PET and SPECT Imaging in Veterinary Medicine

Amy K. LeBlanc, DVM, DACVIM,* and Kathelijne Peremans, DVM, DipECVDI, PhD†

Veterinarians have gained increasing access to positron emission tomography (PET and PET/
CT) imaging facilities, allowing them to use this powerful molecular imaging technique for
clinical and research applications. SPECT is currently being used more in Europe than in the
United States and has been shown to be useful in veterinary oncology and in the evaluation of
orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate
behavioral disorders in animals that have interesting similarities to human psychiatric
disorders. This article provides an overview of the potential applications of PET and SPECT.
The use of commercially available and investigational PET radiopharmaceuticals in the
management of veterinary disease has been discussed. To date, most of the work in this
field has utilized the commercially available PET tracer, 18F-fluorodeoxyglucose for oncologic
imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and
birds) have been published to assist in lesion detection and interpretation for veterinary
radiologists and clinicians. Studies evaluating other 18F-labeled tracers for research applica-
tions are underway at several institutions and companion animal models of human diseases
are being increasingly recognized for their value in biomarker and therapy development.
Although PET and SPECT technologies are in their infancy for clinical veterinary medicine,
increasing access to and interest in these applications and other molecular imaging
techniques has led to a greater knowledge and collective body of expertise for veterinarians
worldwide. Initiation and fostering of physician-veterinarian collaborations are key compo-
nents to the forward movement of this field.
Semin Nucl Med 44:47-56 C 2014 Elsevier Inc. All rights reserved.

Historical Perspective: PET computed tomography (PET/CT) assists in image interpreta-

Imaging in Veterinary Medicine
P ET imaging is considered relatively new to veterinary
medicine, with the first reports of its use in clinical patients
dating to the early 1980s and 1990s.1-4 This is attributable to
the limited access to PET scanners owing to their purchase and
maintenance costs, reliance on discretionary income for pet
owners to fund veterinary care for their pets, and the still-
evolving knowledge of what role this technology plays in the
management of common veterinary ailments. There is an
ongoing need to validate the technique and increase the
comfort level for veterinary radiologists and clinicians involved
in reading such studies. The widespread fusion of PET with
*Department of Small Animal Clinical Sciences, University of Tennessee
College of Veterinary Medicine, Veterinary Teaching Hospital, Knoxville,
TN.
†Department of Medical Imaging and Small Animal Orthopaedics, Faculty of
Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Address reprint requests to Amy K. LeBlanc, DVM DACVIM, Department of
Small Animal Clinical Sciences, University of Tennessee College of
Veterinary Medicine, 2407 River Dr, Rm C247 Veterinary Teaching
Hospital, Knoxville, TN 37996. E-mail: aleblanc@utk.edu
tion, as CT is a common component of veterinary diagnostic
imaging, and a review of both data sets can assist the clinician
in characterizing areas of radiopharmaceutical uptake.5
The most logical and widely published studies for PET and
PET/CT imaging, utilizing the commercially available tracer
18
F-fluorodeoxyglucose (18F-FDG), are in the field of oncol-
ogy, where the most human PET studies are performed.
Veterinary oncology is a growing field and a recognized
specialty of the American College of Veterinary Internal
Medicine, founded in 1972 (www.acvim.org). Currently, most
veterinarians rely on standard anatomical imaging modalities
such as radiography, ultrasonography, and computed tomog-
raphy for detection and staging of cancer in veterinary patients.
The use of PET offers an opportunity to evaluate the metabolic
nature of malignancies in addition to anatomical data. Natu-
rally occurring cancers in dogs and cats represent a great
opportunity to validate PET and PET/CT imaging techniques,
they benefit tumor-bearing pets while simultaneously advanc-
ing development of new imaging techniques for human
cancers. This aspect of veterinary medicine is gaining traction
in academic settings where research collaborations between
veterinarians and physicians are established and growing.

