CT/PET In Oncology: The road ahead

Dr Neelendu Purandhare

Fused PET-CT is a recent imaging technique that combines the anatomic detail provided by CT with metabolic information provided by PET.

The first dedicated PET-CT scan was installed at the Tata Memorial Hospital in 2004. It combines the 16 slice ability of a CT scan and the resolution of a dedicated PET crystal.

More and more cancers are now being imaged by PET-CT in the initial diagnostic workup and during the follow up stage. PET-CT will surely in the near future be accepted as a standard of care for most if not all cancers.

Pathophysiology of PET imaging

Metabolism in a biological cell is the first to change before the cell undergoes changes like dysplasia, metaplasia or cancer. This is followed by structural changes.

PET scan detects the disease at metabolic level. CT and MRI detect disease at morphological level. Majority of cancer cells demonstrate high level of glycolysis and hence preferentially use glucose as substrate for their metabolism. In view of this, the uptake of radiolabelled glucose (FDG) is four to six times the normal cell and increases with time. Cancer cells concentrate glucose due to following reasons: Increase in membrane glucose transporter proteins and GLUT.

Increase in some enzymes such as hexokinase, which are responsible for phosphorylation of glucose to glucose -6-phosphate. FDG is transported to tumor cells in a similar way to glucose and is phosphorylated to FDG-6-phosphate. FDG-6-phosphate is not efficiently metabolised further and therefore accumulates within the cell. Thus, FDG is metabolically trapped in the malignant cell. This process of metabolic trapping of FDG in the cell constitutes the basis of imaging.

But Why Annihilation reaction

Positrons released from decaying F-18 component of FDG annihilate with electrons to release two coincident 511 kev photons that are detected by scintillation crystals.

Basic unit of a PET scanner is crystal:
BGO BISMUTH GERMINATE
GSO GADOLINIUM
OXY-ORTHOSILICATE
LSO LEUTETIUM
OXY-ORTHOSILICATE

Each has its own advantages and drawbacks.

Why PET-CT has an edge over PET

PET-CT reduces image acquisition times, thus we have more patient throughput. Conventional, whole body PET takes about one hour. Around 50 per cent of this time is taken by the transmission scan. As PET-CT utilises CT data for attenuation correction, whole body imaging time is reduced by 50 per cent.

It provides better patient co-operation due to reduced scan times, improved lesion localisation and characterisation due to CT and reduction in false positive rates.

SUV

• The intensity of FDG uptake is estimated by the standardised uptake value (SUV).
• It is a semi-quantitative estimate of FDG uptake.
• Does SUV value, by itself, convey anything?
• The prognostic value of FDG has been investigated by many.
• Median survival decreased with increasing SUV.

1)Median survival time -
24.6 months for SUV <10.
11.4 months for SUV >10.

2)Two year survival rate-
68 % for SUV > 9.
96 % for SUV <9.

• One can not put an objective universal cutoff value.
• It just tells us that in a proven cancer, higher FDG uptake means a more aggressive lesion.

FDG is not the perfect cancer imaging agent

• It reflects only glucose metabolism.
• Depends on nutritional state.
• There is some uptake in normal tissues.
• There can be uptake in pathologies other than cancer.
• No uptake in certain cancers.
• But, so far it is the best that we have!

Some cancers show over expression of GLUT receptors and hence are FDG avid. These are lung, colorectal, oesophagus, head and neck, breast, melanoma, lymphoma (most), and ovary.

Variable uptake of FDG

• Thyroid
• HCC
• Renal
• Urinary Bladder
• Sarcomas
• Testicular
• Neuroendocrine
• Prostate cancers may not be FDG avid at all

Role in staging For T staging

CT and MRI still remain the modalities of choice for local tumor invasion and extent. In some cases, PET-CT can be useful in differentiating atelectasis from tumor in lung cancer and to predict chest wall invasion.

In nodal staging, it performs better than it does for T staging. CT is still relied upon for nodal staging, though it has its own limitations. The same age-old problem remains. Inability to differentiate between enlarged nodes due to benign and malignant causes inability to identify tumor in normal-sized nodes.

PET-CT ideally, according to literature, has better sensitivity, specificity and accuracy to detect locoregional nodes. It does pick up nodes which otherwise would be normal by CT criteria. It picks nodes at unexpected sites. Though they may be false positives, it at least alerts the clinicians to observe or perform a biopsy.

Metastatic disease

Presence of distant metastases is classified as stage IV disease. It precludes a patient from the possibility of curative surgical resection and is prescribed palliative therapy. An inherent advantage of PET is the use of whole-body scanning, which facilitates the survey of a much larger area than is possible with commonly used radiographic methods.

Role in differentiating post-treatment change from residual/recurrent disease.

In head-neck cancers

• Surgical and radiation changes complicate anatomy.
• Distortion of normal anatomy if patients undergo some form of reconstructive procedure with flaps or grafts.
• Loss of imaging landmarks and symmetry.
• Distinction between post therapy changes and recurrence/residual tumor becomes challenging.

In colorectal cancers

• Loco-regional pelvic recurrence and liver metastases are major sites of relapse after resection of rectal cancer.
• Most patients undergoing abdominoperineal resection develop a fibrotic mass in the presacral operative bed.
• Radiation therapy causes inflammatory reaction in the pelvic tissues and induces thickening of the perirectal fascia.
• These changes may be seen on CT images for many years and may be indistinguishable from tumor recurrence.
• PET-CT has been very useful in differentiating these changes from tumor.

Response evaluation and restaging

• The response can be morphologic or metabolic. Measuring and evaluating the morphologic response to therapy is less than ideal as morphologic response to therapy occurs over several weeks to months. During the interim period, patients with non-responding tumors are treated without benefit. Morphologic evaluation can be inaccurate.
• Drawbacks of using morphologic criteria.
• Reduction of metabolic activity seen on PET correlates with .
• histopathological tumor response and eventually patient survival.

Thus, FDG PET-CT as an oncologic imaging modality has a clear potential to influence treatment decisions and thereby impact patient care.

(Dr Neelendu Purandhare spoke during IRIA)
The writer is Consultant Radiologist, Tata Memorial Hospital, Mumbai