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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5668_Библиотеки_им_академика_М_И_Перельмана
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5 18F-NaF
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Fig. 5.3 Whole body PET maximum intensity projection
of the physiological
18
F-NaF bio-distribution
is evident a lower gradient of uptake in the appendicular skeleton (Fig.5.3). Due to the renal excretion, kidneys, ureters and bladder are normally
visualized, with some inter-individual variability.
The 18F-NaF distribution in soft tissues and
parenchymatous organs is negligible [
5]. Extra-
osseous calcications can show 18F-NaF uptake,
as for calcium deposits in large arteries [6].
5.4 Clinical Indications
5.4.1 Bone Metastases
For the reasons expressed above, PET/CT with
18
F-NaF shows high sensitivity in the identication of bone metastases. The diagnostic accuracy
is higher for sclerotic lesions rather than lytic
ones [7]. Therefore, the main eld of applications
of this tracer is the diagnosis of bone metastases
93
from prostate cancer, lung carcinoma, and mixed
bony lesions of breast cancer.
In breast, prostate, and lung cancer patients,
several studies have been elucidated a sensitivity
18
of 100% for
F-NaF PET/CT in the diagnosis of
bone metastases, also superior to bone scan with
99m
Tc-MDP and/or PET/CT with 18F-FDG [8].
Regarding conventional bone scan, planar imaging often cannot provide meaningful information
about lesion detection or anatomical localization
and must be supplemented with SPECT or
SPECT/CT to increase the diagnostic accuracy.
Conversely, 18F-NaF PET/CT displays greater
spatial resolution and better image quality in a
shorter acquisition time, resulting in higher sensitivity [9]. Moreover, the CT component of the
exam can accurately depict morphologic features
of lesions, allowing a better specicity than planar bone scan. On this topic, we must also consider the larger availability of hybrid PET/CT
rather than SPECT/CT scanners.
PET/CT with 18F-NaF shows superior diagnostic accuracy in detection of bone metastases,
also in comparison with other radiopharmaceuticals, as radiolabeled choline in prostate cancer
patients [10, 11]: in particular, it is known that, in
patients undergoing anti-androgenic therapy,
prostate cancer sclerotic lesions can occasionally
show faint radiolabeled choline uptake [12],
while this feature is not known for 18F-NaF.
Despite a better sensitivity of 18F-NaF in detecting bone metastases, in comparison with the most
widely used PET tracers as
18
F-FDG and (11C-18F)choline, a limit of this tracer is also the inadequacy
to depict other ndings beyond osseous lesions. In
fact, 18F-FDG PET/CT allows to evaluate in a single session soft tissues, parenchymatous organs,
and bone involvement in patients with high grade
of glucose metabolism tumors, while radiolabeled
choline simultaneously evaluates bone involvement, lymph nodal metastases, and local relapse in
prostate cancer patients. Therefore, the right
moment to perform 18F-NaF PET/CT is a matter of
discussion. Standing to the current guidelines of
the European Association of Nuclear Medicine
and Molecular Imaging (EANM), 18F-NaF PET/
CT can be considered as a valid tool in the evalua-
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tion of primary bone malignancies such as osteosarcoma [13], in the assessment of metastatic bone
disease and in evaluation of abnormal radiographic
or laboratory ndings [14].
In a recent study, 130 patients with suspicion
of bone metastases were examined with 18F-NaF
PET/CT: in the large majority of these patients
(114/130; 87.7%), at least an extra-skeletal
abnormal nding was recorded on the CT component of the studies. In the population were
recorded cases of intracranial hemorrhage,
pneumothorax, pulmonary brosis, pericardial
effusion, emphysema and pulmonary, hepatic
and lymph nodal secondary lesions [15]. Thus,
in the clinical practice of nuclear medicine physicians with 18F-NaF PET/CT, it is important to
achieve a good skill on the CT component of the
exam in order to improve condence in the differential diagnosis between secondary bone
lesions and false positive cases of 18F-NaF
uptake in the bones and, in second instance, to
globally evaluate extra-skeletal pathologic ndings which can be observed at the CT and can
occur in a signicant minority of the examined
patients (5%) [15].
As a future trend, several studies are demonstrating the usefulness of 18F-NaF PET/CT in the
follow-up of castration resistant prostate cancer
with skeletal metastases and in the evaluation of
response to therapy with
223
Ra-dichloride (see
also Chap. 10) [16, 17].
