Multimodality molecular imaging combines multiple imaging modalities to provide enhanced visualization of biological processes. Positron emission tomography (PET) is particularly useful for molecular imaging as it can radiolabel biological molecules to image specific targets or pathways. PET combined with computed tomography (CT) or magnetic resonance imaging (MRI) provides highly accurate anatomical and functional information by precisely aligning PET and anatomical images. These hybrid PET/CT and PET/MRI systems utilize the strengths of each modality and offer opportunities to study molecular biology and disease in novel ways.

1. MULTIMODALITY MOLECULAR IMAGING – AN OVERVIEW WITH
SPECIAL FOCUS ON PET/CT

2. Review Article
Molecular imaging originated from the field of radio
pharmacology due to the need to better understand the
fundamental molecular pathways inside organisms in a
noninvasive manner. It is defined as “the visual
representation, characterization, and quantification of
biological processes at the cellular and sub-cellular levels
within intact living organisms” [1]. It enables the
visualizationofthecellularfunctionandthefollow-upofthe
molecular process in living organisms without perturbing
them.Molecularimagingdiffersfromtraditionalimagingin
that probes known as biomarkers are used to help image
particular targets or pathways. Biomarkers interact
chemically with their surroundings and in turn alter the
image according to molecular changes occurring within the
area of interest. This process is markedly different from
previous methods of imaging which primarily imaged
differencesinqualitiessuchasdensityorwatercontent.This
ability to image fine molecular changes opens up an
incredible number of exciting possibilities for medical
application, including early detection and treatment of
disease and basic pharmaceutical development. Further-
more, molecular imaging allows for quantitative tests,
impartingagreaterdegreeofobjectivitytothestudyofthese
areas. Many areas of research are being conducted in the
field of molecular imaging. Much research is currently
centered on detecting what is known as a predisease state or
molecular states that occur before typical symptoms of a
disease are detected. Other important veins of research are
the imaging of gene expression and the development of
novel biomarkers. Recently the term “Molecular Imaging”
has been applied to a variety of microscopy and nanoscopy
techniques including live-cell microscopy.There are many
different modalities that can be used for noninvasive
molecular imaging. Each has their different strengths and
weaknesses and some are more adept at imaging multiple
targets than others. PET has a special place. Many
biological molecules could be radio-labeled and become
PET tracers. Figure 1 depicts grossly the extent of each
imaging modality based on its widespread use [2].
Multimodality imaging has emerged as a technology
that utilizes the strengths of different modalities and yields
ahybridimagingplatformwithbenefitssuperiortothoseof
MULTIMODALITY MOLECULAR IMAGING –AN OVERVIEW WITH
SPECIAL FOCUS ON PET/CT
N Savita*, Sudeshna Maitra* and Uma Ravishankar**
*Registrar, **Senior Consultant Department of Nuclear Medicine, Indraprastha Apollo Hospitals, Sarita Vihar,
New Delhi 110 076, India.
Correspondence to: Dr.Uma Ravishankar, Senior Consultant,Department of Nuclear Medicine,
Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
E-mail: uma_r@apollohospitals.com
Imaging capabilities have evolved from those that provide anatomical pictures to those that capture functional
information and, more recently, molecular information (nuclear medicine, PET, SPECT, PET/CT, SPECT/CT,
MRS, contrast-enhanced ultrasound, fluorescence and bioluminescence imaging). Multimodality imaging has
emerged as a technology that utilizes the strengths of different modalities and yields a hybrid imaging platform
with benefits superior to those of any of its individual components, considered alone. Leading edge hybrid
imaging (combining multiple, complementary imaging technologies such as PET and CT) offer unique
opportunities to “view” the molecular biology of disease, and the use of this equipment is on the rise.
Key words: Multimodality imaging; PET/CT; PET/MRI; SP.
Fig.1 Extent, over the imaging applications, of the most
popular medical imaging modalities based on their
widespread use [2].
Apollo Medicine, Vol. 7, No. 3, September 2010 190

3. Review Article
191 Apollo Medicine, Vol. 7, No. 3, September 2010
any of its individual components, considered alone.
Molecular imaging, by definition, renders information that
can not be provided by conventional radiological imaging,
but regardless needs integration of anatomy and function to
be fully understood.
