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Combined PET/CT : Clinical Applications342
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F-FDG PET also has a role in the assessment of prognosis and treatment in lung cancer
patients. It is specially recommended in assessing early response (13). PET-CT has also shown
to be useful in radiotherapy treatment planning.
Colorectal Carcinoma
Colorectal carcinoma is the third most common malignancy in both men and women and is
the third leading cause of all cancer deaths. Colonoscopy and biopsy form the corner stones in
the diagnosis of colorectal carcinoma. Preoperative staging with imaging modalities is usually
limited because the extent of the disease can be evaluated during surgery and most patients will
benefit from colectomy to prevent intestinal obstruction. Although the sensitivity of 18F-FDG
PET for the preoperative diagnosis of colorectal carcinoma is high, in practice it has no important
role, since surgical diagnosis and staging will be needed for all patients (Figure 5). Even for
detecting local lymph node involvement 18F-FDG PET and PET-CT are reported to have a low
sensitivity of 29% (14). 18F-FDG PET is superior to CT for the identification of liver metastases
(Figure 6). Metastases to the peritoneum, mesentery and lymph nodes are commonly missed on
CT, and the differentiation of postsurgical changes from local tumor recurrence is not accurate
(15). 18F-FDG PET has also been investigated for evaluation of treatment response following
preoperative chemoradiation, where SUVs fall from 5.9 to 2.4 (16) and regional
chemoembolization therapy.
Figure 5: Projection PET image showing focal areas of intense 18F-FDG uptake in ascending
colon in a patient of colonic cancer.
Combined PET/CT : Clinical Applications 343
Figure 6: CT, PET and PET-CT images showing focal areas of intense FDG uptake in liver
suggestive of liver metastases from colon cancer
Recurrent colorectal cancers are usually confined to a single site, mostly liver and surgery in
these cases may serve as a potentially curable therapeutic option. Presence of extra-hepatic
disease is a poor prognostic finding and is also considered as a contraindication for hepatic
resection. Till now CT is commonly used to localize the site of possible recurrence, which has
lower sensitivity and specificity (Figure 7). Higher accuracy has been reported for 18F-FDG PET
(92%) than CT portography (80%) or CT alone (78%) (14). CT portography is an invasive
procedure and costlier than 18F-FDG PET. Concurrent PET-CT imaging permits a definite diagnosis
and may be especially important in the abdomen and pelvis. PET-CT imaging increases the
accuracy and certainty of locating lesions (Figure 5). PET/CT is superior to contrast enhanced
CT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases,
and local recurrence at the site of the initial colorectal surgery (17).
Figure 7: CT, PET and PET-CT images showing intense FDG uptake in rectum in a patient of
suspected local recurrence of rectosigmoid colon cancer.
Combined PET/CT : Clinical Applications344
False positive results are seen in patients with fistulas, abscesses, diverticulitis and adenomas.
False negative results are seen due to normal physiological activity in the intestine, which can
obscure intestinal lesions with PET alone. However with PET-CT there is improvement in
detection of intestinal lesions. Microscopic lymph node metastasis can cause false negative
results in up to 20% of patients when compared with post surgery histological findings.
Breast Cancer
Breast cancer is the most common malignancy in women. Mammography is the most
commonly used imaging technique for the diagnosis of primary tumor but has lower sensitivity
in women with dense breasts and breast implants (18). MR imaging and US have limited value
in differentiating benign abnormalities from malignancies (19). 18F-FDG PET and PET-CT play
a very important role in the work up of breast cancer (20). Though, dense breasts show increased
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F-FDG uptake as compared to non-dense breast tissue, it does not effect the detection of the
primary tumor in patients with dense breasts (Figure 8) (21).
Figure 8: CT, PET and PET-CT images showing intense 18F-FDG uptake in right breast suggestive
of primary breast cancer.
Figure 9: CT, PET and PET-CT images showing intense FDG uptake right breast suggestive of
primary breast cancer. In addition there is another area of FDG uptake in right axilla suggestive
of axillary lymph node metastasis.
Combined PET/CT : Clinical Applications 345
Metastasis to axillary lymph nodes is one of the most important prognostic factors in breast
cancer patients. Even though FDG-PET can detect axillary node involvement, it has been shown
to have limitations in detecting lymph node metastasis when compared to sentinel lymph node
biopsy (22). However, a clearly positive 18F-FDG PET in selected patients with a high risk of
nodal metastases carries high positive predictive value and may identify patients with evidence
of nodal metastases (Figure 9). This could indicate the need for standard axillary nodal dissection
and therapeutic approaches, rather than SLN biopsy.