5.4.2 Benign Bone Disease
During the time, due to the specific affinity of
18
F-NaF for the skeletal system, a feasible role
of this tracer in the management of bony
benign lesions has been hypothesized. Several
studies proposed the 18F-NaF as a feasible
agent in the depiction of bone degenerative or
inflammatory diseases and in the evaluation of
disease progression, as for spondylo-arthropathy in psoriatic arthritis [
18], ankylosing spon-
dylitis [19], avascular osteonecrosis [20], and
Paget’s disease [21].
Other studies focused the attention on orthopedic diseases as spondylolysis and spondylolisthesis and painful prosthetic joints [22, 23].
Naturally, in benign bone diseases, the physiological processes of bone remodeling are at the
basis of tracer uptake. Anyway, the cited clinical indications are related to few studies or
reports of a case. A strict collaboration between
nuclear medicine physicians and clinicians as
orthopedics specialists or rheumatologists
should be recommended in order to avoid not
useful scans, to verify clinical benet, and to
select patients who can really take advantage
by a PET/CT with 18F-NaF.
As a future trends, initial reports are suggesting a feasible role of 18F-NaF PET/CT in the
evaluation of osteoid-osteoma in pediatric
patients and in the sports medicine [24].
5.4.3 Forensic Use
Due to the extreme versatility of this tracer as a
marker of bone metabolism, recent studies are
suggesting its possible role as a PET tracer for
forensic use, due to the accurate diagnosis of
injuries in cases of child abuse, especially when
injuries are not associated with radiographically
evident fractures [
graphic skeletal survey is the main diagnostic
technique used for imaging suspected infant
abuse, and the role of nuclear medicine is less
well established. The 18F-NaF PET/CT can
potentially allow to detect the presence of bone
fractures or injuries not evident on skeletal radiographic surveys [26].
25]. In practice, the radio-
de
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5.5 Clinical Cases (Figs.5.4, 5.5,
5.6, 5.7, 5.8, and5.9)
abc
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Fig. 5.4 In patient previously treated for breast cancer
and submitted to radiotherapy for bone metastases in the
lumbar spine, the whole body
displays diffuse tracer uptake in the lumbar tract of the
spine and in correspondence of arthrosis in both knees.
The whole body 3D, PET maximum intensity projection
99m
Tc-MDP bone scan (a)
18
F-NaF (b) better shows the uptake in the lumbar
with
vertebrae, in association with vertebral, metastatic sclerotic lesions in sagittal CT (c) and PET/CT (d) views. In
the sagittal PET/CT view is also evident a further lesion,
misdiagnosed at bone scan, in the spinous process of the
epistropheus
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ab c
b
1
b
2
b
3
b
4
b
5
F. Calabria et al.
c
1
c
1
Fig. 5.5 In a patient examined for early biochemical
relapse of prostate cancer (PSA 1.4 ng/ml) 2 years following radical prostatectomy, the whole body
99m
Tc-MDP
bone scan (a) shows a single area of focal uptake in the
right pubic bone, suspicion for secondary. Instead, the
whole body 3D, PET maximum intensity projection with
18
F-NaF (b) displays multiple sites of pathologic tracer
uptake, in the atlas, right scapula, several vertebrae, ribs,
d
b
6
18
sacrum, and right ileum, evident in
views (b
18
F-choline PET/CT (c), conrming as 18F-choline avid
). The same patient also undergone
1–b6
only two lesions, respectively, localized in the 2nd right
) and in the right ileum (c2). Interestingly, only the
rib (c
1
18
F-choline avid lesions were also associated with
two
sclerotic lesions on the CT (d)
F-NaF PET/CT
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ab
a
1
b
1
def
c
Fig. 5.6 A 64-year-old woman, previously submitted to
surgery and chemotherapy for breast cancer, was examined with both
3D PET maximum intensity projection and axial
PET/CT (a, a
hemithorax.
18
F-FDG and 18F-NaF PET/CT. 18F-FDG
) show focal uptake in two ribs in the right
1
18
F-NaF 3D PET maximum intensity projec-
18
F-FDG
tion (b) shows morel lesions in the right hemithorax and
pathologic uptake in some vertebrae of the dorsal spinal
tract, also evident in
18
F-FDG PET/CT view of the spine (d) does not show sig-
nicant ndings, while the sagittal
18
F-NaF axial PET/CT (b1). Sagittal
18
F-NaF PET/CT (e)
view displays focal uptake in the 8th dorsal vertebra, in
association with sclerotic lesion on the CT component of
the exam (f, c)
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ac
a’
a”
Fig. 5.7 A 70-year-old patient examined by PET/CT
with double tracers (
restaging of prostate cancer, 8 months after radical prostatectomy, due to biochemical relapse (PSA = 0.6 ng/mL).
