOF PET/CT scanner according to the NEMA NU2-2001 protocols. The NEMA 2001 kit was used to carry out these measurements. Timing and energy resolutions were measured using Na and F-FDG point sources only. Results: Spatial resolution in transverse and axial planes measured at 10 mm off access were 4.7 and 4.6 mm for Zr and F-FDG, respectively. At 100 mm, radial, tangential, and axial spatial resolution values were 5.2, 5.1, and 5.2 mm for Zr and 5.1, 4.9, and 5.2 mm for F-FDG, respectively. Sensitivity measured at the center of the field of view was 14.6 and 4.16 cps/kBq for Zr and F-FDG, respectively. SF was 32.6% for Zr in comparison with 31.8% for F-FDG. Image contrast for Zr-PET images was 36.9 and 29.7% for F-FDG for the smallest (10 mm)-sized sphere, and it was 70.6 and 72.8% for Zr and F-FDG, respectively, for the largest (37 mm)-sized sphere. Background variation was 10.3% for Zr and 6.8% for F-FDG for the smallest-sized sphere and 3.4 and 3.8% for Zr and F-FDG, respectively, for the largest-sized sphere. Conclusion: In this study, we measured imaging characteristics of Zr on a Gemini TOF PET/CT scanner. Our results show that Zr has lower spatial resolution and noise-equivalent count rate with increased SF and background variation; however, it offered superior sensitivity and improved image contrast in comparison with F-FDG. Zr is an ideal radiotracer for immuno-PET imaging because of its physical half-life, which is well matched with mAbs, in addition to its affinity to be trapped inside the target cell after internalization of the mAbs.
... Jin Su Kim's group in Korea Institute of Radiological and Medical Sciences (KIRAMS) reported that the spatial resolution of 124 I was reduced by 19 % compared with that of 18 F on the ECAT HR+ scanner. The PET image quality with this radionuclide is poor owing to the cascade of γ photons and low β + branching ratio (β + branching ratio of 124 I, 23 %) [16,17]. High-energy γ photons (602, 723, and 1691 keV) are emitted in a cascade with the β + The major interference is caused by γ photons with energy levels of 602 keV because their energy level falls within the standard energy window of most PET scanners, which will detect these photons as additional background noise or interference. ...
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Monoclonal antibodies (mAbs), which play a prominent role in cancer therapy, can interact with specific antigens on cancer cells, thereby enhancing the patient’s immune response via various mechanisms, or mAbs can act against cell growth factors and, thereby, arrest the proliferation of tumor cells. Radionuclide-labeled mAbs, which are used in radioimmunotherapy (RIT), are effective for cancer treatment because tumor associated-mAbs linked to cytotoxic radionuclides can selectively bind to tumor antigens and release targeted cytotoxic radiation. Immunological positron emission tomography (immuno-PET), which is the combination of PET with mAb, is an attractive option for improving tumor detection and mAb quantification. However, RIT remains a challenge because of the limited delivery of mAb into tumors. The transport and uptake of mAb into tumors is slow and heterogeneous. The tumor microenvironment contributed to the limited delivery of the mAb. During the delivery process of mAb to tumor, mechanical drug resistance such as collagen distribution or physiological drug resistance such as high intestinal pressure or absence of lymphatic vessel would be the limited factor of mAb delivery to the tumor at a potentially lethal mAb concentration. When α-emitter-labeled mAbs were used, deeper penetration of α-emitter-labeled mAb inside tumors was more important because of the short range of the α emitter. Therefore, combination therapy strategies aimed at improving mAb tumor penetration and accumulation would be beneficial for maximizing their therapeutic efficacy against solid tumors.