0001-2998/14/$-see front matter & 2014 Elsevier Inc. All rights reserved. 47
http://dx.doi.org/10.1053/j.semnuclmed.2013.08.004
48 A.K. LeBlanc and K. Peremans

PET Imaging Protocols and Data

Analysis for Companion Animals
Several key differences exist in patient preparation for animals
undergoing PET and PET/CT imaging. Veterinary PET scans
involve preparation for general anesthesia, including 8-12
hours fast, which is required for proper positioning for the
scan procedure, but also serves to limit physiological 18F-FDG
myocardial uptake. Additionally, state-specific radiation safety
guidelines may apply and must be followed to limit exposure to
the animals and their excreta once they have been injected with
the radiopharmaceutical of interest.6 Readers may refer to
http://www.nrc.gov/material/miau/med-vet/html for additional
details.
In the case of 18F-FDG, artifactual uptake within skeletal
muscle can occur if the animal is physically active in the uptake
period before the scan, hence the use of a sedative or
premedicant is recommended (Fig. 1). In addition, in the case
of 18F-FDG and similarly to humans, animals should be
normoglycemic so as not to interfere with tissue uptake of the
radiopharmaceutical, which can lead to erroneous scan results.
Other key components are adequate facilities for holding
radioactive animals and protocols for transport to off-site
facilities (if applicable), monitoring radiation exposure to staff,
and release limits for pets to return home to their owners.
Along with a greater body of experience in reading PET and
PET/CT studies, there remains a need for standardized post- Figure 1 Maximal image projections (MIPs) of an 8-year-old mixed-
image processing and data analysis in veterinary PET imaging. breed dog with high-grade multicentric lymphoma, before (left) and
The commonly used clinical indicator of radiopharmaceutical after (right) receiving a CHOP-based induction chemotherapy pro-
uptake is the standardized uptake value, which is influenced tocol. Imaging was carried out with approximately 5 mCi 18F-FDG
(PETNET Solutions, Knoxville, TN) allowing a 60-minute uptake
by many factors (scanner design and reconstruction parame-
time and using a Siemens mCT scanner (Siemens Molecular Imaging,
ters, patient body condition, scan protocol, etc.).7 Guidelines Knoxville, TN). On the baseline scan, 18F-FDG uptake is present in
for objective evaluation of PET/CT–based responses (positron affected lymph nodes (arrows, left image) with splenomegaly con-
emission tomography response criteria in solid tumors) were sistent with malignant infiltration (arrow head, left image). Physiolo-
recently reported for human patients in whom PET/CT is used gical 18F-FDG uptake is present within the brain, heart, and salivary
to judge response to therapy.8 The use of such a uniform glands, which is difficult to discern with bulky head and neck
reporting method for factors affecting the generation of a PET lymphoma involvement. Normal excretion of tracer is evident in renal
image is needed so that data can be reproduced at other PET pelves and bladder. Notably within the remission scan, artifactual yet
imaging centers and in support of multisite clinical trials that physiological uptake is noted within the musculature of the forelimbs,
involve PET imaging. consistent with physical activity during the tracer uptake period
(arrows, right image). Myocardial uptake is notably increased on the
remission PET scan (arrow head, right image), indicating the
variability of 18F-FDG myocardial uptake even in the fasting state.
PET Radiopharmaceutical CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone

