Dr. Williams is an Assistant Professor at the Department of
Pediatric Radiology, Texas Children’s Hospital, Baylor College of
Medicine, Houston TX; and Dr. Treves is a Professor of Radiology
(Nuclear Medicine) Division of Nuclear Medicine and Molecular Imaging,
Department of Radiology, and the Director of the Joint Program in
Nuclear Medicine, Harvard Medical School, Children’s Hospital Boston,
Positron emission tomography (PET) imaging of the
pediatric patient is being performed with increasing frequency. The
common pediatric adage stating that children are not simply little
adults holds particularly true with regard to PET imaging. One of the
primary differences between pediatric and adult imaging is the
underlying pathology being evaluated. While some neoplastic entities are
common in children and adults (primarily lymphoma), many are unique to
children. Children also have variants of fludeoxyglucose (FDG) uptake
that must be known to correctly interpret studies. Patient preparation
and radiation dosage are further variables that differ between children
This paper addresses the unique circumstances involved
in PET imaging of children. Patient preparation and image acquisition
will be discussed briefly. Normal findings will be reviewed and followed
by an overview of the more common uses of PET in children. We presenta
particular focus on oncologic, brain, and bone imaging, along with an
up-to-date discussion on evolving trends. Finally, we will present
abrief overview of some of the more rare indications for PET
Preparation for pediatric PET
imaging begins well before the actual image acquisition. As in the case
of adults, glucose levels are checked prior to FDG administration;
levels should be under 150 ng/dL.1 Elevated glucose results
in increased insulin release and subsequent muscular FDG uptake.
Moreover, in patients with elevated intrinsic glucose levels, native
glucose will compete with the radiolabeled glucose, and potentially
result in a false negative exam.2 Fasting prior to PET
examination is required, and parents are instructed not to feed their
children for 4 hours prior to the test. Infants should also fast for 4
hours, but they can be breast- or bottle-fed shortly after radiotracer
Brown fat, while not unique to children, is visualized
much more frequently in children than in adults. When FDG uptake is
particularly prominent, brown fat can obscure true pathology and make
image interpretation difficult. Medications, such as propanolol or
fentanyl, have been used to decrease brown fat uptake; however,
drug-free methods are also effective. Studies have shown that patients
kept in a room witha constant temperature of 24 C for 30 min prior to
radiotracer injection and 1 hour following injection, had minimal brown
fat uptake.3 This procedure is recommended for children as it
minimizes brown fat uptake and eliminates the adverse effects of the
Patient cooperation can sometimes be
challenging even in adults; thus, the thought of coercing a young child
to lie still for an extended time for PET imaging raises obvious
concerns. While sedation is utilized more frequently in children, the
associated anesthesia risks cannot be ignored. Techniques to minimize
patient anxiety can often result in superb image acquisition without
anesthesia. Child-friendly rooms and technologists with pediatric
experience greatly help to minimize anxiety. Evaluating each child with
regard to sedation needs is recommended rather than employing a strict
age requirement for sedation.1,2
pediatric PET exams requires an understanding of normal variants present
in children. One of the most confusing areas of potentially normal
uptake is the thymus. Normal uptake in the thymus can be detected into
adolescence. Differentiating this uptake from neoplastic involvement can
be difficult, however, evaluating the shape of the thymus (normally an
inverted V) and degree of uptake can be helpful (Figure 1). Tonsillar
uptake can frequently be seen in children, and can result in a
diagnostic dilemma in lymphoma patients. Benign uptake within the
tonsils is typically symmetric; lymphomatous involvement is usually
irregular/asymmetric. Brown adipose uptake is common in children, and
knowing its distribution is critical for image interpretation (Figure
2).4 Visualization of uptake in the cervical cords is common, especially if the child talks or cries after FDG injection.
As is the case with adults, the most
common use of PET in children is oncologic imaging. PET has many uses in
tumor evaluation, including initial staging, evaluating therapy
response and disease recurrence, and aiding in therapy planning.5
Occasionally, PET is used to evaluate tumors with atypical behavior.
For instance, PET has been found useful in evaluating
metaiodobenzylguanidine (MIBG) negative neuroblastoma6,7 or radioiodine-negative thyroid carcinomas.8 Another rare use of PET is to search for occult malignancy.