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Purpose: Zirconium-89 (t(1/2)=78.41 hours) is an ideal metallic radioisotope for immuno-positron emission tomography (PET), given that its physical half-life closely matches the biological half-life of monoclonal antibodies. In this study, the authors measured the spatial resolution and image quality of Zr-89 PET and compared the results against those obtained using F-18 PET, which is widely regarded as the gold standard for comparison of imaging characteristics. Materials and methods: The spatial resolution and image qualities of Zr-89 were measured on the Siemens Biograph Truepoint TrueV PET/CT scanner, partly according to NEMA NU2-2007 standards. For spatial resolution measurement, the Zr-89 point source was located at the center of the axial field of view (FOV) and offset 1/4 axial FOV from the center. For image quality measurements, an NEMA IEC Phantom was used. The NEMA IEC Phantom consists of six hot spheres that were filled with Zr-89 solution. Spatial resolution and image quality (%contrast, %background variability [BV], and source to background ratio [SBR]) were assessed to compare the imaging characteristics of F-18 with those of Siemens Biograph Truepoint TrueV. Results: The transverse and axial spatial resolutions at 1 cm were 4.5 and 4.7 mm for Zr-89, respectively. The %contrast of Zr-89 was 25.5% for the smallest 10 mm sized sphere and 89.8% for the largest 37 mm sized sphere, and for F-18, it was 32.5% for the smallest 10 mm sized sphere and 103.9% for the largest 37 mm sized sphere using the ordered subset expectation maximization (OSEM) reconstruction method. The %BV of F-18 PET was 6.4% for the smallest 10 mm sized sphere and 3.5% for the largest 37 mm sized sphere using the OSEM reconstruction. The SBR of Zr-89 was 1.8 for the smallest 10 mm sized sphere and 3.7 for the largest 37 mm sized sphere, and for F-18, it was 2.0 for the smallest 10 mm sized sphere and 4.1 for the largest 37 mm sized sphere using the OSEM reconstruction method. Conclusions: This study assessed Zr-89 imaging characteristics using a Siemens Biograph Truepoint TrueV PET/CT scanner and compared the results with those obtained for F-18 PET. Although spatial resolution and image quality of Zr-89 PET were lower compared with F-18 PET, due to longer positron range and low positron branching ratio, Zr-89 is advantageous for immuno-PET due to well-matched half-life with monoclonal antibodies.
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It has been shown that I-124 PET imaging can be used for accurate dose estimation in radio-immunotherapy techniques. However, I-124 is not a pure positron emitter, leading to two types of coincidence events not typically encountered: increased random coincidences due to non-annihilation cascade photons, and true coincidences between an annihilation photon and primarily a coincident 602 keV cascade gamma (true coincidence gamma-ray background). The increased random coincidences are accurately estimated by the delayed window technique. Here we evaluate the radial and time distributions of the true coincidence gamma-ray background in order to correct and accurately estimate lesion uptake for I-124 imaging in a time-of-flight (TOF) PET scanner. We performed measurements using a line source of activity placed in air and a water-filled cylinder, using F-18 and I-124 radio-isotopes. Our results show that the true coincidence gamma-ray backgrounds in I-124 have a uniform radial distribution, while the time distribution is similar to the scattered annihilation coincidences. As a result, we implemented a TOF-extended single scatter simulation algorithm with a uniform radial offset in the tail-fitting procedure for accurate correction of TOF data in I-124 imaging. Imaging results show that the contrast recovery for large spheres in a uniform activity background is similar in F-18 and I-124 imaging. There is some degradation in contrast recovery for small spheres in I-124, which is explained by the increased positron range, and reduced spatial resolution, of I-124 compared to F-18. Our results show that it is possible to perform accurate TOF based corrections for I-124 imaging.
