FDG

11.1.1 Radiopharmaceutical

• [¹⁸F]Fluoro-2-deoxy-2-d-glucose, also known as:
  • [¹⁸F]Fluorodeoxyglucose
  • [¹⁸F]FDG
  • FDG

11.1.2 Uptake mechanism / biology of the tracer

[¹⁸F]FDG is a glucose analogue which is taken up by living cells via cell membrane glucose transporters and subsequently phosphorylated with hexokinase inside most cells. [¹⁸F]FDG has been proposed for imaging infection/inflammation, because it has been seen at sites of infection/inflammation during routine [¹⁸F]FDG imaging of cancer patients. Further studies showed that cells involved in infection and inflammation, especially neutrophils and the monocyte/macrophage family, are able to express high levels of glucose transporters, especially GLUT1 and GLUT3, and increased hexokinase activity [351].

11.1.3 Indications

Major indications:

• Sarcoidosis;
• Peripheral bone osteomyelitis (non-postoperative, non-diabetic foot);
• Suspected spinal infection (spondylodiscitis or vertebral osteomyelitis, non- postoperative);
• Evaluation of fever of unknown origin (FUO), including true FUO (defined according to the criteria of Durack and Street) [352]. postoperative fever and recurrent sepsis, immunodeficiency (both induced and acquired) related FUO, neutropenic fever, and isolated acute-phase inflammatory markers;
• Evaluation of metastatic infection and of high-risk patients with bacteraemia;
• Suspicion of endocarditis;
• Primary evaluation of vasculitis (e.g. giant cell arteritis);
• Evaluation and follow-up of malignant otitis externa
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• Therapy follow-up in all of the above-mentioned indications.

Other well-described applications, but without sufficient evidence-base for formal indication:

• Evaluation of potentially infected liver and kidney cysts in polycystic disease;
• Evaluation of vascular prosthesis infections;
• Suspected infection of intravascular devices, pacemakers, and catheters;
• AIDS-associated opportunistic infections, associated tumours, and Castleman’s disease;
• Assessment of metabolic activity in tuberculosis lesions;
• Assessment of organ involvement in fungal infections;

Therapy follow-up in above mentioned indications.
To date, it is unclear if [¹⁸F]FDG imaging offers any significant advantage over radiolabelled white blood cell imaging in the following indications:

• Diabetic foot infections;
• Joint prosthesis infections;
• Inflammatory bowel diseases.

11.1.4 Contra-indications

• Pregnancy is a relative contra-indication.
• It is not recommended to interrupt breast feeding [3].

11.1.5 Clinical performances

The technique is similar to the oncological indications of [¹⁸F]FDG PET/CT, and the reader is referred to the EANM procedure guidelines for tumour imaging 2.0 the UK Royal College of Radiologists evidence-based use of PET/CT, and the review by Vaidyanathan S. et al. [61,178,353].

11.1.6 Activities to administer

The suggested activities are:

• [¹⁸F]FDG in adults: 2.5-5.0 MBq/kg; 175-350 MBq

In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity to administer is 26 MBq.

11.1.7 Dosimetry

The effective dose for [¹⁸F]FDG is 19 µSv/MBq [3]. The organ with the highest absorbed dose is the urinary bladder wall: 130 µGy/MBq.

The range in effective dose for [¹⁸F]FDG is: 3.3-6.7 mSv per procedure.

The radiation exposure related to a CT scan carried out as part of an [¹⁸F]FDG PET/CT study depends on the intended use of the CT study and may differ from patient to patient.

Caveat: “Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

11.1.8 Interpretation criteria/major pitfalls

Visual analysis:

PET images are visually analysed by looking for increased FDG uptake and taking into consideration the pattern (focal, linear, diffuse), intensity, and relationship to areas of physiologic distribution and blood pool activity. PET information is compared with morphological information obtained by CT [354].

• Presence of potential causes of false-negative results should be taken into account (lesion size, low metabolic rate, hyperglycaemia, lesions masked by adjacent high physiological uptake, concomitant drug use interfering with uptake, such as ongoing steroid therapy) and potential causes of false-positive results (injection artefacts, contamination, reconstruction artefacts from attenuation correction, pathological uptake not related to infection or inflammation).
• Care should also be taken to exclude attenuation artifacts.  The PET data are corrected for attenuation using a (low-dose) CT scan. There is a high chance of attenuation artefacts resulting in false positive results when metallic material, implants or other structures with high density on CT are present. Assessment of both attenuation-corrected and non-attenuation-corrected images is recommended.
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Semi-quantitative analysis:

• The standardized uptake value (SUV) has not been validated in inflammation and infection. Therefore, the SUV should be used with caution in clinical practice. There are no general criteria published for inflammatory and infectious disorders. Most research articles have defined interpretation criteria for the purposes of the study. Some authors have reported specific interpretation criteria that can be used, although no definitive consensus has been agreed.

11.1.9 Patient preparation

See the EANM procedure guidelines for tumour imaging 2.0 [61].

It has been advocated that high serum glucose levels may interfere with the targeting of inflammatory and infectious sites due to competitive inhibition of FDG uptake by D-glucose [355].

 However, recent studies demonstrated that neither diabetes nor hyperglycaemia at the time of the study have a significant impact on the false-negative rate in infection and inflammation imaging [356].

This in contrast to tumour imaging, for which reduced uptake has been observed. Although efforts should be made to decrease blood glucose to a normal level if the study is indicated in those with usually unstable or poorly controlled diabetes, hyperglycaemia should not represent an absolute contraindication for performing the study [357].  

To reduce the physiologic FDG uptake in the myocardium a low carbohydrate diet is recommended for 48hrs together with a fasting time of approximately 12hrs before the scan. The administration of Heparin (50 IU/kg ) in addiction to low-carbohydrate diet and fasting may achieve a complete suppression of myocardial FDG uptake in 86% of the patients [358]. 

Delaying the commencement of steroid treatment till after the scan is strongly recommended. The use of steroid treatment can result in a false-negative scan, especially in giant cell arteritis and other systemic vasculitides [359].

If this is not possible or if the patient is already under steroid treatment, then scan under the lowest amount possible.  An exception is when the indication for the [¹⁸F]FDG-PET/CT is to assess disease activity under medication.

Because the effect of antibiotics on [¹⁸F]FDG uptake is unknown, it is important to be aware of ongoing antibiotic treatment, but no general recommendation on withdrawal can be stated.

11.1.10 Methods

The detailed recommendations are available in the EANMM/SNMMI Guidelines for[¹⁸F]FDG-PET/CT Use in Inflammation and Infection  [360].