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F-FDG PET has been reported to detect metabolic changes in breast cancer as early as 8
days after initiation of chemotherapy (23). Locoregional and distant metastasis occurs in up to
35% of patients of breast cancer within 10 years of initial surgery (24). Whole body PET/ PETCT has emerged as a sensitive and noninvasive technique in the management of breast cancer. A
sensitivity of 93% and specificity of 79% with 18F-FDG PET has been reported in detecting
metastatic disease (25). However, in detecting bone metastasis variable degrees of sensitivity and
specificity have been reported (26). Non-detectable lesions on 18F-FDG PET were sclerotic or
mixed sclerotic / osteolytic radiologically. PET has a limited role in detecting bone metastasis in
the skull due to high uptake in the brain. The combination of 18F-FDG PET scan and bone scan
can be used for better sensitivity and specificity. False positives are seen with benign breast
diseases like abscesses, tuberculosis, and fungal infections, which can be metabolically active.
Post surgical inflammatory changes can also cause false positive results due to higher FDG
uptake. False negatives are seen in patients with carcinoma-in-situ, low-grade tumors and well
differentiated ductal and lobular breast cancers. In addition, smaller lesions (<1 cm) can be
missed by PET/PET-CT images as they have lower SUVs due to partial volume effect. Axillary
lymph nodes with micrometastsis and macrometastsis (smaller number of tumor cells) usually
have false negative results.
Lymphoma
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F-FDG PET / PET-CT is emerging as a powerful imaging modality for the diagnosis,
staging, and treatment monitoring in lymphomas (27). All histological types of NHL can be
successfully imaged with 18F-FDG PET, with no significant difference in standardized uptake
values (SUV) among different sites and grades of disease both in HD and aggressive NHL (27).
For some subtypes of low-grade lymphoma (small lymphocytic and probably mantle cell
lymphoma) the routine use of PET is still an issue that needs further evaluation. 18F-FDG PET/
PET-CT can detect more lesions than CT and may lead to a change in the stage in up to 15% of
patients (Figure 10) (28). In cases of extranodal lymphomas, 18F-FDG PET has an important role
in guiding other investigations like biopsy and histopathological examination. Another major
advantage of 18F-FDG PET is that, it is a whole body imaging method.
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F-FDG PET provides an excellent tool for accurate assessment of the response during and
at the end of treatment and during follow up for detection of recurrence (Figure 11). PET has a
high predictive value for differentiation between active tumor and fibrosis (29). It has been
assessed for first-line induction therapy as well as for new and more aggressive treatment
Combined PET/CT : Clinical Applications346
Figure 10: CT, PET and PET-CT images showing intense 18F-FDG uptake in cervical, mediastinal
abdominal and pelvis lymph nodes suggestive of advanced disease.
protocols. CT or other morphological imaging techniques cannot differentiate between fibrosis
and recurrence. Though in earlier times gallium-67 scintigraphy was used in patients with recurrent
disease, it is less sensitive in intra abdominal and low-grade lymphoma (30). Low-resolution
images also made these studies difficult to interpret. 18F-FDG PET is very efficient and the
precise fusion of morphologic and metabolic imaging data using hybrid PET-CT systems is
useful for the management of a residual mass after therapy of lymphoma (30).
False positives are seen with benign inflammatory/infective diseases and due to inflammatory
changes post surgery/radiotherapy/chemotherapy. It is advisable to wait for 6-8 weeks after these
interventions. Postchemotherapy bone marrow stimulation can result in high SUV in bone marrow
and cause difficulty in interpretation. False negatives are seen with low-grade lymphomas (small
lymphocytic and probably mantle cell lymphoma), follicular lymphomas and CNS lymphomas.
Lymph nodes with smaller number of tumor cells especially after completion of chemotherapy
can cause false negative results in up to 20% of cases.
