Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5255_Библиотеки_им_академика_М_И_Перельмана
.pdf
Combined PET/CT : Clinical Applications352
False positives are seen with inflammatory/infective abdominal diseases. Physiological activity
in gastrointestinal tract can also cause misinterpretation. False negatives are due to low uptake
in mucinous cyst adenocarcinoma. It also has limited value for detection of micrometastases and
very small lesions.
Cervical Cancer
Invasive cancer of the cervix is the second most common genital malignancy in women,
worldwide. Many studies have evaluated the role of 18F-FDG PET in primary staging of cervical
cancer and showed a variable sensitivity and specificity (54). Recurrence occurs in 30% of cases,
despite advancement in the management of cervical cancer. Conventional imaging modalities are
often unable to differentiate recurrence from fibrosis/necrosis. 18F-FDG PET is known to play an
important role in detecting recurrence (Figure 17). False positives are seen with infected fibroids,
cervicitis and other inflammatory/infective pathologies. Increased 18F-FDG uptake is also noted
during menstrual cycle. False negatives are seen during detection of primary cervical cancer in
early stages and disease activity in pelvic LNs, which are very close to urinary bladder (due to
very high uptake in urinary bladder).
Figure 17: CT, PET and PET-CT images showing intense 18F-FDG uptake in cervix in a patient of
cervical cancer suggestive of recurrent disease.
Gastrointestinal Tumors
Pancreatic Cancer
Pancreatic cancer is the fourth most common cause of cancer death. Early diagnosis is
essential for potentially curative resection like in other malignancies. 18F-FDG PET has been
extensively evaluated for pancreatic cancer (55). 18F-FDG PET in pancreatic cancer is mainly
indicated for staging by detecting CT-occult metastases, detecting recurrence, monitoring therapy
and for the diagnosis in patients with suspected pancreatic cancer in equivocal CT or non-
Combined PET/CT : Clinical Applications 353
diagnostic FNAC (56). An important aspect in pancreatic imaging is differentiation of pancreatic
cancer and benign lesions. 18F-FDG PET, being a functional study, has been shown to be an
effective imaging modality in this regard. In the present scenario, 18F-FDG PET is considered as
a complementary study in pancreatic cancer, especially when CT is non-diagnostic (Figure 18).
18
F-FDG PET may reveal unsuspected metastases to the liver, bones and lungs, thereby changing
the management protocol. 18F-FDG PET has been shown to be an effective imaging modality in
detecting distant metastasis in patients with pancreatic cancer (57). 18F-FDG PET is also useful
in evaluation of treatment effect, monitoring after surgery and detection of recurrent pancreatic
cancers. PET/PET-CT has false positive results in patients with acute and chronic pancreatitis
and pancreatic cyst. False-negative findings are noted in patients with insulin-dependent
Figure 18: CT, PET and PET-CT coronal and axial images showing intense 18F-FDG uptake
in pancreatic mass, regional lymph nodes and liver suggestive of pancreatic cancer with
metastases.
Hepatocellular Carcinoma (HCC)
The role of 18F-FDG PET is limited in HCC. It is mainly indicated in patients with moderately
or poorly differentiated HCC, tumors >5 cm, or with markedly elevated AFP levels (58). Owing
to the variable activity of the enzyme glucose-6-phosphatase in the hepatocytes in patiens with
HCC, there is a varying degree of accumulation of 18F-FDG. Consequently, 18F-FDG PET imaging
can have three different patterns, namely higher uptake, equivocal uptake and lower uptake,
Combined PET/CT : Clinical Applications354
compared to normal liver background. Recently, 11C-Acetate has been studied as a radiotracer for
PET imaging in patients with HCC (59) for the detection of well-differentiated tumours. Liver
abscess and inflammatory/infective liver diseases leads to false positive results.
False Negatives are due to variable 18F-FDG uptake due to glucose-6-phosphatase enzyme in
the hepatocytes in liver diseases. Liver malignancies may show higher, equivocal and lower
uptake, compared to normal liver background.