18
F-choline PET maximum intensity projection (a) does
not show any site of disease relapse. In particular, no
pathologic tracer uptake is detectable in the 10th left rib
and in the 3rd right rib in axial PET/CT details (a′, arrow,
a″, curved arrow). Moreover, no signicant morphologi-
18
F-choline and 18F-NaF) during
b
b’
c’
c”
cal abnormalities are observed at correlative CT views (b,
arrow, b′, curved arrow). Nevertheless,
mum intensity projection (c) shows several sites bony
lesions, respectively, in the right clavicula, in the 4th cervical vertebra, in some ribs, and in the sacrum. In particular, axial PET/CT details display pathologic
uptake in the 10th left rib and in the 3rd right rib (c′,
arrow, c″, curved arrow)
18
F-NaF maxi-
18
F-NaF
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ab
c d
Fig. 5.8 18F-Choline PET/CT and 18F-NaF PET/CT per-
formed in the same patient, during biochemical relapse of
prostate cancer.
jection (a) single area of abnormal uptake in the pelvis,
18
while
allows to detect several foci of pathologic tracer uptake in
the skeleton. Axial
pathologic tracer uptake in an 8mm wide pelvic lymph
18
F-Choline PET maximum intensity pro-
F-NaF PET maximum intensity projection (b)
18
F-choline PET/CT detail (c) displays
e
f
g
node, also evident in correlative CT view (d). No
18
F-choline uptake can be documented in sclerotic lesions
in the left ileum and ipsilateral femur, while these ndings
are clearly
18
F-choline PET/CT (e), CT (f), and 18F-NaF PET/CT (g)
views of the left ileum and axial
CT (i) and
18
F-NaF avid, as summarized in axial
18
F-NaF PET/CT (j) views of the left femur
h
i
j
18
F-choline PET/CT (h),
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ab
F. Calabria et al.
Fig. 5.9 A 72-year-old patient examined by means of
18
F-choline PET/CT and 18F-NaF PET/CT due to biochemical relapse of prostate cancer.
imum intensity projection (a) does not show sites of
disease relapse.
18
F-NaF PET maximum intensity projec-
18
F-choline PET max-
5.6 PET/CT Acquisition Protocols
Whole body PET/CT: from the vertex of the skull
to the feet. The arms may be by the sides for
whole body imaging. No fasting or special patient
preparation is needed for 18F-NaF PET/CT.Only
oral hydration is suggested to obtain a faster renal
excretion and to optimize radiation exposure.
The dose (185–370 MBq) should be administered as a bolus through a catheter inserted into a
large peripheral vein. The whole body imaging
starts 45–60min after the injection (2–5min per
bed position, depending on the PET scanner). A
low dose CT (90 mA) is sufcient for the anatomical localization of bone ndings. Being the
exam focused on the skeleton, routinely iodinate
CT contrast media administration is not necessary [
27].
Similar to 18F-FDG PET/CT, maximum inten-
sity projection (MIP) images should be generated
to facilitate lesion detection.
e
tion (b) shows several bony localizations. Axial details of
both scans allow to detect osseous lesions of the 4th right
rib and ipsilateral femur, not showing
(c, d), with sclerotic margins at CT (e, f) and intense
NaF uptake (g, h)
f
18
F-choline uptake
18
F-
5.7 Variants andPitfalls
An important limit of 18F-NaF in metastatic disease evaluation is the inherent mechanism of
tracer uptake, not specic for tumor but primarily
marker of an osteoblastic response. Therefore, it
is important to consider the uptake in benign
lesions, which can simulate malignant diseases.