POSITRON EMISSION TOMOGRAPHY (PET)
COMBINED WITH OTHER MODALITIES
Principle of PET scanner
Positron emission tomography (PET) is a tomographic
technique that computes the three-dimensional distribution
of radioactivity based on the annihilation photons that are
emittedbypositronemitterlabeledradiotracers.PETallows
non-invasive quantitative assessment of biochemical and
functional processes.
The system detects pairs of gamma rays emitted
indirectly by a positron-emitting radionuclide which is
introduced into the body on a biologically active molecule.
Theemittedparticleapositronrapidlymeetsanelectronand
disappears while two high-energy (511 keV) gamma rays
are emitted (Fig. 2). Those two gamma rays are recorded
with a special camera composed of rings (made with a large
number of tiny crystals) [3]. Using information about
detected rays, a computer calculates the spatial distribution
of the tracer within the patient. Images can be presented as
slices (“Tomography”) or as 3D data.
ThecomputedPETimagesarequantitative,i.e.theyare
measurements–althoughnotperfectlyaccurate–ofthereal
concentration of the tracer in the organ. In clinical practice,
asimpleindexcalledtheStandardizedUptakeValue(SUV)
is generally used. It is defined as the ratio of the
concentration of the tracer in a region to the mean
concentrationinthebody.Thegeneralformulaisasfollows
(althoughtherearevariations,suchastakinginaccountlean
mass or body surface instead of body mass) [4].
tissue concentration (MBq/mL)
SUV =
injected radioactivity (MBq)/body weight(g)
Tumor SUV is usually over 2 in malignant tissue. The
SUV could be useful in the diagnosis and follow up of
cancer diseases, but there is no cut-off value, which
accurately separates malignant and non-malignant uptake
[5]. Moreover, limitations of SUV are known [6]: many
confounding factors influence SUV determination and
criticism of SUV methodology has been made [7].
Limitations include variability in obese patients, and using
lean mass seems to be appropriate to avoid overestimation
[8] in that specific group of patients.The SUVis not always
powerful for discrimination between benign and malignant
tissue (depending on the type of lesion).Then its usefulness
lies more in the longitudinal follow-up than in information
in a unique examination.
PROCEDURE AND RADIONUCLIDES
To conduct the scan, a short-lived radioactive tracer
isotope is injected intra-venously into blood circulation.
The tracer is chemically incorporated into a biologically
active molecule. There is a waiting period while the active
molecule becomes concentrated in tissues of interest; then
thepatientisplacedintheimagingscanner.Duringthescan
arecordoftissueconcentrationismadeasthetracerdecays.
Themostcommonlyusedtraceratpresentistheglucose
analogue FDG (more than 95% of the molecular imaging
procedures make use of FDG at present) for which the
waiting period is typically an hour. FDG is a glucose
molecule in which one hydroxyl group has been exchanged
for an 18F fluorine atom. This molecule is incorporated in
the cells via the same paths as glucose [9]: the expression of
glucosetransportproteins(especiallyGLUT1)allowsFDG
toenterthecell,andFDG,likeglucose,isphosphorylatedby
hexokinase. However its degradation within the cell is
stopped at its second step (FDG-6-phosphate, unlike
glucose-6-phosphate,isnotmetabolizedfurtherbyglucose-
phosphate-isomerase, and can leave the cytosol only by
hydrolysis back to FDG, depending on the phosphatase
activity [10], which is usually rather low). Thus, FDG
accumulation in tissue is proportional to the amount of
glucose utilization. Increased consumption of glucose is a
characteristic of most cancers and is in part related to over-
expression of the GLUT-1 glucose transporters and
increased hexokinase activity.
Fig. 2. Positron emission followed by the disintegration of a
positron-electron couple, which gives two gamma rays
emitted in opposite directions; the information is kept if
two detectors in the ring-shaped detecting device
receive a gamma ray of selected energy; starting from
all detection lines, the computer calculates the position
of the different radioactive sources in the volume.

4. Apollo Medicine, Vol. 7, No. 3, September 2010 192
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One hour after injection, its distribution within the body
depicts the distribution of the glucose uptake. It has been
known for long [11] that the glucose metabolism in most –
but not all – neoplastic tissues is higher than in normal
tissues: primary tumors, recurrences and metastases of
manysolidtumorscanbevisualizedwithFDG-PETasahot
spot amongst low background. The test is performed on
fasting (in order to increase the tracer uptake;
hyperglycemia has been shown to decrease FDG uptake in
tumors[12])andresting(inordertoavoidmuscularuptake)
patients.
