PET-CT in Orthopaedic Oncology

PET-CT combines metabolic and anatomic information in one study, and it is increasingly used in orthopaedic oncology for staging, treatment response and the detection of recurrence. What it measures is glucose metabolism, not malignancy directly.

The Warburg effect. Malignant cells preferentially use glycolysis for energy, even in the presence of oxygen, and this increased glucose uptake is the basis of the scan. FDG (fluorodeoxyglucose) is a glucose analogue that cells take up but cannot metabolise, so it becomes trapped. Higher-grade, more aggressive tumours typically have higher glucose metabolism and FDG uptake.

The protocol. Fasting, the glucose check and the fixed uptake period matter because SUV depends on blood glucose and on uptake time, as the next section sets out.

Staging and biopsy. PET-CT assesses the whole body for metastases, and it can guide biopsy to the metabolically active areas of a tumour. What it adds in each tumour is set out in the next section.

Response. PET-CT can assess treatment response earlier than anatomic imaging, usually after neoadjuvant chemotherapy and before surgery. A decrease in SUVmax of more than 40% between the pre- and post-treatment scans indicates metabolic response, and this may predict histological response and prognosis in sarcomas. PERCIST measures SUL peak rather than SUVmax and sets its boundaries at a 30% change:

Recurrence. PET-CT can detect local recurrence and distant metastases in sarcoma surveillance, and it is more sensitive than conventional imaging for some recurrences. False positives from post-surgical change and inflammation limit its specificity, and routine PET-CT surveillance after sarcoma resection is not supported by high-level evidence; CT chest plus local MRI remain standard. It is best reserved for problem-solving (equivocal recurrence, rising tumour markers, the symptomatic patient) rather than scheduled follow-up, balancing radiation dose and false positives.

Infection is a separate argument. Oncology is where FDG-PET is best established in orthopaedics. The second major indication, infection, is covered on the Labelled White Cell Scintigraphy page, because the two indications are judged against different comparators and reach different conclusions:

• Spinal osteomyelitis - FDG is the radionuclide study of choice, with a high negative predictive value. Labelled leucocyte imaging is explicitly not recommended for the spine, where infected vertebrae are often photopenic and read as false negatives.
• Periprosthetic joint infection - the opposite verdict. FDG cannot reliably separate infection from aseptic loosening, because both provoke an intense inflammatory reaction, and combined labelled leucocyte/marrow imaging remains the more specific test.
• Diabetic foot osteomyelitis - FDG-PET and Tc-99m HMPAO leucocyte imaging offer comparable, and the highest available, specificity.

The fact that unifies them is that FDG marks activated macrophages, and therefore inflammation, not infection and not malignancy specifically. That explains its strength in the spine, its weakness around a loose prosthesis, and post-surgical false positives, which settle only after roughly three to four months.

Osteosarcoma. Beyond skip lesions and distant metastases at staging, a decrease in SUV after chemotherapy correlates with histological necrosis, which is a good prognostic factor. For lung metastases a dedicated CT chest is still needed, and it remains superior for small nodules.

Soft tissue sarcoma. High-grade lesions are FDG-avid, and an SUVmax greater than 6 predicts higher grade. Low-grade sarcomas such as well-differentiated liposarcoma and low-grade fibromyxoid sarcoma may have minimal uptake. PET helps detect nodal involvement in selected subtypes.

Chondrosarcoma. PET-CT is used for grade assessment and to look for dedifferentiation. The overlap between enchondroma and grade 1 chondrosarcoma (atypical cartilaginous tumour) is the central unresolved problem: very low SUVmax favours benign and high SUVmax favours grade 2/3, but the benign-to-G1 boundary remains unreliable on PET alone, and histology, MRI and clinical correlation are mandatory.

Metastatic disease. PET-CT surveys the whole body and searches for an unknown primary, complementary to the bone scan.

Uptake is not malignancy. PET-CT cannot reliably differentiate benign from malignant in all cases, because infection, inflammation and healing all take up FDG, as do recent radiotherapy and arthritis. Always correlate uptake with the history and with CT/MRI morphology, and meet suspected infection with clinical correlation and follow-up.

False negatives. A negative scan does not clear a lesion. PET has limited sensitivity for low-grade tumours, where MRI is better; lesions under 1 cm may be missed through resolution limits; and hyperglycaemia lowers uptake, so control the glucose and repeat if needed.

Definition. The standardised uptake value is a semi-quantitative, dimensionless ratio that normalises the FDG activity concentration measured in a region to the injected dose and the patient's size: SUV = tissue activity concentration (e.g. MBq/mL) divided by [injected dose (MBq) / body weight (g)]. In effect it asks how much brighter the lesion is than it would be if the tracer were spread evenly through the body. It is a stand-in for metabolic rate, not a direct measurement of malignancy.

Reading the number. Higher SUV generally correlates with higher grade, and although the threshold varies, an SUVmax greater than 2.5 is often used as a cut-off.

Why a single threshold cannot be transferred. SUVmax is not standardised across scanners, and absolute SUV is not comparable between centres or time points because it depends on:

• Blood glucose - high glucose competes with FDG and lowers tumour SUV
• Uptake time - SUV keeps rising for an hour or more, so the scan delay must be fixed
• Body habitus and lean mass - fat dilutes weight-based SUV, hence SUL
• Scanner model and reconstruction algorithm
• Partial-volume effect - lesions below roughly twice the scanner resolution falsely read low

A single number such as 2.5 therefore cannot reliably separate benign from malignant, or low grade from high grade, across all centres. PERCIST exists because absolute SUV is not transferable between time points unless conditions are tightly controlled: it mandates identical conditions and uses the normal liver (or blood pool) as an internal reference for response. The general physics of PET acquisition is developed in the nuclear-medicine-orthopaedics topic.

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Tissues that are normally hot. The brain is an obligate glucose user, so it is the most FDG-avid normal tissue, which limits the assessment of intracranial lesions. Myocardial uptake varies with the fasting state; a prolonged fast and a low-carbohydrate, high-fat preparation can suppress it. The liver and blood pool show moderate, relatively uniform uptake, and the normal liver is the standard internal background against which lesions and response are judged.

Excretion. Unlike natural glucose, which is reabsorbed, FDG is renally excreted, so the kidneys, ureters and bladder are intensely active. That urinary activity can obscure lesions in the pelvis and bony pelvis, and hydration and bladder emptying before imaging help.

Variable and avoidable uptake. This is the source of many false positives. Skeletal muscle takes up FDG if recently exercised, hence rest before and after injection; the larynx and vocal cords do so if the patient is talking, hence "avoid talking"; bowel uptake is variable.

Brown fat. Brown adipose tissue gives symmetric supraclavicular, paraspinal and mediastinal uptake in fat density (CT-negative). Keeping the patient warm and beta-blockade or a benzodiazepine reduce it, and it should not be mistaken for nodal disease.

Bone marrow. Marrow shows mild physiological uptake that is diffusely increased after G-CSF or marrow recovery from chemotherapy. This reactive uptake can both mimic and mask marrow disease in the very sarcoma patients being imaged, so correlate before calling marrow metastases.

Prognostic or predictive? Whether baseline or interim SUV should change treatment (risk-adapted chemotherapy) is unproven. Studies show an association with histological necrosis and survival, but no randomised trial has demonstrated that altering therapy on PET findings improves outcomes, and PET-guided treatment escalation remains investigational.