Head and Neck Cancer
Head and neck cancers are the most common in India. Unfortunately, most of the patients (as
high as 45%) present with regional nodes or even distant metastases at the time of initial
diagnosis. Patients with cervical lymph node metastasis from an unknown primary tumor present
as a big diagnostic dilemma. 18F-FDG-PET can be a valuable tool in this subset of patients with
an occult primary tumor in the head and neck region, as early identification of the primary tumor
may allow more accurate tumor staging and targeted radiotherapy (31). Other imaging studies
rarely contribute valuable information, and it is extremely unlikely that these will identify a
Combined PET/CT : Clinical Applications 347
A)
(A) (B) (C)
Figure 11: PET images (before chemotherapy) showing intense 18F-FDG uptake in cervical,
mediastinal lymph nodes and stomach suggestive of active disease (A). PET image obtained after
2 cycles of chemotherapy show significant improvement in 18F-FDG uptake in cervical and
mediastinal lymph nodes. No stomach activity is noted in post chemotherapy scan (B). PET image
obtained after 6 cycles of chemotherapy show complete resolution of the disease (C).
primary tumor that cannot be detected by PET. Lymph node metastasis in head and neck tumors
is associated with poor prognosis. Accurate pre-therapy lymph node staging is essential for
therapeutic planning. Conventional imaging modalities like CT/MRI detect only fewer than 50%
of involved nodes due to their dependence on the size criteria and might result in unnecessary
neck surgery (32). The sensitivity and specificity of 18F-FDG PET varies from 71% to 91% and
88% to 100% in detecting metastatic lymph nodes (Figure 12) (33). 18F-FDG PET can demonstrate
up to 30% of previously undetected primary head and neck tumors (34). After radiation therapy
and surgery, distortion of the normal anatomy limits the utility of MRI and CT to demonstrate
residual or recurrent disease. 18F-FDG PET has a better sensitivity of 88-100% Vs 72-92% and a
better specificity of 75-100% vs. 50-57% as compared with CT and MRI in detecting recurrence
at the primary site (35). 18F-FDG PET / PET-CT is also more sensitive and specific in detecting
residual and recurrent lymph node metastasis (36).
PET has a very important role in identifying the response to treatment. The sensitivity and
specificity of 18F-FDG PET for residual cancer 1-2 weeks after treatment are 90% and 83%
respectively in patients with head and neck cancer (37). A positive scan obtained at least 6
weeks after end of therapy suggests residual disease, unless there are clinical signs of inflammation/
infection to explain the abnormalities on PET.
Combined PET/CT : Clinical Applications348
Figure 12: CT, PET and PET-CT images showing intense 18F-FDG uptake in cervical lymph
nodes and larynx suggestive of local recurrence with lymph nodes metastases.
The role of 18F-FDG PET in thyroid cancer should also be stressed. Diffuse thyroid 18F-FDG
uptake is usually an indicator of chronic thyroiditis (38). In contrast, focal 18F-FDG activity in
the thyroid gland has been associated with malignancy (39).
substitute for
123
I or
131
I whole-body scintigraphy in the evaluation of metastatic or recurrent
thyroid cancer. However, in patients with increased thyroglobulin levels and negative
118
F-FDG PET may not be a
123
I or
131
scan especially under TSH stimulation, the utility of 18F-FDG PET scan has been confirmed in
several studies, and the sensitivity of 18F-FDG PET in detecting metastases in these cases ranges
from 71% to 94% (40). In patients with medullary thyroid cancer somatostatin receptor
scintigraphy may be more sensitive than 18F-FDG PET. However, when fluorine-18
dihydroxyphenylalanine or 18F-DOPA is used the results are very impressive (41). False positives
are seen with benign inflammatory/infective diseases. Head and neck cancers are usually lowgrade tumors and cause false negative results. Lymph nodes with low-grade tumors or lymph
nodes with smaller number of tumor cells can cause false negative results in up to 40% of cases.
I
The role of PET/CT in intensity modulated head and neck radiotherapy has been studied,
where it can selectively target and intensify the treatment of head and neck cancer while reducing
critical normal tissue doses (42). Lack of anatomic information in PET images is particularly
critical in these patients because of close proximity of various anatomic structures and the high
frequency of normal variants in 18F-FDG uptake in the head and neck.
Malignant Melanoma
Unlike in other malignancies, there is no defined role for 18F-FDG PET in the initial diagnosis
of melanoma (43). PET is of limited use in patients with early-stage disease without nodal or
distant metastases (stage I–II), because sentinel node biopsy is much more sensitive in detecting
microscopic lymph node metastases (44). However, melanoma metastasizes very widely to skin,
Combined PET/CT : Clinical Applications 349
muscle, bone, bowel, myocardium, omentum, leptomeninges, mesentry etc. 18F-FDG PET shows
a high tumor-to-background ratio and is therefore useful in this situation as it can highlight
metastases at unusual sites that are easily missed with conventional imaging modalities (45). The
accuracy of PET in detecting melanoma metastasis ranges from 81-100% (46). 18F-FDG PET is
also more accurate than conventional imaging in restaging and follow-up.