Biodistribution Studies in Of particular interest for oncology, biodistribution data in

dogs and cats with 18F-fluorothymidine (18F-FLT) is currently
Companion Animals in progress. We believe this cellular proliferation tracer will
In an effort to characterize the normal patterns of uptake for provide valuable information for lesion discrimination when
18
F-FDG, studies in purpose-bred dogs and cats utilizing both staging animals with cancer.
PET and PET/CT have been published.9-11 An investigation of
how various anesthetic protocols influence brain uptake of
18
F-FDG was also performed for future studies of 18F-FDG in
Application of Selected PET
neuroimaging.12 These studies act not only as valuable data Radiopharmaceuticals to
sets for comparative studies between species and provide a Veterinary Nuclear Medicine
reference for disease studies, but they also act as feasibility 18
studies when human PET imaging facilities are used for animal F-FDG
18
work. Additionally, studies in birds have been performed and F-FDG is the standard PET radiopharmaceutical for cancer
highlight the comparative differences for avian species.13,14 imaging in humans, but it is also utilized for cardiac imaging
PET and SPECT imaging in veterinary medicine 49

and neuroimaging purposes. Veterinary applications of

18
F-FDG-PET/CT in oncology are growing with increasing
access to scanners, pet owners' growing requests for equivalent
care to humans, and experience with PET imaging protocols.
Several studies demonstrate the avidity of canine cancers for
18
F-FDG and emphasize the potential of whole-body PET and
PET/CT as an efficient staging technique that can identify
lesions not detected on physical examination that may
represent additional sites of metastasis or additional unrelated
malignancies or both.15-18 Serial 18F-FDG-PET/CT imaging is
attractive for monitoring response to therapy in a single
diagnostic procedure (Fig. 2). Investigations of this approach
in canine cancers treated with a tyrosine kinase inhibitor
showed discordance between standard response evaluation
criteria in solid tumors and positron emission tomography
response criteria in solid tumors applied to selected neoplastic
lesions, emphasizing the need for larger clinical studies of serial
18
F-FDG-PET/CT in this area.19
Imaging of inflammatory processes with 18F-FDG is well
established in humans and the application of this technique to
veterinary medicine is ongoing, particularly in the field of
neuroimaging for inflammatory central nervous system dis-
eases.20 Fungal granulomas and other systemic infectious
diseases could be tracked with serial PET/CT to determine
the response to antimicrobial or antifungal therapy.3,4

18
F-FLT
18
F-FLT, is a substrate of the mammalian thymidine kinase, an
integral part of the cellular DNA synthesis machinery and thus
a reflection of cellular rate of proliferation. Many studies
demonstrate a strong correlation between 18F-FLT uptake
and cell proliferation, as assessed by the Ki-67 immunostaining
technique.21 However, the consideration of the cell population
of interest and other factors that may affect uptake of 18F-FLT,
such as cellular thymidine and thymidine kinase 1 levels, are
important when interpreting the validity of an 18F-FLT
signal.22 Although 18F-FLT uptake in reactive lymphoid
hyperplasia, mediated by B-lymphocyte proliferation in ger-
minal centers does occur, some studies demonstrate the
superiority of 18F-FLT over 18F-FDG for differentiation of a
tumor from an inflammation23 and indicate that 18F-FLT
could be a useful adjunct to 18F-FDG to improve diagnostic
specificity.24 Clinical investigations using 18F-FLT are primar-
ily in oncology, where response to therapy may be judged
based on changes in tumor cell proliferation. Additionally, this
technique may provide increased specificity over 18F-FDG in
the evaluation of cancers that are metastatic to lymph nodes
or may incite an inflammatory response, or both (Fig. 3).
A study evaluating whole-body 18F-FLT-PET/CT as a non-
invasive measure of response to a novel nucleoside analogue
for canine lymphoma therapy demonstrated the utility of this
proliferation tracer as an early marker of response or as an
indicator of relapsed disease or both.25
Researchers at the University of Tennessee studied the
whole-body biodistribution of 18F-FLT in normal cats and
dogs and applied serial 18F-FLT imaging in a canine model of
chemotherapy-induced myelosuppression.26 Physiological
Figure 2 Maximal image projections (MIPs) of a 6-year-old standard
Poodle with stage V malignant oral mucosal melanoma, before (left)
and after (right) receiving an investigational immunotherapy treat-
ment protocol. Imaging was carried out with approximately 5 mCi
18
F-FDG (PETNET Solutions, Knoxville, TN), allowing a 60-minute
uptake time, and using a Siemens mCT scanner (Siemens Molecular
Imaging, Knoxville, TN). Uptake within the primary tumor of the
maxillary mucosa is evident, along with bulky mandibular lymph
node metastasis (arrow heads) and multiple pulmonary metastases
(arrows). Physiological uptake is noted on both scans within the brain
and gastrointestinal tract; minimal myocardial uptake is also present.
Residual tracer is also present within the injection site on the distal
forelimb. Excretion of 18F-FDG is evident within the renal pelves and
urinary bladder. Comparison of the baseline and posttreatment scans
is supportive of progressive disease, with no measurable response to
therapy.
uptake of 18F-FLT within the bone marrow allows for the
PET imaging of leukemias and other primary bone marrow
disorders (myelodysplastic syndrome, aplastic anemia, and
idiopathic marrow fibrosis) in which the patient's bone
marrow 18F-FLT signal can be monitored noninvasively over
time, thereby providing an early biomarker of treatment
response.27,28 18F-FLT-PET/CT may also be applied to
identify the bone marrow in external-beam radiotherapy
planning so as to limit the dose in chemoradiation schemes,
which carry a significant risk for myelosuppression.29 The use
of 18F-FLT for the imaging of spontaneous tumors in dogs
could be used to gather the necessary data for eventual Food
and Drug Administration approval of 18F-FLT for human use
in these and other clinical scenarios.
50 A.K. LeBlanc and K. Peremans