Beside the glucose metabolism, many other metabolic
paths, which are disturbed in neoplastic tissues, can be
explored using PET tracers [9]. Table 1 lists some of these
paths relevant in oncology, which can be explored using
PET, and the corresponding most studied tracers.
Combination of PET with CT
The combination of a so-called functional imaging
technique (PET) with an efficient anatomical imaging
technique (CT) is a major breakthrough in modern cancer
imaging. Integrated PET/CT combines PET and CT in a
single imaging device and allows morphological and
functional imaging to be carried out in a single imaging
Table 1. Metabolism or function disturbed in cancer and the PET tracer used for their study [13].
Function/metabolism Tracer
Glucose metabolism 18F-fluoro-deoxy-glucose (FDG)
DNA replication/cellular proliferation 11C-carbon-thymidine
18F-fluoro-thymidine (FLT)
Protein synthesis, amino acid transport 11C-carbon-methionine (MET)
18F-fluoro-ethyl-tyrosine (FET)
18F-fluoro-methyl-tyrosine (FMT)
18F-fluoro-dihydroxyphenylalanine (F-DOPA)
Membrane lipid synthesis 18F-fluoro-acetate
11C-carbon-choline
18F-fluoro-choline (FCH)
Hypoxia 18F-fluoro-misonidazole (FMISO)
64Cu-copper-ATSM
Apoptosis 18F-fluoro-annexin V
Angiogenesis 18F-fluoro-galacto-RDG
Reporter genes 18F-fluoro-deoxyarabinofuranosyl nucleosides
(FEAU, FIAU, FMAU)
Tumor therapy control 18F-fluoro-uracil (FU)
Receptor binding (estrogen) 18F-fluoro-oestradiol (FES)
Receptor binding (somatostatine) 68Ga-gallium- DOTATOC/DOTANOC
procedure, ( Fig.3). Integrated PET/CT has been shown to
be more accurate for lesion localization and
characterization than PET and CT alone or the results
obtained from PET and CT separately and interpreted side
by side or following software based fusion of the PET and
CT datasets. Since 2003, the majority of new clinical PET
devices have been associated with a CT scanner. This
multimodality imaging device performs a PET and a CT
acquisition while the patient remains on the same bed and
provides fused images [14] (where the CT information is
usually coded in gray levels and the tracer uptake in
colors). The two images are perfectly registered [15],
assuming that the patient does not move and that the
organs do not move, which is true in most parts of the body
but could generate artifacts in some areas such as the
diaphragm region [16,17]. Computer-assisted techniques
(so-called gating techniques) are currently being validated
in order to remove or decrease those breathing artifacts
[18,19]. The utility of this dual acquisition procedure is
twofold. First, in order to calculate the spatial distribution
of the tracer, the computer software has to perform some
corrections, which take into account the physical
processes of detection, including the correction of the
gamma rays attenuation by the patient’s body. This can be
corrected if the spatial distribution of the attenuation

5. Review Article
193 Apollo Medicine, Vol. 7, No. 3, September 2010
process is known, which is exactly what the CT images
provide [20]. Compared to the stand alone PET, which
uses a rotating radioactive source to estimate the gamma
rays attenuation, the use of CT data for this purpose has
achieved a major reduction in the acquisition time. The
second and more visible advantage of multimodality
concerns the medical interpretation of the images. A tracer
like FDG has some physiological non-specific (i.e. in
normal tissues) uptake, which varies from one patient to
another. Non-specific uptake could often be misleading or
lead to an undetermined imaging. The fused PET-CT
images are very helpful in localizing the abnormal uptakes
(such as neck or mediastinum lymph nodes) and in
differentiating physiologic from abnormal uptake (for
example in urinary tract, bowels, or in the laryngeal
cavity). Using contrast media for CT even increase the
accuracy of anatomical information. In spite of causing
problems in the correction for attenuation, intravenous
iodinated contrast media injection has several potentials:
better delineation of tumor, mostly for dosimetric planning
of 3D conformal radiotherapy and non-conventional
surgery [21] or when vascular involvement is suspected;
more accurate anatomical localization of tumors in the
head and neck, the abdomen and the pelvis (for instance
localization of an hepatic segment involved by a lesion).