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This study evaluates the performance of the newly developed high-resolution whole-body PET scanner ECAT EXACT HR+. The scanner consists of four rings of 72 bismuth germanate block detectors each, covering an axial field of view of 15.5 cm with a patient port of 56.2 cm. A single block detector is divided into an 8 x 8 matrix, giving a total of 32 rings with 576 detectors each. The dimensions of a single detector element are 4.39 x 4.05 x 30 mm3. The scanner is equipped with extendable tungsten septa for two-dimensional two-dimensional measurements, as well as with three 68Ge line sources for transmission scans and daily quality control. The spatial resolution, scatter fraction, count rate, sensitivity, uniformity and accuracy of the implemented correction algorithms were evaluated after the National Electrical Manufacturers Association protocol using the standard acquisition parameters. The transaxial resolution in the two-dimensional mode is 4.3 mm (4.4 mm) in the center and increases to 4.7 mm (4.8 mm) tangential and to 8.3 mm (8.0 mm) radial at a distance of r = 20 cm from the center. The axial slice width measured in the two-dimensional mode varies between 4.2 and 6.6 mm FWHM over the transaxial field of view. In the three-dimensional mode the average axial resolution varies between 4.1 mm FWHM in the center and 7.8 mm at r = 20 cm. The scatter fraction is 17.1% (32.5%) for a lower energy discriminator level of 350 keV. The maximum true event count rate of 263 (345) kcps was measured at an activity concentration of 142 (26.9) kBq/ml. The total system sensitivity for true events is 5.7 (27.7) cps/Bq/ml. From the uniformity measurements, we obtained a volume variance of 3.9% (5.0%) and a system variance of 1.6% (1.7%). The implemented three-dimensional scatter correction algorithm reveals very favorable properties, whereas the three-dimensional attenuation correction yields slightly inaccurate results in low- and high-density regions. The ECAT EXACT HR+ has an excellent, nearly isotropic spatial resolution, which is advantageous for brain and small animal studies. While the relatively low slice sensitivity may hamper the capability for performing fast dynamic two-dimensional studies, the scanner offers a sufficient sensitivity and count rate capacity for fully three-dimensional whole-body imaging.
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Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.
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The microPET Focus 120 scanner is a third-generation animal PET scanner dedicated to rodent imaging. Here, we report the results of scanner performance testing. A (68)Ge point source was used to measure energy resolution, which was determined for each crystal and averaged. Spatial resolution was measured using a (22)Na point source with a nominal size of 0.25 mm at the system center and various off-center positions. Absolute sensitivity without attenuation was determined by extrapolating the data measured using an (18)F line source and multiple layers of absorbers. Scatter fraction and counting rate performance were measured using 2 different cylindric phantoms simulating rat and mouse bodies. Sensitivity, scatter fraction, and noise equivalent counting rate (NECR) experiments were repeated under 4 different conditions (energy window, 250 approximately 750 keV or 350 approximately 650 keV; coincidence window, 6 or 10 ns). A performance phantom with hot-rod inserts of various sizes was scanned, and several animal studies were also performed. Energy resolution at a 511-keV photopeak was 18.3% on average. Radial, tangential, and axial resolution of images reconstructed with the Fourier rebinning (FORE) and filtered backprojection (FBP) algorithms were 1.18 (radial), 1.13 (tangential), and 1.45 mm full width at half maximum (FWHM) (axial) at center and 2.35 (radial), 1.66 (tangential), and 2.00 mm FWHM (axial) at a radial offset of 2 cm. Absolute sensitivities at transaxial and axial centers were 7.0% (250 approximately 750 keV, 10 ns), 6.7% (250 approximately 750 keV, 6 ns), 4.0% (350 approximately 650 keV, 10 ns), and 3.8% (350 approximately 650 keV, 6 ns). Scatter fractions were 15.9% (mouse phantom) and 35.0% (rat phantom) for 250 approximately 750 keV and 6 ns. Peak NECR was 869 kcps at 3,242 kBq/mL (mouse phantom) and 228 kcps at 290 kBq/mL (rat phantom) at 250 approximately 750 keV and 6 ns. Hot-rod inserts of 1.6-mm diameter were clearly identified, and animal studies illustrated the feasibility of this system for studies of whole rodents and mid-sized animal brains. The results of this independent field test showed the improved physical characteristics of the F120 scanner over the previous microPET series systems. This system will be useful for imaging studies on small rodents and brains of larger animals.