The most frequently imaged neoplasm in the child is lymphoma.9 Pediatric lymphoma is a highly curable disease,10
but determining disease extent is critical to proper therapy. PET is
used for initial staging and frequently repeated following a short
interval to ensure that an appropriate response to chemotherapy has
occurred (Figure 3). This allows for rapid therapy alterations in
children not demonstrating a robust response, and for improvement in
Sarcomas are also frequently imaged in children.
Rhabdomyosarcoma is the most frequent soft-tissue malignancy in
children. While it arises from all cells in the body, excluding only the
brain parenchyma, in children it most commonly arises from the
genitourinary tract and muscular system. PET is extremely useful in
evaluating the extent of disease in these patients (Figure 4). PET can sometimes better demonstrate disease extent in osteosarcoma and Ewing’s sarcoma as well. (Figure 5).11
has been used to evaluate other rare pediatric neoplasms, including
central nervous system neoplasms (discussed below), post-transplant
lymphoproliferative disorder (PTLD) (Figure 6) leukemia, Wilm’s tumor,
hepatoblastoma, retinoblastoma, and neurofibromatosis/nerve sheath
tumors (Figure 7). Continued research in specific pediatric
tumors is needed to evaluate PET’s efficacy in these malignancies.For
instance, PET evaluation in adult patients with neurofibromatosis type I
is beneficial in differentiating between malignant and nonmalignant
neoplasms in adults.12 Essentially, any FDG-avid neoplasm can
be imaged with PET; however, clinical investigation is necessary to
determine its appropriate use in children.
While FDG is, by far,
the most commonly employed radiopharmaceutical used in tumor evaluation,
other agents are available. F-18 sodium fluoride is useful in imaging
skeletal sarcomas (see bone section below). Radiolabeled amino acids,
such as C-11 methionine and F-18 fluorothymidine,13,14 are
being investigated for brain tumor evaluation secondary to their
significant improvement in targeting to background ratio. With continued
research, additional agents will likely be available in the future.
18F-labeled sodium fluoride
(NaF) was initially introduced in the early 1960’s. It was infrequently
used, however,secondary due to the technical limitations of imaging 511
kEv photons with a gamma camera, as well as to the difficulty with
radiotracer preservation.15 The development of PET imaging in the early 1990’s has resulted in a resurrection in NaF use.16 Several
studies have reported improved detection of both benign and malignant
bone lesions with NaF PET compared to technetium methylene
diphosphonate(TcMDP), although most of these were performed on adults.
Importantly, the dosimetry of NaF PET is similar to that of the MDP bone
18F-labeled NaF is useful in the evaluation of back pain.16,17
Spondylolysis is a common cause of back pain in children, and PET
imaging can produce detailed images of a pars defect (Figure 8). In
general, NaF PET has been shown to have increased sensitivity in lesion
detection with radiation doses similar to those of MDP bone scans. NaF
has been shown to have particular benefit in the evaluation of child
abuse.Recent studies have shown NaF PET to have improved sensitivity in
detection of all fractures except classic metaphyseal lesions.18
It is particularly useful in early detection of posterior rib fractures
(Figure 9). Often NaF PET can be used to supplement a skeletal survey
in questionable cases. As research continues, growing acceptance of this
agent and its increased utilization for various pathologies is likely.
PET is highly useful in pediatric
neuroimaging, primarily in seizure evaluation. There are multiple
etiologies to be considered in the child or infant presenting with a
seizure: infantile spasms, structural abnormalities (ie, cortical
dysplasia), tuberous sclerosis/phakamotsis, metabolic conditions,
trauma, and neoplasms, to name a few. When routine medical and imaging
evaluation does not provide answers, further investigation with PET
imaging, and typically single photon emission computed tomography
(SPECT), is often employed.
PET of the brain is performed on
patients with seizure disorders during the interictal phase, and it has
been found to be more sensitive in lesion detection versus interictal
SPECT. Regions of decreased FDG uptake on interictal exams correlate to
seizure foci (Figure 10).19 PET and magnetic resonance
imaging (MRI) fusion is particularly useful in localizing a lesion, and
when fusion software is available, multiple modalities can be summed to
best localize a lesion.