Gastrointestinal stromal tumors (GIST)
GISTs are a subset of mesenchymal tumors of the gastrointestinal tract, occuring in the
stomach in 70% of cases. CT scanning is the imaging modality of choice in GISTs, which can
locate a mass lesion, contiguous organ invasion and distant metastases. 18F-FDG PET in GISTs
is being used widely since the introduction of imatinib mesylate. As 18F-FDG PET is a functional
imaging study, it may be expected to be useful in rapid evaluation of response to imatinib. It may
show significant drop in 18F-FDG uptake early after imatinib therapy, while on conventional
anatomical imaging, tumor size may remain constant for an indefinite period of time. 18F-FDG
PET improves staging, accurately separates responders from non-responders in an early stage,
and is helpful during follow-up. PET/PET-CT has false positive results in patients with
inflammatory/infective abdominal diseases. Physiological activity in gastrointestinal tract can
also cause misinterpretation.
Urological Malignancies
Prostate Cancer
Prostate cancer is the most common malignancy in men and the second most common cause
of death, after lung cancer in the United States. The most effective screening tools are digital
rectal examination (DRE) and serum prostate specific antigen (PSA) monitoring. The role of 18FFDG PET in prostate cancer localized within the gland is limited owing to low metabolic
behavior shown by this tumor and urinary excretion of FDG (60). It is also not very useful in
differentiating hypertrophy from cancer, a major obstacle in the diagnosis of prostate cancer
(60,61). However, FDG uptake correlates well with PSA levels as a measure of tumor size,
advanced tumor or PSA relapse (61,62). 18F-FDG PET has a limited role in detecting soft-tissue
metastasis to pelvic lymph nodes, owing to the urinary excretion of FDG through kidneys and
low glucose metabolism by tumor cells (61,63). In osseous metastasis too, the use of 18F-FDG
PET is limited (61). However, 18F-FDG PET can be useful when conventional imaging methods
like bone scanning, show equivocal or negative results, especially in progressively metastatic
tumors.
Bladder Tumors
The role of 18F-FDG PET in bladder cancer is very limited and little work has been done in
Combined PET/CT : Clinical Applications 355
this field (64). Urinary excretion of FDG and streak artifacts from excreted tracer in the bladder
has contributed to the limited value of 18F-FDG PET in bladder cancer (61). However, it can be
useful in advanced cancer diagnosis. Avid uptake of choline has been found in bladder cancer
with virtual absence of urinary radioactivity (65) and could be useful in this regard.
Renal Cancer
As the excretory route of FDG is mainly renal, the role of 18F-FDG PET is chiefly in
detecting recurrence and metastatic renal cancer (Figure 19) (61,66). Diuresis has been suggested
to increase the contrast between the tumor and background renal tissue (67). Studies have shown
a complimentary role of 18F-FDG PET to the conventional imaging methods, in detecting distant
metastasis (68).
Figure 19: CT, PET and PET-CT images showing intense 18F-FDG uptake in right renal bed
suggestive of recurrent disease in a patient of renal cell cancer.
Testicular Cancer
Among urological tumors, 18F-FDG PET is most useful in testicular cancers, especially in
defining recurrent disease in residual masses and in patients with raised markers. 18F-FDG PET
has been evaluated for its role in testicular tumor recurrence or relapse (69). It has been used to
predict treatment response in testicular cancer (70).
Neuroendocrine tumors
Functional imaging has a great role in neuroendocrine tumors as it targets the molecular
characteristics of endocrine tumors. The role of PET in neuroendocrine tumors is continuously
and rapidly increasing as a complementary and valuable diagnostic tool, particularly when other
imaging modalities have failed (71). 18F-FDG is used most commonly. Other positron-emitting
radionuclides, being studied, are 11C-Hydroxyephedrine, 11C-Epinephrine, 11C-5-hydroxytryptophan
and 18F-DOPA, 68Ga-DOTA-TOC etc. (72).
Combined PET/CT : Clinical Applications356
Pheochromocytomas and Paragangliomas
18
F-FDG PET has been used in phaeochromocytoma as an adjunct to other imaging modalities.
It helps in localizing the majority of pheochromocytomas as most of these tumors accumulate
18
F-FDG. However, 18F-FDG PET has been described to have lower sensitivity and also lower
specificity (due to accumulation of glucose by a variety of other neoplastic and non-neoplastic
processes) (72). Therefore, at present, it is generally recommended in cases where other
investigations fail to show results (Figure 20) (73).
Figure 20: CT, PET and PET-CT images showing intense 18F-FDG uptake in left adrenal, multiple
thoracic vertebrae and mediastinal lymph nodes in a patient of malignant pheochromocytoma.