Figure 3 MIPs of an 11-year-old neutered male dog with a large hepatocellular carcinoma with central necrosis, imaging
done with both 18F-FLT and 18F-FDG (5 mCi for each radiopharmaceutical, allowing a 60-minute uptake time, and using
a Siemens mCT scanner (Siemens Molecular Imaging, Knoxville, TN). Within the 18F-FLT-PET images, intense tracer
uptake is evident within the bone marrow and the viable edges of the hepatic tumor, shown to be mitotically active on
histopathology. As expected, no brain or myocardial uptake of 18F-FLT is seen. The borders of the hepatic tumor in this dog
appear more sharply defined with 18F-FLT (SUVmax ¼ 13.1) compared with 18F-FDG imaging (SUVmax ¼ 4.5). In the
18
F-FDG-PET images, physiological tracer uptake is present within the left mandibular salivary gland, brain, myocardium,
GI tract, and urinary tract. Although not confirmed with histopathology, a presumed reactive retrosternal lymph node
(arrows) demonstrates avidity for 18F-FDG (SUVmax ¼ 10.7) but not 18F-FLT (SUVmax ¼ 1.8). GI, gastrointestinal; MIPs,
maximal image projections; SUV, standardized uptake value.

18 imaging, which has implications for radiotherapy dosimetry

F-Sodium Fluoride (18F-NaF)
18
F-NaF was first used for skeletal scintigraphy in the 1960s,
but was replaced by 99mTc diphosphonate because of the cost
and wide availability of clinical planar and SPECT gamma
cameras in both human and veterinary medicine. Recently,
18
F-NaF has been reevaluated and is gaining popularity for
bone imaging mainly because of the technological advances
made possible with PET/CT. This technique provides greater
sensitivity, resolution, and efficiency for whole-body skeletal
studies. 18F-NaF has a high and rapid uptake in the bone with
rapid blood pool clearance, producing high target-background
ratios less than 1 hour after injection in both humans and
dogs.30,31 Based on the human experience, 18F-NaF should be
useful for characterization of primary and metastatic bone
lesions. Additional work to support this technique over
traditional bone scans for skeletal diseases in veterinary nuclear
medicine is needed.
Investigational PET
Radiopharmaceuticals and Their
Applications
18
F-Misonidazole and 64CU-ATSM for Hypoxia
Imaging
Spontaneous canine malignancies offer a unique opportunity
for radiopharmaceutical development. In the field of hypoxia
and development of therapies to specifically address cellular
changes associated with hypoxia, both 18F-misonidazole and
64
CU-ATSM have been studied in an effort to garner data to
support the commercialization of such tracers and their
application to clinical situations. Radiation dose planning
and prescription based on hypoxia imaging could complement
traditional techniques by providing insight into areas of the
tumor that may benefit from a boost of therapeutic radiation or
novel intensity-modulated radiotherapy protocols or both.
Canine tumor imaging with both 18F-misonidazole and 64CU-
ATSM demonstrates the applicability of these naturally occur-
ring cancer models for the development and refinement of
such tracers.32-35
18
F-fluorothiaheptadecanoic acid (18F-FTHA)
The palmitate analogue 14(R,S)-(18F-FTHA) accumu-
lates preferentially within the myocardium via beta-
oxidative metabolic trapping.36-38 Intense myocardial
uptake, long myocardial retention, and rapid clearance
from the bloodstream make 18F-FTHA a useful PET
imaging agent, and it shows a vast improvement over
previous efforts to interrogate the fatty acid oxidation
pathway with C-11 labeled fatty acids, which were
difficult to model and required on-site cyclotron
facilities owing to the 20-minute half-life of C-11. Our
group has studied the whole-body biodistribution of
PET and SPECT imaging in veterinary medicine 51

18
F-FTHA in the normal cat and has compared the percentage due to thyroid carcinoma.39 In dogs, thyroid
uptake kinetics of both 18F-FTHA and 18F-FDG in this tumors are more likely to be malignant.40 Pertechnetate is