The other main indication for PET in
brain imaging is in tumor evaluation. FDG uptake in neoplasms can be
difficult to evaluate secondary to extensive normal background uptake in
the brain. Some neoplasms demonstrate marked FDG avidity, and can be
easily visualized on PET (Figure 11).20 PET can be beneficial
in differentiating between residual tumor and radiation necrosis. Amino
acid-labeled agents have shown promise for improved brain parenchyma
imaging as there is minimal background uptake in normal brain obscuring
neoplastic uptake (Figure 12).13,14
PET imaging in children is continuously
evolving. It is being used to evaluate new pathologies, such as LCH,
moyamoya, and fibromyxoid tumors. New radiopharmaceuticals are being
developed and will likely provide clinical benefits in the future.
Moreover, the fundamental technology is on the verge of advancing with
PET/MR availability approaching the clinical arena. The future of PET
imaging in children will undoubtedly continue to advance, and with this
comes an exciting opportunity for the interpreting physician.
- McQuattie S. Pediatric PET/CT imaging: Tips and techniques. J Nucl Med Technol. 2008;36:171-178.
- Roberts EG, Shulkin BL. Technical issues in performing PET studies in pediatric patients. J Nucl Med Technol. 2004;32:5-9; quiz 10–1.
KA, Fahey FH, Laffin S, et al. Seasonal variation in the effect of
constant ambient temperature of 24°C in reducing FDG uptake by brown
adipose tissue in children. Eur. J. Nucl. Med. Mol. Imaging. 2010;37:1854-1860.
- Shammas A, Lim R, Charron M. Pediatric FDG PET/CT: Physiologic uptake, normal variants, and benign conditions. Radiographics. 2009;29:1467-1486.
- Chen Z, Li X, Li F, et al. Evolving role of 18F-FDG-PET/CT for the body tumor and metastases in pediatrics. Euro J Radiol. 2010;75:329-335.
- Sharp SE, Shulkin BL, Gelfand MJ, et al. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009;50:1237-1243.
DR, Han MM, Quach A, et al. Comparison of iodine-123
metaiodobenzylguanidine (MIBG) scan and [18F] fluorodeoxyglucose
positron emission tomography to evaluate response after iodine-131 MIBG
therapy for relapsed neuroblastoma. J Clin Oncol. 2009;27:5343-5349.
B, Bohuslavizki KH, Beyer W, et al. Impact of FDG PET on patients with
differentiated thyroid cancer who present with elevated thyroglobulin
and negative 131I scan. J Nucl Med. 2001;42:71-76.
- Stauss J, Franzius C, Pfluger T, et al. Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology. Eur. J. Nucl. Med. Mol. Imaging. 2008;35:1581-1588.
- Hudson MM, Krasin MJ, Kaste SC. PET imaging in pediatric Hodgkin’s lymphoma. Pediatr Radiol. 2004;34:190-198.
- McCarville MB, Christie R, Daw NC, et al. PET/CT in the evaluation of childhood sarcomas. AJR Am J Roentgenol. 2005;184:1293-1304.
- Bredella MA, Torriani M, Hornicek F, et al. Value of PET in the assessment of patients with neurofibromatosis type 1. AJR Am J Roentgenol. 2007;189:928-935.
AH, Thomas A, Kracht LW, et al. 18F-fluoro-L-thymidine and
11C-methylmethionine as markers of increased transport and proliferation
in brain tumors. J. Nucl. Med. 2005;46: 1948-1958.
- Rueger MA, Ameli M, Li H, et al. [18F]FLT PET for non-invasive
monitoring of early response to gene therapy in experimental gliomas. Mol Imaging Biol. 2010;13:547–557.
- Grant FD, Fahey FH, Packard AB, et al. Skeletal PET with 18F-fluoride: Applying new technology to an old tracer. J Nucl Med. 2007;49:68-78.
R, Fahey FH, Drubach LA, et al. Early experience with fluorine-18
sodium fluoride bone PET in young patients with back pain. J Pediatr Orthop. 2007;27:277-282.
D, Metser U, Lievshitz G., et al. Back pain in adolescents: assessment
with integrated 18F-fluoride positron-emission tomography-computed
tomography. J Pediatr Orthop. 2007;27:90-93.
- Drubach LA, Sapp MV, Laffin S, Kleinman PK. Fluorine-18 NaF PET imaging of child abuse. Pediatr Radiol. 2008;38:776-779.
- Sood S, Chugani HT. Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy. Childs Nerv Syst. 2006;22:810-820.
- Kim S, Salamon N, Jackson HA, et al. PET imaging in pediatric neuroradiology: Current and future applications. Pediatr Radiol. 2010;40:82-96.