18
F-DOPA whole-body PET has been studied and found to be highly sensitive and specific
for detection of pheochromocytomas and paragangliomas and monitoring the response to therapy
(74). 18F-DOPA PET also helps in detecting metastasis from malignant pheochromocytomas,
especially when used after negative MIBG study (75). 68Ga-DOTA-TOC is a new PET
radiopharmaceutical and has shown encouraging results in the management of neuroendocrine
tumours (Figure 21).
Combined PET/CT : Clinical Applications 357
Figure 21: Ga-68-DOTA-TOC scan: CT, PET and PET-CT images showing multiple areas of
intense DOTA-TOC uptake in stomach and duodenum in a patient of gastrinoma.
Carcinoid Tumors
Carcinoid tumors are difficult to diagnose in earlier stages because of their small size and
multiplicity. CT is mainly used for characterizing and staging of the tumor. Somatostatin receptor
scintigraphy (SRS) is the functional imaging study used for detection and staging of carcinoid
tumours. Unfortunately, the role of 18F-FDG PET is limited in carcinoid tumors due to their low
proliferative activity and high differentiation rate (76). Therefore, other PET radiotracers like
18
F-DOPA and 11C-labeled 5-HTP have been studied, which are specifically directed towards the
carcinoid tumors (72,77).
Adrenocortical Tumors
Tumors of the adrenal cortex may present with Cushing’s syndrome, feminization, virilization,
hyperaldosteronism (hypertension), hypoglycemia, mixed hormone excess syndrome or sometimes,
with no recognizable features. The diagnosis depends upon the level of hormonal metabolites in
blood/urine and localization of adrenal mass on CT/MRI. Functional studies, e.g. adrenocortical
scintigraphy, mostly use radiopharmaceuticals, which are analogs of cholesterol, thereby, acting
as a substrate for adrenal steroid hormone synthesis. 18F-FDG PET is a useful functional imaging
modality for detection of primary adrenocortical cancer and metastatic lesions (78). 18F-FDG
PET has been shown to have excellent diagnostic performance (sensitivity 93% and specificity
90%) in differentiating adrenal lesions detected on CT or MRI in patients with known malignancies
(78). 18F-FDG PET has the additional advantage of evaluating primary lesions as well as metastases
(79). Recently, 11C-Etomidate and 11C-metomidate have been used effectively as tracers in PET
imaging to distinguish adrenocortical tumor from metastatic cancer based on targeting of specific
enzyme (11ß-hydroxylase) involved in cortisol and aldosterone synthesis (80). However, this
does not allow differentiation of benign from malignant adrenocortical lesions.
Combined PET/CT : Clinical Applications358
Pituitary Tumors
Pituitary tumors are common and an early diagnosis is a must for a favorable therapeutic
outcome. Clinical features are mainly due to local effects of the mass in the cranium and distant
endocrine manifestations. MRI is preferred over CT scan for the pituitary because of better
visualization of soft tissues and vascular structures around the gland. However, CT scanning is
better to visualize bony structures and calcification. A lot of radiotracers have been used to
evaluate the role of PET in pituitary tumors but none have come in widespread use, MRI
remaining the imaging modality of choice in these tumors (72). 11C-methionine and 11C-tyrosine
have been used on the basis of mechanism of protein synthesis, while 11C-deprenyl, 11C-raclopride,
11
C-methylspiperone and 18F-fluoroethylspiperone have been used based on the expression of
receptors (72,81). These tracers have been shown to discriminate between different types of
pituitary adenomas, or between viable tumour tissue and fibrosis, bleeding, necrosis, and in
distinguishing recurrent tumour from postoperative changes, identifying parasellar tumors, and
assessing response to treatment. False positives are seen in patients with infective/inflammatory
diseases.
Brain Tumors
The role of 18F-FDG PET in brain tumors is chiefly in gliomas, the most frequently occurring
primary brain tumors (82). 18F-FDG PET is basically a measure of glucose uptake and mainly
used for grading tumors, distinguishing tumor from necrosis, or other post-radiation effects
(82,83). Increased 18F-FDG uptake has been correlated with tumor grade, tumor cell density,
biological aggressiveness, and survival of patients in primary as well as recurrent gliomas (83).
However, there are diagnostic limitations of 18F-FDG PET for imaging brain tumors, mainly due
to difficulty in characterizing tumors in the brain, owing to high glucose uptake of normal brain
tissue. (Figure 22) (84).