Normally, the most common site of physiopathological uptake is represented by the osteoarthritis [28]. Nuclear medicine physicians must take
into account this feature when approaching 18F-NaF
PET/CT for metastatic bone disease evaluation. The
optimal knowledge of diagnostic CT criteria helps
in this panorama. However, the high sensitivity of
this tracer allows disease detection before the evidence of morphological lesions that can be radiologically observed. Therefore, the accurate
collection of anamnestic data (in particular for
trauma and bone pain) and a holistic clinical
approach to the scan are recommended (Fig.5.10).
ef
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ab
101
c
d
Fig. 5.10 A patient with early biochemical relapse of
prostate cancer (PSA 0.8 ng/ml) after radical prostatectomy was examined by means of
18
F-choline PET/CT.The whole body, 3D, 18F-NaF PET
maximum intensity projection and axial PET view (b)
show a single area of focal tracer uptake in the right
ischium, in association with geodic lesion, evident in corresponding CT (c) and PET/CT (d) views. The whole
18
F-NaF uptake is frequent in osteoarthritis, as
18
F-NaF PET/CT and
well as for rheumatoid arthritis [29] and inammation [30]. It has also been considered a possible application of this radiopharmaceutical in the
evaluation of atheromatous plaques and in the
study of calcic plaque versus the vulnerable
carotid atheroma [
31] or in study connection
between atherosclerotic plaque and trabecular
bone degeneration [32].
A possible role of 18F-NaF PET/CT has been
hypothesized in the diagnosis and monitoring of
osteoporosis. Currently, osteoporosis and other
metabolic bone diseases are evaluated primarily
through X-rays; 18F-NaF PET/CT can provide a
molecular perspective with respect to the underlying metabolic alterations that lead to osseous
disorders, by measuring bone turnover through
standardized uptake value (SUV). Its sensitivity
and ability to examine the entire skeletal system
g
h
18
F-choline PET maximum intensity projection (e)
body
and relative axial
(f–h) conrm as
serum level, the peri-articular site of the uptake, and the
hypodensity of the lesion were not congruous with a secondary prostate cancer metastasis. The ndings of both
tracers were considered as false positive in a site of arthrosis. This suspicion was conrmed at clinical follow-up
18
F-choline PET, CT, and PET/CT views
18
F-choline-avid lesion. The low PSA
support its superior imaging quality compared to
standard structural imaging techniques [
33].
However, further studies are needed to assess its
accuracy in depicting the efcacy of therapy.
Conversely, PET/MRI is enlarging the eld of
potential applications of 18F-NaF to nononcologic musculoskeletal disorders, including
inammatory and infectious conditions and postoperative complications. There is great potential
for an increased role for 18F-NaF to serve as a
primary or complementary modality in the management of orthopedic and rheumatologic disorders, as osteomyelitis, polymyalgia rheumatica,
rheumatoid arthritis, septic arthritis. Some further benign conditions may be observed as 18FNaF PET/CT scans performed for oncologic
purpose, as enchondromatosis (Fig. 5.11) and
enthesopathy (Fig. 5.12); these benign lesions
may represent a source of false positive ndings
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F. Calabria et al.
c
d
Fig. 5.11 A 59-year old patient was examined by means
18
F-NaF PET/CT for biochemical recurrence of pros-
of
tate cancer, three years after radical prostatectomy; PSA
was 0.2 ng/mL at the time of the scan. PET maximum
intensity projection (a) shows single area of intense tracer
uptake in the 10th rib of the right hemithorax. No pain at
the chest region was reported. Axial CT (b), PET/CT (c)
views and coronal CT detail (d, arrow) show a lesion with
ab
sharply dened scalloped margins, without periosteal
reaction. The lesion was highly suspicious for enchondroma. CT volume rendering (e) and PET volume rendering (f), respectively, display the lesion of the 10th rib with
moderate expansion of the overlying cortex uptake and
the uptake, superior to osseous background. The diagnosis
was conrmed at follow-up
Fig. 5.12 Whole body
NaF PET/CT performed in the same patient, during fol-
up of prostate cancer. Anterior view of
low(a) did not show sites of osseous disease relapse. Due to
the better power resolution limit,
played two sites of abnormal uptake, respectively, in the
11th left rib and in the ipsilateral femur. Axial PET/CT
99m
Tc-MDP bone scan and 18F-
99m
Tc-MDP
18
F-NaF PET/CT (b) dis-
and CT details (c, d, e, f, curved arrow) allow to exclude
morphological abnormalities of the 11th left rib and to
detect the uptake on the femur as due to enthesopathy.
Patient also referred post-traumatic pain in the left hemithorax; the uptake was due to regenerative process after
injury. Post-traumatic injuries and enthesopathy may lead
to false positive ndings at
18
F-NaF PET/CT imaging
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