Gastric and Esophageal Cancer
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F-FDG PET is sensitive for the detection of primary gastric and esophageal cancers (47).
However, the identification of regional nodal metastases has been restricted due to the small
volume of disease in some lymph nodes. But still 18F-FDG is more specific than CT and
endoscopic US for loco-regional lymph node metastasis (Figure 13). PET is reliable in
differentiating resectable and non-resectable disease and avoids many unnecessary surgeries. 18FFDG-PET is more accurate than conventional imaging with CT and US in evaluating response to
radiation therapy and chemotherapy. PET/PET-CT has false positive results in patients with
inflammatory/infective diseases of esophagus and stomach. False negatives are seen in cases of
LNs that are very close to the primary lesion due to a very high uptake in primary and early
nodal disease.
Figure 13: CT, PET and PET-CT images showing intense 18F-FDG uptake in middle 1/3 of
oesophagus in patient of oesophageal cancer.
Bone Tumors
Osteosarcoma is the most common primary bone malignancy in childhood. Diagnostic imaging
has played a major role in the evaluation of patients with cancers of bone and soft tissue. MRI is
used to define the local extent of osteosarcoma in bone and soft tissue. However, signal
abnormalities caused by peritumoral edema can result in an overestimation of tumor extension.
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F-FDG PET may play an important role in determining the metabolic rates of osteosarcoma,
guiding biopsy, detecting local recurrence in amputation stumps, evaluating patients with suspected
metastatic disease, monitoring response to therapy and assessing for prognosis and differentiating
viable sarcoma from post treatment changes (Figure 14) (48).
Combined PET/CT : Clinical Applications350
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F-FDG uptake in osteosarcoma has a good correlation with histological grading or tumor
aggressiveness. 18F-FDG PET scan also help in guiding biopsy to the most active tumor metabolic
site. 18F-FDG PET shows marrow involvement directly in patients with multiple myeloma,
unlike bone scans that show marrow involvement indirectly by imaging cortical bone osteoblastic
reaction to the marrow tumor. This results in early detection of marrow involvement as compared
to bone scan and other conventional imaging modalities. PET is also useful in assessing the
response to treatment (49) (Figure 15).
Figure 14: CT, PET and PET-CT coronal images showing intense 18F-FDG uptake in right
elbow joint and adjoining soft tissue (primary) in a case osteosarcoma. Note multiple focal areas
of intense 18F-FDG uptake in right axillary lymph nodes, both lungs, liver and other soft
tissues.
False positives are seen with acute and chronic osteomyelitis, fractures, trauma, benign bone
tumors and bone marrow stimulation. False negatives are seen in cases of low grade primary
bone tumors and lymph nodes, which are very close to primary bone tumors due to very high
uptake in primary and early nodal disease.
Ovarian cancer
Ovarian carcinoma is one of the most difficult of all gynecologic cancers to control and is at
an advanced stage at the time of presentation in two third of patients. In patients with ovarian
cancer, primary lesion localization is difficult with PET. 18F-FDG PET has high sensitivity and
specificity in identifying patients with recurrent tumor (50) and lymph node metastases. However
like other imaging modalities it has a limited role in micrometastases and very small lesions
(51). A negative PET scan during the follow- up period after the primary treatment predicts
longer relapse free interval than a positive PET scan. 18F-FDG PET has also been found to be
cost-effective in the therapeutic management of patients with ovarian cancer (52). The combination
of all three modalities was considered to be the method of choice for the imaging assessment of
Combined PET/CT : Clinical Applications 351
Pre-Chemotherapy Post-Chemotherapy
Figure 15: PET and PET-CT images (Pre and Post chemotherapy PET-CT scan) showing intense
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F-FDG uptake in left knee joint and adjoining soft tissue (Primary) in a case osteosarcoma. Post
chemotherapy shows significant fall in FDG uptake suggestive of good response to chemotherapy.
asymptomatic adenexal masses for malignancy. Similarly, the addition of 18F-FDG PET to CT
increases accuracy in staging ovarian cancer (53). When combined, conventional imaging and
PET result in highest diagnostic yield for detecting the sites of recurrent disease (Figure-16).
Figure 16: CT, PET and PET-CT images showing intense FDG uptake in pelvic, abdominal and
mediastinal lymph nodes suggestive of recurrent disease in a patient of ovarian cancer with rising
tumor markers.
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