Figure 22: CT, PET and PET-CT images showing intense 18F-FDG uptake in left temporal brain
tumor suggestive of recurrent disease.
Combined PET/CT : Clinical Applications 359
New radiotracers like 11C-methionine (11C-MET), 11C-tyrosine, 18F-fluoro-tyrosine, 18Ffluoroethyl-tyrosine (18F-FET), 8-cyclopentyl-3-(3-18F-fluoropropyl)-1-propylxanthine (18F-CPFPX)
and 18F-fluoro-thymidine (18F-FLT) have been studied for PET imaging in brain tumors (82,83).
These new agents are different from the traditional 18F-FDG in that the normal brain uptake of
these compounds is lower. Several studies have proved 11C-MET PET as a good imaging
technique for brain tumors (85), particularly for low-grade gliomas. Other newer radiotracers
have also been used to characterize primary brain tumors and have a promising role in the future.
18
F-FLT PET and 18F-CPFPX PET have been specifically used to image cellular proliferation in
brain tumors (86). 18F-FET PET has also been evaluated in characterizing brain tumors (87).
As with other tumours, false positives are seen in infective/inflammatory diseases, while
false negatives are seen with low and moderate grade primary brain tumors due to physiological
18
F-FDG uptake in brain.
PET in Cardiology
Positron emission tomography (PET) is an investigative tool that has allowed unprecedented
in vivo quantification of physiologic processes including myocardial perfusion and metabolism.
The ability to label biomolecules with positron-emitting radioisotopes, without disturbing their
physiological properties, offers the opportunity to prove and quantify coronary blood flow,
myocardial metabolism, and the alterations that occur with disease states. PET has been developed
as a clinical imaging tool for the quantitative assessment of myocardial perfusion and for the
characterization of tissue viability in patients with advanced CAD. Cardiac PET with 18F- FDG is
very helpful in selection of patients with coronary artery disease and left ventricular dysfunction
who would benefit from coronary artery revascularization. Many authors consider cardiac PET
as a gold standard in this particular application. The extent of viable myocardium is an important
factor for both prognosis and prediction of outcome after revascularization in patients with
ischemic cardiomyopathy and chronic left ventricular dysfunction (88). PET imaging shows
metabolism in viable myocardial segments, most metabolically viable segments on PET imaging
recovering function after revascularization (227). 13N- ammonia is also being used for PET
imaging but this compound has limitations due to its short half-life. Another PET tracer, rubidium82, has shown good results in the detection of myocardial perfusion abnormalities (90).
A number of recent studies provide some insight on the potential of PET/CT in the assessment
of various types of vasculitis and metabolic diseases (91,92,93). A number of studies have
evaluated the value of 18F-FDG in visualizing and assessing focal and systemic vasculitis (92,93).
Though not used routinely for the detection of any vascular disease, 18F-FDG with CT can aid in
assessing the presence and stability of plaques (94). Other indications of PET in cardiology
include the evaluation of cardiomyopathies, postcardiac transplant evaluation and cardiac receptor
evaluation for the regulation of cardiovascular functions.
Many pathophysiological processes take place in the nerve terminals, synaptic clefts, and
postsynaptic sites in the heart. These processes are altered in many diseases such as heart failure,
Combined PET/CT : Clinical Applications360
diabetic autonomic neuropathy, idiopathic ventricular tachycardia, arrhythmogenic right ventricular
cardiomyopathy, heart transplantation, drug-induced cardiotoxicity, and dysautonomias (95).
Cardiac neurotransmission imaging can be obtained using PET. The most commonly used PET
radiopharmaceuticals for imaging presynaptic activity are 18F-fluorodopamine, 11Chydroxyphedrine, and 11C-ephidrine. Postsynaptic agents include 11C-(4-(3-t-butylamino-2hydroxypropoxylbenzimidazol-1) CGP, and 11C-carazolol.
PET in Neurology
PET imaging of the brain allows non-invasive quantification of cerebral blood flow,
metabolism, and receptor binding. Epilepsy, brain tumors, dementias and movement disorders
are the main indications of PET in neurology.
