WHY PET-CT?
CT has been the cornerstone of oncologic imaging for over 20 years but lacks the ability to show differences in physiology. PET has incomparable abilities to determine the metabolic activity of tissues but needs the assistance of higher-resolution, anatomic information that it cannot provide. CT is the easiest and the highest-resolution tomographic modality to integrate into PET imaging. The combination of the two offers the best of both the worlds in an integrated data set and thus improves diagnostic accuracy and localization of many lesions.
Characteristic of malignant cells:
- Malignant cells undergo change in their bio-chemical character which are enhanced rate of glucose metabolism.
- There is an increased number of cell surface-glucose transporter proteins (such as Glut-1 and Glut-3).
- Increased intracellular enzyme levels of hexokinase and phosphofructokinase that promote glycolysis.
- This enhanced glycolytic rate of malignant cells facilitates their detection utilizing 18F-Fluorodeoxyglucose (a glucose analog) for PET imaging.
- The most common glucose transport protein expressed on the tumor cell membrane is Glut-1, which is insulin independent. Studies have shown that FDG uptake is also determined by the number of viable tumor cells within a lesion (tumor-cell density). Non-tumoral tissue such as necrotic and fibrotic tissue have reduce tracer uptake. Increased cell proliferation in tumors (determined by the mitotic rate) also results in increased glucose utilization. Tumor hypoxia will also increase FDG uptake, hypoxia-inducible factor-1-alfa that up-regulates Glut-1 receptors, concluding that FDG accumulation within a tumor is related to a complex interaction between the cellular energy demand and the tumoral micro-environment.
- Once inside the cell, FDG is phosphorylated by hexokinase into FDG-6-phosphate. FDG-6-phosphate does not enter into further metabolism and accumulates intra-cellularly. Reduced levels of glucose-6-phosphatase (an enzyme which metabolizes FDG-6-phosphatase) within tumor cells compared to normal cells permits longer intra-cellular retention of FDG-6-phosphate. The signal derived from tumors represents FDG uptake throughout the lesion.
- FDG is not a cancer-specific agent, and it’s uptake has been described in a number of inflammatory lesions including granulomatous lesions e.g. sarcoid, tuberculosis, fungal infection, and abscess. The accumulation is probably related to a markedly increased rate of glycolysis within activated inflammatory cells.
Point to be noted for diabetic patients
Hyperglycemia and hyperinsulinemia are very important considerations when preparing a patient for a PET study with FDG. High blood levels of glucose will compete with FDG for uptake by the tumor. High levels of insulin will push FDG, along with glucose, into skeletal muscle and myocardium, increasing the image background and decreasing the availability of the radioactive glucose tracer for uptake by the tumor. Optimal imaging conditions can usually be achieved in euglycemic patients with a 6- to 8-hour fast. This fasting is essential for the quality of the test; altered tracer bio-distribution caused by ingestion of even a small meal shortly before a FDG injection can impair the visualization of malignant lesions.
For diabetic patients, the situation is more complex. Several protocols are used by different PET centers to optimize the chances of a good study. A non–insulin-dependent diabetic can be studied early in the morning after an overnight fast if his or her early morning, fasting blood sugars routinely are below 150 – 180 mg/dL.
Bone marrow activation is a major issue in the oncology population because many of the patients are receiving Granulocyte colony stimulating factors or have rebounding bone marrow after a course of chemotherapy. PET usually has very high sensitivity for splenic or osseous metastases, but in a patient who has received GcSF, the marrow and spleen show greatly increased activity that can obscure such lesions. Similar, though usually less intense, uptake can be seen in patients with anemia or those recovering from chemotherapy. In general, PET should be delayed for at least 1 week after administration of short-acting cytokines and up to 3 weeks after administration of long-acting cytokines or chemotherapy.
Because of these and other challenges, referring physicians should provide clinical information with the request for a PET scan to assist the interpreting physician in providing the most accurate information possible in patients.
Some of the important factors include:
- Type of malignancy, date of diagnosis, and location of the lesion (even if it has been resected)
- Recent chemotherapy or anemia
- Recent cytokine therapy
- Inflammatory or infectious processes
- Radiation therapy, which can be a source of inflammation
- Recent surgery, which can cause linear uptake along the incision
- Granulomatous disease
- Claustrophobia or anxiety
Purpose that it serves:
- Detection of occult primary tumor site in patients presenting with metastatic disease.
- Initial staging (primarily to assess resectability).
- Restaging after neoadjuvant chemotherapy and/or radiation.
- Assessment of treatment response following definitive chemoradiation.
- Delineation of gross tumor volume in patients receiving radiation therapy.
- Detection of residual or recurrent cancer when serum tumor marker is elevated.
- Follow-up or surveillance patients with cancer when conventional studies (e.g., CT or bone scan) are equivocal or suspicious.
For optimal scan results PET-CT Scan should be scheduled:
- 1 week post biopsy/GcSF administration
- 1 month post chemotherapy/surgery
- 3 months post radiotherapy
Dr. Arun Gera, Senior Consultant & Coordinator, Dept of Nuclear Medicine, Dharamshila Narayana Superspeciality Hospital, Delhi