Purpose Quantitative 124I PET imaging is challenging as 124I has a complex decay scheme. In this study the performance of a Philips Gemini dual GS PET/CT system was optimized and assessed for 124I. Methods The energy window giving the maximum noise equivalent count rate (NECR) and NEMA 2001-NU2 image quality were measured. The activity concentration (AC) accuracy of images calibrated using factors from 18F and 124I decaying source measurements were investigated. Results The energy window 455–588 keV gave the maximum NECR of 9.67 kcps for 233 MBq. 124I and 18F image quality was comparable, although 124I background variability was increased. The average underestimation in AC in 124I images was 17.9 ± 2.9% for nonuniform background and 14.7 ± 2.9% for single scatter simulation (SSS) subtraction scatter correction. At 224 MBq the underestimation was 10.8 ± 11.3%, which is comparable to 7.7 ± 5.3% for 18F, but increased with decreasing activity. Conclusions The best 124I PET quantitative accuracy was achieved for the optimized energy window, using SSS scatter correction and calibration factors from decaying 124I source measurements. The quantitative accuracy for 124I was comparable to that for 18F at high activities of 224 MBq but diminishing with decreasing activity. Specific corrections for prompt γ-photons may further improve the quantitative accuracy.
The use of recovery coefficients (RCs) in (124)I PET lesion imaging is a simple method to correct the imaged activity concentration (AC) primarily for the partial-volume effect and, to a minor extent, for the prompt gamma coincidence effect. The aim of this phantom study was to experimentally investigate a number of various factors affecting the (124)I RCs. Three RC-based correction approaches were considered. These approaches differ with respect to the volume of interest (VOI) drawn, which determines the imaged AC and the RCs: a single voxel VOI containing the maximum value (maximum RC), a spherical VOI with a diameter of the scanner resolution (resolution RC) and a VOI equaling the physical object volume (isovolume RC). Measurements were performed using mainly a stand-alone PET scanner (EXACT HR(+)) and a latest-generation PET/CT scanner (BIOGRAPH mCT). The RCs were determined using a cylindrical phantom containing spheres or rotational ellipsoids and were derived from images acquired with a reference acquisition protocol. For each type of RC, the influence of the following factors on the RC was assessed: object shape, background activity spill in and iterative image reconstruction parameters. To evaluate the robustness of the RC-based correction approaches, the percentage deviation between RC-corrected and true ACs was determined from images acquired with a clinical acquisition protocol of different AC regimes. The observed results of the shape and spill-in effects were compared with simulation data derived from a convolution-based model. The study demonstrated that the shape effect was negligible and, therefore, was in agreement with theoretical expectations. In contradiction to the simulation results, the observed spill-in effect was unexpectedly small. To avoid variations in the determination of RCs due to reconstruction parameter changes, image reconstruction with a pixel length of about one-third or less of the scanner resolution and an OSEM 1 x 32 algorithm or one with somewhat higher number of effective iterations are recommended. Using the clinical acquisition protocol, the phantom study indicated that the resolution- or isovolume-based recovery-correction approaches appeared to be more appropriate to recover the ACs from patient data; however, the application of the three RC-based correction approaches to small lesions containing low ACs was, in particular, associated with large underestimations. The phantom study had several limitations, which were discussed in detail.