species. Based on the biodistribution of 18F-FTHA in the the classic radionuclide used for diagnosis of thyroid disease
domestic cat, application of this PET tracer for cardiac, in cats and dogs and planar imaging is usually sufficient for
hepatic, and renal function seems plausible. Additional imaging of the primary lesion. Canine thyroid tumors tend to
work is needed to define the role of 18F-FTHA for cardiac metastasize to regional lymph nodes and lungs at an early
PET imaging in both humans and companion animals. stage. Similar to human medicine, the sensitivity of planar
imaging is much less than SPECT for metastasis detection
except in an advanced stage. SPECT is not only used for
SPECT diagnostic and staging purposes in dogs but also posttherapy
to evaluate radioiodine uptake in the primary tumor and its
Planar gamma camera imaging has been used in veterinary metastasis (Fig. 4).
medicine for decades, at first predominantly in the diagnostic
workup of equine lameness cases but later for small animal
application. However, tomographic studies (SPECT) have not
received much enthusiasm in veterinary medicine despite the
Insulinomas
fact that many preclinical human medicine studies exist, Insulinomas are rare tumors in dogs and cats.41,42 Clinical
mainly in dogs, but also in cats. This may be partially explained features can be vague and the presence of hypoglycemia in the
by the lack of suitable equipment (many veterinary gamma face of increased insulin levels can be a diagnostic indication,
cameras are used for both large and small animal imaging but but hypoglycemia as such is an aspecific sign and insulin levels
have been rebuilt to meet the specific requirements for equine may be normal. In 50% of the dogs insulinomas metastasize to
imaging), specific software, and the necessity for anesthesia. In the liver and lymph nodes.42 Ultrasonography is commonly
equipment also used to image horses, the size of the animal used as the next diagnostic step but may be unrewarding to
is an additional restriction as only limited areas are accessible to localize and characterize the primary tumor or its metastases.
SPECT. Contrary to studies in man, anesthesia or sedation is an Somatostatin receptor scintigraphy, with radiolabeled octreo-
absolute prerequisite for SPECT investigations, which has tide or depreotide, has been successfully used in dogs
further limited its use. Ischemic heart disease is not a clinical suspected of an insulinoma (Fig. 5). Using SPECT and
problem in our canine and feline patients, so there is not as in-vitro autoradiography, Robben et al.43 demonstrated that
high a demand for cardiac SPECT as in human medicine. Most uptake of the radiopharmaceutical was linked with over-
functional imaging of the heart in veterinary medicine is carried expression of one type of somatostatin receptor as opposed
out by echocardiography. There is not much interest in
veterinary medicine for brain perfusion and neuroreceptor
imaging where SPECT is essential. However, in the last
decades, developments in small animal medicine, especially
in oncology and behavioral medicine, prompted the introduc-
tion of more advanced diagnostic tools. Many owners regard
their pets as part of the family and as such want the optimal
(anthropomorphic) care for them. Because of the internet,
owners have become increasingly aware of the variety in
diagnostic and therapeutic possibilities. In addition, sophisti-
cated processing software has become more accessible, thereby
making coregistration with CT or MRI, or both, now part of the
veterinary armamentarium. In this regard, diagnostic and
therapeutic approaches in sick animals reflect, to a certain
extent, those of human medicine but with financial restric-
tions, especially regarding some radiopharmaceuticals. In this
section, the practical application of SPECT in different clinical
settings has been expounded. New techniques, as applied in
veterinary medicine, have also been briefly mentioned where
applicable.

