# FDG PET/CT: Principles, Interpretation, and Oncologic Applications

## Introduction

**Fluorine-18 fluorodeoxyglucose (FDG) PET/CT** is the most widely used molecular imaging technique in oncology. By combining metabolic information from PET with anatomic detail from CT, FDG PET/CT has transformed cancer staging, treatment response assessment, and surveillance. Understanding the physics, normal biodistribution, and common pitfalls is essential for accurate interpretation.

## Physics and Radiopharmaceutical Principles

### FDG Metabolism

FDG is a **glucose analog** labeled with fluorine-18, which has a half-life of 110 minutes. FDG is transported into cells via **GLUT transporters** (especially GLUT-1) and phosphorylated by hexokinase. Unlike glucose, **FDG-6-phosphate cannot undergo further glycolysis** and becomes trapped intracellularly. Malignant cells demonstrate increased glycolysis (the **Warburg effect**), resulting in preferential FDG accumulation. PET detects the **511 keV annihilation photons** produced when the positron emitted by F-18 encounters an electron.

### Patient Preparation

Patients must fast for **4-6 hours** prior to injection to minimize insulin-mediated skeletal muscle uptake. Blood glucose should be **less than 200 mg/dL** (ideally below 150 mg/dL), since elevated glucose competes with FDG for uptake. Strenuous exercise should be avoided for 24 hours before the exam to minimize muscle uptake. The typical dose is **10-15 mCi** IV FDG, followed by a **60-minute** uptake period of quiet rest in a warm room before scanning. Patients with **diabetes** require special management, and insulin should not be given within 4 hours of FDG injection.

### Image Acquisition and Reconstruction

PET/CT scanners acquire both datasets in a single session. The CT component is used for **attenuation correction** and anatomic localization. Images are reconstructed using iterative algorithms (OSEM) and displayed in axial, coronal, and sagittal planes as PET, CT, and fused images. Maximum intensity projection (MIP) images provide a global overview.

## Normal Biodistribution and Variants

### Expected FDG Uptake

The **brain** shows intense physiologic uptake because it is a glucose-obligate organ. **Myocardial** uptake is variable depending on fasting state and metabolic substrate. The **liver** shows moderate homogeneous uptake and serves as the internal reference standard. The **kidneys and bladder** show uptake because FDG is excreted via the urinary tract, with intense bladder activity. **Tonsils and lymphoid tissue** demonstrate symmetric mild-to-moderate uptake as a normal finding. **GI tract** uptake, particularly in the colon, is a frequent normal variant.

### Common Pitfalls and Artifacts

**Brown fat activation** produces symmetric bilateral uptake in the supraclavicular, paravertebral, and mediastinal regions, more commonly in young, thin patients and cold environments. **Muscle uptake** can occur in the vocal cords after talking during the uptake period or diffusely from exercise or insulin. **Inflammatory and infectious processes** cause false positives because FDG is not cancer-specific: granulomatous disease, post-surgical changes, and infections all accumulate FDG. **Metallic artifacts** from dense implants cause CT attenuation correction artifacts appearing as focal hot spots.

## Standardized Uptake Value (SUV)

**SUV** is a semi-quantitative measure of FDG uptake normalized to injected dose and patient body weight. **SUVmax**, the maximum voxel value within a region of interest, is most commonly reported. An SUVmax greater than 2.5 is generally considered suspicious for malignancy, though this threshold varies by tumor type and location. Factors affecting SUV include blood glucose level, uptake time, body composition, and reconstruction parameters. **SUVmax should not be used in isolation** but always correlated with morphologic CT findings.

## Oncologic Applications

### Staging

For **lung cancer**, PET/CT is the standard of care for staging non-small cell lung cancer, detecting mediastinal nodal and distant metastases with a high negative predictive value for negative mediastinal nodes. For **lymphoma**, PET/CT is essential for staging Hodgkin and aggressive non-Hodgkin lymphoma using Ann Arbor staging with the Lugano modification. In **melanoma**, it is useful for stage III-IV disease but less sensitive for small or superficial lesions. For **head and neck cancer**, it detects primary tumors, nodal metastases, and synchronous primaries. PET/CT is also used for staging in **esophageal and gastric cancer** and for detecting hepatic metastases and recurrence in **colorectal cancer**.

### Treatment Response Assessment

| Deauville Score | FDG Uptake | Interpretation |
|----------------|-----------|----------------|
| 1 | No uptake above background | Complete metabolic response |
| 2 | Uptake <= mediastinum | Complete metabolic response |
| 3 | Uptake > mediastinum but <= liver | Complete metabolic response (most protocols) |
| 4 | Uptake moderately > liver | Residual disease (treatment dependent) |
| 5 | Markedly increased uptake or new lesions | Residual/progressive disease |

The **Deauville criteria (5-point scale)** is the standard for lymphoma response assessment. Score 1 indicates no uptake above background, score 2 indicates uptake at or below the mediastinum, score 3 indicates uptake above the mediastinum but at or below the liver, score 4 indicates uptake moderately greater than the liver, and score 5 indicates markedly increased uptake or new lesions. **PERCIST criteria** for solid tumors are based on percentage change in SULpeak (lean body mass-corrected). Interim PET during chemotherapy predicts outcomes in Hodgkin lymphoma.

### Surveillance and Recurrence Detection

PET/CT is valuable when tumor markers are rising with negative conventional imaging, for detection of recurrence in colorectal cancer, head and neck cancer, and melanoma, and for differentiating post-treatment changes from residual or recurrent disease.

## Tumors with Low or Variable FDG Avidity

Several tumor types demonstrate low or variable FDG uptake. **Hepatocellular carcinoma** may be FDG-negative when well-differentiated due to glucose-6-phosphatase activity. **Prostate cancer** generally has low FDG avidity, making PSMA PET preferred. **Renal cell carcinoma** shows variable uptake, and urinary excretion can obscure lesions. **Mucinous tumors** have low cellularity that reduces uptake. **Lepidic-predominant adenocarcinoma** (formerly bronchoalveolar carcinoma) is often FDG-negative. **Low-grade neuroendocrine tumors** are better evaluated with gallium-68 DOTATATE PET.

## Clinical Pearls

FDG PET/CT is **not cancer-specific**: inflammatory and infectious processes cause false positives, and some malignancies are FDG-negative. Patient preparation is critical, as fasting, glucose control, and a warm environment reduce artifacts and false findings. The **Deauville 5-point scale** is the standard for lymphoma response assessment. SUVmax is a useful metric but must always be interpreted in the context of clinical history and CT morphology.

## References

1. FDG PET/CT in Oncology: Current Status and Future Directions. *Radiology*. 2020;296(2):231-244.
2. Barrington SF, Mikhaeel NG. PET Scans for Staging and Restaging in Diffuse Large B-Cell and Follicular Lymphoma. *Curr Hematol Malig Rep*. 2016;11(3):185-195.
3. ACR Appropriateness Criteria: Staging and Follow-up of Non-Small Cell Lung Cancer. *J Am Coll Radiol*. 2021;18(11S):S342-S362.
4. Boellaard R, et al. FDG PET/CT: EANM Procedure Guidelines for Tumour Imaging. *Eur J Nucl Med Mol Imaging*. 2015;42(2):328-354.