Combination of PET with MRI
Despite the success and popularity of PET-CT and
more recently of SPECT-CT, there are some shortcomings
in the use of CT as the combined anatomical imaging
modality. Firstly, CT adds radiation dose to the overall
examination, particularly if used in a full diagnostic role
with contrast enhancement. Second, CT provides
relatively poor soft tissue contrast in the absence of oral
and intravenous iodinated contrast, particularly if low
dose acquisition protocols are utilized to minimize
radiation exposure. These two theoretical limitations do
not apply to MRI, which does not involve ionizing
radiation and provides soft tissue imaging with high
spatial resolution and superior contrast compared to CT.
MRI can also provide more advanced ‘functional’
techniques such as perfusion and diffusion imaging as
well as spectroscopy, which may be additive to functional
information obtained by PET. Furthermore, the high
sensitivity of PET may also complement the poor signal
strength inherent in current functional MRI imaging. The
combination of PET and MRI into a single scanner may
therefore be the pioneer hybrid imaging modality,
combining the metabolic and molecular information of
PET with the excellent anatomical detail of MRI, while
offering new potential applications with respect to
functional MRI technology.
There are, however, a number of technical problems
that need to be overcome before a clinical hybrid PET-MR
scanner can become a reality. Both MRI and PET have the
potential to affect each other’s performance in their
current form. One of the main problems is that
photomultiplier tubes, a fundamental component of
current PET detectors, will not function in a ‘magnet’ as
the high magnetic field causes electrons to deviate from
their original trajectory, resulting in loss of gain [22]. A
small prototype PET-MRI scanner has been developed
using long optical fibres to transport light from the
detector to photomultiplier tubes situated in a low field
region [22] The potential of using novel readout
technologies insensitive to magnetic fields, including
APDs and Geiger-mode avalanche photodiodes (G-
APDs) has been and still is being explored for further
development.
The first prototype human PET insert, the Brain PET
scanner [23,24], was designed in 2005 using
photodetectors insensitive to magnetic fields (APDs
instead of PMTs) and non-magnetic detector and frontend
electronic materials to operate within a clinical MRI
system. The Brain PET (Fig.4) was designed to operate in
the frequency range of interest for MRI at 3T, allowing
perfect matching with the most sophisticated MR brain
sequences that can be performed at this magnetic field
strength. The first patient images were shown late in 2006
[25] and the system is currently undergoing a detailed
evaluation of mutual interference between the two
imaging modalities and is being used comprehensively to
assess its potential using normal subjects and clinical
studies [26].
Technical limitations
The radioactive half-lives – the period of time over
(a) (b) (c)
Fig.3. (a) CT Scan Organs and bones; (b) PET Scan Cell
activity; (c) PET/CT Scan exact location of high cell
activity.

6. Apollo Medicine, Vol. 7, No. 3, September 2010 194
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which half the radioactive nuclei undergo disintegration –
of the positron emitters are often very short (a few minutes
in the case of radioactive 11C carbon~20 mins, 15O
oxygen~2 mins and 13Nnitrogen~10 mins, and less than 2
h in the case of 18F fluorine [27]). This limitation restricts
clinical PET primarily to the use of tracers labeled with
fluorine-18, which has a half life of ~110 minutes and can
be transported a reasonable distance before use.
The spatial resolution of the human PET cameras is
low, between 6 and 8mm for most of the commercially
available PET scanners [14,28].As a consequence, lesions
under 1 cm could be missed on the images, although
smaller lesions can be seen if they highly concentrate the
tracer. This is probably the most limiting parameter in
medical practice. As compared to CT and MRI, PET
remains a low-resolution technology.
Finally, PET is a very expensive technique. Due to the
short half lives of most radioisotopes, the radiotracers
must be produced using a cyclotron and radiochemistry
laboratory that are in close proximity to the PET imaging
facility. Few hospitals and universities are capable of
maintaining such systems, and most clinical PET is
supported by third-party suppliers of radiotracers which
can supply many sites simultaneously. The half life of
fluorine-18 is long enough such that fluorine-18 labeled
radiotracers can be manufactured commercially at an
offsite location.
OTHER LIMITATIONS
Normal uptake reduces the usefulness of FDG: this
tracer is not efficient for the diagnosis of brain metastases
since there is a high physiological uptake of FDG by the
normal brain.