Oncology
Thyroid Carcinoma
In aging cats, hyperthyroidism is one of the most common
endocrine disorders, with the majority due to benign
adenomas or adenomatous hyperplasia and only a small
Figure 4 Coronal plane SPECT (summed slices) image acquired after
radioiodine-131 treatment. There is an intense area of uptake in the
cervical region from a thryoid carcinomal with 2 focal areas of less
intense uptake (arrows) due to metastases in the thorax.
52
Figure 5 Coronal plane SPECT images (summed slices) of the anterior
abdomen following injection of 123I-MIBG. There are 2 focal areas of
increased uptake within the liver and a patchy area of increased uptake
(arrow) also within the liver. Postmortem examination confirmed
nodular metastatic lesions (2 focal lesions) together with massive
tumor infiltration in the liver.
to human insulinomas, where subtypes occur with lower
affinity for octreotide. In a comparative study, the same authors
compared CT, ultrasonography, and somatostatin receptor
scintigraphy SPECT to evaluate their potential to demonstrate
the primary tumor and metastatic disease.44 A higher number
of primary tumors and metastases to the lymph nodes were
found on CT images. However, because of the high number
of false positives, CT was unreliable to provide a definitive
diagnosis of metastatic involvement. The false-negative results
of SPECT seemed to be predominantly related to low (spatial)
resolution. Small lesions (median 15 mm) were missed and
uptake was not always allocated to the correct anatomical area.
The introduction of resolution recovering software and fusion
with anatomical imaging may increase the preoperative value
of CT and SPECT in the staging and characterization of canine
insulinomas.
Pheochromocytoma
These catecholamine-producing neuroendocrine tumors
are uncommon in dogs and cats and the diagnosis can be a
challenge. Clinical symptoms can be vague and hyper-
tension may be phasic, thus failure to demonstrate hyper-
tension does not exclude a pheochromocytoma. Diagnosis
is often based on the detection of excessive catecholamines
(epinephrine and norepinephrine) or their metabolites
(metanephrine and normetanephrine). Urine concentra-
tions of these products have been recently evaluated with
the best promise associated with normetanephrine-
creatinine ratios but these tests are not widely available.45
This tumor tends to be locally invasive and can metastasize
to a range of organs. Ultrasonography is the first-line
medical imaging tool and is useful to identify an adrenal
associated mass; however it is not possible to differentiate
pheochromocytoma from other types of adrenal masses.
123
I-metaiodobenzylguanidine (123I-MIBG) has been used
in dogs for pheochromocytoma detection, however only
planar imaging has been reported.46 We performed
123
I-MIBG SPECT studies in dogs suspected of a pheo-
chromocytoma. In most of these dogs, the adrenal medulla
was clearly recognized at 6 hours and remained visible 24
A.K. LeBlanc and K. Peremans
hours following injection. In humans, normal uptake in
the medulla has been reported ranging from 30%-80% for
123
I-labeled MIBG.47,48 In 1 dog, focal uptake was seen in
a caudal lung lobe at 6 hours but not at 24 hours. This area
of uptake coincided with a patchy area of increased
attenuation on CT scan. Lung biopsy revealed focal
atelectasis. In humans, both decreased and increased
pulmonary tracer washout has been reported to reflect
changes in vascularization status of the lungs and endo-
thelial integrity.49
Brain imaging
Perfusion Imaging
99m
Both Tc-hexamethylpropyleneamine oxime and
99m
Tc-ethyl cysteinate dimer (ECD) with conventional colli-
mated gamma cameras can be used for brain imaging in dogs.