Epilepsy
Complex partial seizures in a significant proportion of patients remain uncontrolled despite
optimal medical therapy. Surgical removal of epileptogenic foci in partial seizures such as
intractable temporal lobe epilepsy results in significant control of the seizures and the quality of
life (96). MRI is able to identify the source of the seizure in the majority of patients. However,
20–30% of potential surgical candidates with focal epilepsy have normal MRI. PET study reveals
an increase in glucose metabolism and cerebral blood flow in the region of the epileptogenic
focus during the ictal period (97). Post-ictally, hyperperfusion gradually returns to baseline, but
the glucose metabolism remains elevated for another 24–48 hours after the seizure (98). Interictal
PET shows decreased glucose metabolism and blood flow in the epileptogenic focus.
Brain tumors
Tumour cells, especially of higher histological grades, typically have increased metabolic
and mitotic rates compared with normal brain tissue. 18F-FDG PET can provide important
prognostic information as increased glucose metabolism correlates with higher histological grades
and shorter survival period (99). It can also detect transformation of low-grade glioma into a
high-grade variety (100). The information obtained may influence the choice of the therapeutic
approach. 18F-FDG PET also provides an objective subclinical evidence of response to treatment
(101). One to two week post-treatment interval is recommended prior to performing 18F-FDG
PET to accurately assess response to treatment and to avoid false positive studies due to transient
increase in glucose uptake (101).
Alzheimer’s Disease and Related Disorders
18
F-FDG PET has been used extensively to study dementia and it may be an effective tool for
early diagnosis and differentiation of various types of dementia. Alzheimer’s disease (AD) is the
most common cause of dementia in the elderly. PET imaging can differentiate AD from other
forms of dementia. In patients with AD, there is a decrease in glucose metabolism in the
Combined PET/CT : Clinical Applications 361
temporoparietal lobes that is not evident in patients with other forms of dementia. A new
PETtracer, 2-(1-{6-[(2-[18F] fluoroethyle)(methyle) amino]-2naphthyl} ethylidene) malononitrile
(18F-FDDNP), has been used to target amyloid saline plaques and neurofibrillary tangles in AD
(102). This tracer shows prolonged retention in affected areas of the brain. Disorders, such as
head injury, frontal lobe dementia, and Huntington’s disease, can also be assessed with high
accuracy using PET.
Movement Disorders
Several radionuclide-labeled neuroreceptors and neurotransmitters have shown excellent results
with PET. These PET radiopharmaceuticals have great potential for the assessment of movement
disorders. 2-Carbomethoxy-3-(4-chlorophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) and
18
F-DOPA both allow assessment of the integrity of presynaptic dopaminergic neurons (103).
These compounds are able to diagnose Parkinson’s disease and other diseases effectively. 11Craclopride positron emission tomography also provides an indirect marker of changes in levels of
dopamine in the synaptic cleft.
Neuropharmacology
PET receptor ligand studies offer the opportunity to use an in vivo technique to study the
pharmacodynamics and biodistribution of new agents and to ensure they target the organs or
compartments of interest. There have been recent advances in the use of PET imaging to measure
the pharmacokinetic and pharmacodynamic effects of drugs of abuse on the human brain (104).
Functional brain mapping using PET is increasingly being used to reliably and accurately identify
speech and sensory-motor areas to minimize postoperative morbidity.
References
1. Mochizuki T, Tsukamoto E, Kuge Y, et al. FDG uptake and glucose transporter subtype expressions
in experimental tumor and inflammation models. J Nucl Med 2001; 42: 1551-1555.
2. Delbeke D. Oncological applications of FDG PET imaging: Brain tumors, colorectal cancer, lymphoma,
and melanoma. J Nucl Med 1999; 40: 591-603.
3. Larson SM. Cancer or inflammation? A holy grail for nuclear medicine. J Nucl Med 1994; 35: 1653-
1655.
4. Mavi A, Lakhani P, Zhuang H, Gupta NC, Alavi A. Fluorodeoxyglucose-PET in characterizing solitary
pulmonary nodules, assessing pleural diseases, and the initial staging, restaging, therapy planning,
and monitoring response of lung cancer. Radiol Clin North Am 2005; 43: 1-21.
5. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission
tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001; 285:
914-924.
6. Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18F-FDG PET for the evaluation of
pulmonary nodules. J Nucl Med 2002; 43: 871-875.
7. Kim BT, Kim Y, Lee KS, et al. Localized form of bronchoalveolar carcinoma: FDG PET findings. Am
J Roentgenol 1997; 170: 935-939.
Соседние файлы в папке Библиотека им академика М.И. Перельмана