Another limitation of FDG is the non-specific uptake
by inflammatory and granulomatous lesions. This can lead
to overestimate the spread of a malignant disease or to
doubtful interpretation.
Finally FDG uptake is influenced by both insulin and
blood glucose levels. The performance of the FDG-PET
could then be altered in non compliant patients or in
diabetic patients (if the timing between anti-diabetic
treatment and the injection of FDG is not carefully
planned).
Because the radioactive substance decays quickly and
is effective for only a short period of time, it is important
for the patient to be on time for the appointment and to
receive the radioactive material at the scheduled time.
Thus, late arrival for an appointment may require
rescheduling the procedure for another day.
A person who is very obese may not fit into the
opening of a conventional PET/CT unit.
SAFETY
PET scanning is non-invasive, but it does involve
exposure to ionizing radiation. The total dose of radiation
is not insignificant, usually around 5-7 mSv. However, in
modern practice, a combined PET/CT scan is almost
always performed, and for PET/CT scanning, the
radiation exposure may be substantial - around 23-26 mSv
(for a 70 kg person - dose is likely to be higher for higher
body weights) [29].
The radiation dose of FDG is approximately 2 × 10–2
mSv/MBq according to ICRP publication 106 [30], i.e.
about 3-4 mSv for an administered activity of 185 MBq.
The radiation exposure related to a CT performing a PET/
CT examination depends on the intention of the CT
carried out and may differ from case to case: the CT can be
performed as a low-dose CT (with lower voltage and
current) to be used for attenuation correction and
localisation of PET lesions [31]. Alternatively (or
additionally) a diagnostic CT can be indicated (in most
cases with intravenous contrast agent application and deep
inspiration in case of a chest CT) for a full diagnostic CT
examination. The effective CTdose could range from 1-20
mSv and may be even higher for a high resolution
diagnostic CT scan. Given the variety of CT systems and
protocols the radiation exposure for a PET/CT
examination should be estimated specific to the system
and protocol being used and an expert from radiology or
guidelines provided by the European radiological
Fig.4. Brain PET/MRI fusion image

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195 Apollo Medicine, Vol. 7, No. 3, September 2010
societies should be consulted regarding effective dose
from the CT examination.
Indications
Some of the current applications of PET and PET/CT
are in:
• Oncology–identifying and determining the extent of
malignant disease and monitoring therapy of
numerous cancers
• Cardiology – detecting coronary artery disease and
assessing whether dysfunctional myocardial tissue is
viable
• Neurology and psychiatry – differentiating between
tumor recurrence and radiation necrosis,
differentiating Alzheimer disease from other
dementias, and locating epileptic foci.
Oncology
Primary presentation: diagnosis: unknown primary
malignancy,differentiationofbenignandmalignantlesions
of e.g. a solitary lung nodule, Fig.5, especially in case of
discrepant clinical and radiological estimates of the
likelihood of cancer;
Staging on presentation: non-small-cell lung cancer,T3
esophageal cancer, Hodgkin’s disease, non-Hodgkin’s
lymphoma, locally advanced cervical cancer, ENT tumors
with risk factors and locally advanced breast cancer.
Response evaluation: malignant lymphoma, GIST, at
present other applications only in a research setting.
Application for esophageal, colorectal, lung and breast
cancer appear promising.
Restagingintheeventofpotentiallycurablerelapse(for
FDG avid tumors).
Establishing and localizing disease sites as a cause for
elevated serum markers (e.g. colorectal, thyroid, ovarian,
cervix, melanoma, breast and germ–cell tumors).
Image guided biopsy (e.g. brain tumors) and
radiotherapy planning.
RADIATION THERAPY PLANNING
To be cured by radiation therapy, a tumour must be
entirely contained within a volume of tissue treated to a
tumouricidaldose.Patientsselectedforcurativeor‘radical’
radiationtherapymusthavediseaseconfinedtoaregionthat
can be safely treated to the chosen tumouricidal dose. An
optimum radiation therapy plan will deliver a sufficiently
high dose of radiation to attain durable local tumour control
while delivering the least possible dose to the smallest
possible volume of critical normal tissues. To plan
potentially curative radiation therapy, the precise location
and extent of the tumour must be known.