Injection of the tracers is performed in quiet surroundings with
dimmed lights (similar to what is the standard protocol in
human medicine) and before sedation and anesthesia. 99mTc-
ECD studies have shown an influence of sedatives and
anesthetics on regional cerebral blood flow (rCBF) when given
before the tracer, with regional increases and decreases depend-
ing on the drug used.50,51 Dogs have a faster uptake and
washout rate of 99mTc-ECD than men, therefore the optimal
scan interval after tracer injection is 15-40 minutes.52,53
Comparison of the rCBF measured with 99mTc-ECD and
99m
Tc-hexamethylpropyleneamine oxime revealed that, similar
to man, regional distribution differences exist between both
tracers, indicating that direct comparison of data obtained with
these tracers is not possible.54,55 Most perfusion studies have
been conducted in animals with behavioral disorders including
impulsive aggression, pathologic anxiety, and compulsive
behavior. In 2 recent studies, decreased left frontal and right
temporal perfusion was found in impulsive-aggressive dogs
and decreased left frontal, increased right temporal, and
decreased subcortical blood flow was registered in dogs with
anxiety disorders.56,57 The hypoperfusion in the frontal cortex,
reflecting hypofunctionality, is consistent with the major
involvement of this area in behavior in general and its control
over limbic primary reactions, generated by structures located
in the temporal and subcortical regions, in particular.58 Beside
the fact that these data provide information on the pathophy-
siological mechanisms underlying canine behavioral disorders,
the fact that parallelism is present with imaging findings in
similar human psychiatric disorders59-63 renders the dog an
interesting natural model.
The use of 99mTc-ECD has also been described in epileptic
dogs in the interictal phase and decreased perfusion in the
subcortical region (a region that comprises a large part of the
thalamus) was reported.64 This finding is of potential signifi-
cance as the role of the thalamus has been described as
causative, that is, involved in the initiation or propagation of
seizures.65,66 The thalamic hypofunction has also been
explained as a consequence of corticothalamic diaschisis.65
To increase resolution and allow further delineation of sub-
cortical subdivisions a micro-SPECT system (HiSPECT) has
PET and SPECT imaging in veterinary medicine
been tested, based on multipinhole collimation on a conven-
tional triple-head gamma camera rendering a resolution of
2.5 mm (HiSPECT, Bioscan, France).67 The same system was
successfully used in cats to evaluate feline rCBF and the effect of
anesthetics.68,69
Neuroreceptor Imaging
Neuroreceptor imaging is used in dogs to investigate the
pathophysiology of behavioral disorders and also to provide a
means to predict the effectiveness of psychopharmacological
therapy. Imaging using radioligands for the serotonin-2A
receptor (with 123I-R91150), the serotonin transporter, and
the dopamine transporter (with 123I-2β-carboxymethoxy-3
β-[4-iodophenyl]tropane and 123I-N-[3-fluoropropyl]-2β-
carbomethoxy-3β-[4-iodophenyl]nortropane) has been
reported in dogs for diagnostic purposes in behavioral
disorders and for the evaluation of medicinal therapy
(Fig. 6).57,70-76 A disturbed serotonergic system was
demonstrated in impulsive-aggressive dogs, dogs with
anxiety disorders, and compulsive dogs. Next to a deficient
serotonergic system, an imbalanced dopaminergic system
was found in compulsive dogs. These imaging findings
again resemble those found in similar human disorders.77-
83
These studies can also guide the decision on which drug
is best suited and are also helpful in monitoring therapeutic
effectiveness.71,75 This could be the key to a patient-