The positron emitters (18)F, (68)Ga, (124)I, and (89)Zr are all relevant in small-animal PET. Each of these radionuclides has different positron energies and ranges and a different fraction of single photons emitted. Average positron ranges larger than the intrinsic spatial resolution of the scanner (for (124)I and (68)Ga) will deteriorate the effective spatial resolution and activity recovery coefficient (RC) for small lesions or phantom structures. The presence of single photons (for (124)I and (89)Zr) could increase image noise and spillover ratios (SORs). Image noise, expressed as percentage SD in a uniform region (%SD), RC, and SOR (in air and water) were determined using the NEMA NU 4 small-animal image-quality phantom filled with 3.7 MBq of total activity of (18)F, (68)Ga, (124)I, or (89)Zr. Filtered backprojection (FBP), ordered-subset expectation maximization in 2 dimensions, and maximum a posteriori (MAP) reconstructions were compared. In addition to the NEMA NU 4 image-quality parameters, spatial resolutions were determined using small glass capillaries filled with these radionuclides in a water environment. The %SD for (18)F, (68)Ga, (124)I, and (89)Zr using FBP was 6.27, 6.40, 6.74, and 5.83, respectively. The respective RCs were 0.21, 0.11, 0.12, and 0.19 for the 1-mm-diameter rod and 0.97, 0.65, 0.64, and 0.88 for the 5-mm-diameter rod. SORs in air were 0.01, 0.03, 0.04, and 0.01, respectively, and in water 0.02, 0.10, 0.13, and 0.02. Other reconstruction algorithms gave similar differences between the radionuclides. MAP produced the highest RCs. For the glass capillaries using FBP, the full widths at half maximum for (18)F, (68)Ga, (124)I, and (89)Zr were 1.81, 2.46, 2.38, and 1.99 mm, respectively. The corresponding full widths at tenth maximum were 3.57, 6.52, 5.87, and 4.01 mm. With the intrinsic spatial resolution (approximately 1.5 mm) of this latest-generation small-animal PET scanner, the finite positron range has become the limiting factor for the overall spatial resolution and activity recovery in small structures imaged with (124)I and (68)Ga. The presence of single photons had only a limited effect on the image noise. MAP, as compared with the other reconstruction algorithms, increased RC and decreased %SD and SOR.
The key performance measures of resolution, count rate, sensitivity and scatter fraction are predicted for a dedicated BGO block detector patient PET scanner (GE Advance) in 2D mode for imaging with the non-pure positron-emitting radionuclides 124I, 55Co, 61Cu, 62Cu, 64Cu and 76Br. Model calculations including parameters of the scanner, decay characteristics of the radionuclides and measured parameters in imaging the pure positron-emitter 18F are used to predict performance according to the National Electrical Manufacturers Association (NEMA) NU 2-1994 criteria. Predictions are tested with measurements made using 124I and show that, in comparison with 18F, resolution degrades by 1.2 mm radially and tangentially throughout the field-of-view (prediction: 1.2 mm), count-rate performance reduces considerably and in close accordance with calculations, sensitivity decreases to 23.4% of that with 18F (prediction: 22.9%) and measured scatter fraction increases from 10.0% to 14.5% (prediction: 14.7%). Model predictions are expected to be equally accurate for other radionuclides and may be extended to similar scanners. Although performance is worse with 124I than 18F, imaging is not precluded in 2D mode. The viability of 124I imaging and performance in a clinical context compared with 18F is illustrated with images of a patient with recurrent thyroid cancer acquired using both [124I]-sodium iodide and [18F]-2-fluoro-2-deoxyglucose.
To evaluate the performance of the positron emission tomography (PET)/computed tomography (CT) Discovery-STE (D-STE) scanner for lesion detectability in two-dimensional (2D) and three-dimensional (3D) acquisition. A NEMA 2001 Image-Quality phantom with 11 lesions (7-37 mm in diameter) filled with a solution of 18F (lesion/background concentration ratio: 4.4) was studied. 2D and 3D PET scans were sequentially acquired (10 min each) in list mode (LM). Each scan was unlisted into 4, 3 and 2-min scans. Ten [18F]FDG PET oncological patient studies were also evaluated. Each patient underwent a 3D PET/CT whole body scan, followed by a 2D PET scan (4 min LM) and a 3D PET scan (4 min LM) over a single field of view. Both 2D and 3D scans were unlisted in 3 and 2-min scans. Data were evaluated quantitatively by calculating quality measurements and qualitatively by two physicians who judged lesion detectability compared to statistical variations in background activity. Quantitative and qualitative evaluations showed the superiority of 3D over 2D across all measures of quality. In particular, lesion detectability was better in 3D than in 2D at equal scan times and 3D acquisition provided images comparable in quality to 2D in approximately half the time. Interobserver variability was lower in evaluation of 3D scans and lesion shape and volume were better depicted. In oncological applications, the D-STE system demonstrated good performance in 2D and 3D acquisition, while 3D exhibited better image quality, data accuracy and consistency of lesion detectability, resulting in shorter scan times and higher patient throughput.