Rapidandcontinuingadvancesincomputerassisted3D
planning have resulted in developments such as three
dimensional conformal radiotherapy (3DCRT) and
intensity modulated radiation therapy (IMRT) [33]. These
methodscanfacilitatethedeliveryofhigherradiationdoses
to the tumour [34,35] and allow relative sparing of normal
tissues,withpotentialforhighertumourcontrolratesand/or
less toxicity for the patient (Fig.6).
To take full advantage of these dramatic advances in
modern radiotherapy, the most accurate and precise
delineation of the target is needed. In the pre-PET era,
definition of tumour volumes and treatment volumes was
based primarily on structural imaging with contrast CT or
MRI, which together with clinical judgement were used to
estimatethelikelyextensionofmicroscopicdiseaseineach
case and thereby define the CTV. Molecular imaging, using
radioisotopetracerstoidentifymoleculartumourtargets,in
combination with PET and single photon emission
tomography (SPECT), has allowed a more complex
functional and biologic evaluation of tumours. In many
tumour types, clinicopathological studies have shown that
the estimate of tumour extent is most accurate when
functional and structural imaging data are combined. With
rapid advances in molecular imaging and the increasing
Fig.5 Patient 1: (Left) 1.6-cm right lower lobe pulmonary
nodule on CT (yellow arrow). (Right) Superimposed
FDG PET image shows hypermetabolism (biopsy-
proven adenocarcinoma). Patient 2: (Left) 1.3-cm right
lower lobe pulmonary nodule (red arrow). (Right) PET/
CT does not show increased FDG uptake, which is
stable on follow-up CT examinations [32].

8. Apollo Medicine, Vol. 7, No. 3, September 2010 196
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availability of integrated positron emission tomography/
X-ray computed tomography (PET/CT) and single photon
emission computed tomography/C ray computed
tomography (SPECT/CT) systems, it is now possible to
introduce a new dimension to radiation treatment planning
beyond the structural information offered by conventional
imaging techniques [37]. SPECT due to its relatively poor
resolution, makes it inferior to PET.
Dedicated PET scanner vs gamma-camera PET
PET imaging is best performed using a dedicated PET
scanner. However, it is possible to acquire PET images
usingaconventionaldual-headgammacamerafittedwitha
coincidence detector.The quality of gamma-camera PETis
considerablylower,andacquisitionisslower.However,for
institutions with low demand for PET, this may allow on-
site imaging, instead of referring patients to another center,
or relying on a visit by a mobile scanner.
SPECT-CT imaging
In single-photon emission computed tomography
(SPECT),afteraradionuclideisinjected,singlegamma-ray
photons that exit the body are captured by a standard
gamma-ray camera. The camera sequentially acquires
images from multiple projections as it moves over 360- or
180-degree arcs about the body. This raw information is
then reconstructed into tomographic image sets. SPECT/
CT systems have the same SPECT component as
conventional nuclear medicine systems, the dual-head
gamma cameras are generally used for planar and
tomographic imaging of single photon emitting
radiotracers. The CT component of the first-generation
hybrid devices used a low resolution CT detector while
recentlydeveloped,second-generationSPECT/CTsystems
incorporate a variety of multi-slice CT scanners. SPECT/
CTsystemsincludeseparateCTandgammacameradevices
usingcommonoradjacentmechanicalgantries,andsharing
the same scanning table. Integration of SPECT and X ray
imagingdataisperformedbyaprocessthatissimilartothat
of PET/CT. SPECT and CT images are displayed on the
same screen in addition to the fused images, which
representtheoverlayofacolouredSPECToveragrey-scale
CT image. A3-D display with triangulation options allows
to locate lesions and sites of interest on the CT image and to
redisplay them on the registered SPECT and fused SPECT/
CT images.
Applications of SPECT-CT
The superiority of SPECT/CT over planar scintigraphy
or SPECT has been clearly demonstrated for the imaging of
thyroid cancer (Fig.7), neural crest and adrenal tumors
(Fig. 8), neuroendocrine cancer, benign and malignant
skeletaldiseases(Fig.9),parathyroidadenoma(Fig.10)and
mapping of sentinel lymph nodes (Fig.11) in the head and
neck and in the pelvic region.
PET vs conventional SPECT imaging
PET has several advantages over conventional SPECT
imaging. Its spatial resolution is about two times better, and
it accurately corrects for attenuation (absorption by
interposed tissue) of photons emitted from the organ of
interest. The attenuation correction process is faster using
the PET/CT technique. Because PET images are corrected
forattenuation,theymoreaccuratelyreflectthetrueactivity
of the tracer in tissue.