Figure 6 Fused dorsal plane SPECT and MR images acquired following injection of 123I-β-CIT in a dog. Top row of images
depicts activity in the raphe nuclei (small arrows) area (the small “tail”) where the serotonin transporters are located. The
bottom row demonstrates uptake in the basal ganglia (large arrow), where high densities of dopamine transporters are
found. CIT, carbomethoxy-3 β-(4-iodophenyltropane).
53
tailored treatment protocol. In addition, in cats, imaging
of the serotonin-2A receptor has been reported using the
aforementioned tracer and the HiSPECT system.84,69
Orthopedics
The indication for a bone scan is usually lameness or pain
of an unknown origin because clinical or radiographic
examination is equivocal or when the temperament of the
animal precludes clinical examination. Most bone scans in
veterinary medicine are planar studies. SPECT imaging
can reveal lesions that remain undetected on planar
imaging (eg, spinal and pelvic lesions) and provide a
better topographic overview of the suspected region.
SPECT imaging of the canine elbow joint is an excellent
example of the latter characteristic. Most cases of forelimb
lameness are owing to elbow disease. Elbow dysplasia is
the most commonly encountered diagnosis and may affect
different anatomical structures within the joint. On planar
images, it is often impossible to attribute increased uptake
in the elbow joint to a specific anatomical structure. The
limited resolution and the small size of the elbow hamper
differentiation of the anatomical sites, especially when
multiple areas within the joint are affected. Anatomical
landmarks are definitely identified by conventional
SPECT. The micro-SPECT system (HiSPECT, Bioscan,
54
Figure 7 (A) Ventral planar images acquired 3 hours following injection of 99mTc-MDP in a lame dog. There is asymetrical
uptake associated with the elbows, with the left elbow being more intense. Further localization of the increased uptake
within the joint is not possible. (B) HiSPECT images display increased uptake in the medial epicondylar region of the distal
humerus, suggestive for flexor enthesopathy.
France) has superior resolution compared with conven-
tional SPECT and has been used to evaluate normal and
diseased canine elbows (Fig. 7).85,86 This micro-SPECT
system with multipinhole collimation on conventional
gamma camera heads allows adjustment of the gantry
opening for larger animals as opposed to the dedicated
rodent microsystems. A limitation of this system is the
narrow range of the radius of rotation to ascertain optimal
resolution, restricting the skeletal areas that can be
investigated to the elbow and lower forelimb and to the
stifle and lower hindlimb in dogs. Another major draw-
back is that the expense of the collimators and the
dedicated reconstruction software hamper implementa-
tion in the classic veterinary setting. Recently, resolution
recovery software has been commercialized, which may
counter the aforementioned limitations of the HiSPECT
system and offer an interesting alternative, as it allows the
use of a conventional system for investigation of all regions
of the body.
In summary, PET and SPECT imaging in veterinary medi-
cine is gaining in popularity for clinical and research applica-
tions. Challenges that veterinarians face with respect to access to
necessary equipment and infrastructure to support companion
animal imaging programs can be met in part by establishing
collaborations with human imaging facilities. Spontaneous
diseases in dogs and cats offer a unique opportunity to gather
A.K. LeBlanc and K. Peremans
data that could support the development and commercializa-
tion of novel PET imaging agents for human patients.
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