(a) (b)
(c) (d)
Fig.6 NSCLC arising in the left upper lobe. The associated
atelectasis did not show 18FFDG- uptake, and was
therefore excluded from the GTV. Axial (a) and sagittal
(b) CT reconstruction fused with 18F-FDG-PET
reconstruction. The GTV (red; (c) was designed using
a source/background algorithm. Recruited for the
German PET-Plan study (pilot-phase), the patient
received radio-chemotherapy with radiation confined
to the 18F-FDGpositive area (treatment plan; (d))
escalated up to 74 Gy (1,8 Gy daily) [36].
Fig.7. I-131 whole body scan. (A) Planar images showing
focal uptake in left thorax (B) SPECT/CT confirms the
uptake in right 9th
rib posteriorly.
(a) (b)

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197 Apollo Medicine, Vol. 7, No. 3, September 2010
Fig.9. Patient with lung cancer and 2 hot spots, in lower lumbar
spine and pelvis (os sacrum). (A and B) Planar
scintigrams from skeletal scintigraphy (99mTc-
hydroxymethylene diphosphonate). (C) Detailed view
of pelvis with 2 hot spots (arrows). (D) Transverse
section of upper lesion in lumbar vertebra 5. (E) Small
osteolytic lesion with intense tracer uptake indicating
bone metastasis in lower pelvis. (F) Fused image. (G
and H) Spondylarthrosis of right facet joint with intense
tracer uptake indicating degenerative lesion [38].
Fig.8. Diagnosis of pheochromocytoma with 99mTc-MIBG
SPECT/CT. (A) Planar image showing mildly intense
focal lesion extending to left suprarenal area. (B–D)
Corresponding sections of SPECT (B), CT (C), and
fused SPECT/CT (D) images showing focal uptake
extending to enlarged left adrenal gland, indicating
pheochromocytoma. (E–G) Corresponding transverse
sections of right adrenal gland showing additional hot
spot and enlargement of gland, indicating second
pheochromocytoma, which was proven histologically.
Lesion may be missed on planar image (A) or
overexposed transaxial SPECT image (B) [38].
Fig.10. Parathyroid scintigraphy with SPECT/CT. (A and B)
Planar views of 99mTc-MIBI scintigraphy 60 min (A)
and 15 min (B) after 99mTc-MIBI injection. Arrows
indicate lesions. (C) Transverse section of 99mTc-MIBI
SPECT showing mildly intense focal lesion in right
lower neck region (arrow). (D and E) Corresponding
CT section (D) and fused image (E) indicating
parathyroid adenoma below right thyroid gland
(arrows). (F and G) Demonstration of parathyroid
adenoma (arrows) in corresponding coronal CT (F) and
SPECT/CT (G) images [38].
of image fusion involving a large number of patients has
been achievedwith PET/CT. The design properties of PET/
MRIareunderconsideration,andprogresshasalreadybeen
made in this field with small animal scanners. The next
generation of PET/CT technology is likely to make use of
new radiation detectors and electronics. Discussions are
now focusing, for example, on the reductionof whole-body
imaging times to less than 15 min and the introduction of
routine respiratory and cardiac gating for improvement of
lesion localization and margin definition. Multiple slice
spiral CT scans will open the way for cardiac imaging, and
interesting developments are expected in this field, which,
Future developments
Multimodality imaging is here to stay and image fusion
willbecome routine. The first truly routine implementation
Fig.11 Sentinel node localization with 99mTc-Scintiscint [38].

10. Apollo Medicine, Vol. 7, No. 3, September 2010 198
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aswithnuclearmedicineingeneral,isheavilydependenton
the emergence of new, clinically useful ligands. There is
realistic hope that these new ligands will lead to novel
practical applications in neurology, cardiology and
oncology. As individually tailored medicines begin to
impact on healthcare, these technologies will find special
relevanceindeterminingpatientresponsetothesetherapies.
An early indicator of lack of response may be not only
beneficialbutalsoimmenselyimportantineconomicterms.
The future for PET/CT imaging as a surrogate endpointfor
novel therapeutic interventions is bright. This will imply a
rethink of traditional criteria for lesion response –
conventionalRECISTcriteriawillneedtobere-assessedin
the light of the metabolic parameter made available by PET
[39,40].
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