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FDG PET/CT for Infection and Inflammation

By Jim O'Brien, M.Md.Sc., DABR, DABSNM
December 6, 2024 16 min read

FDG PET/CT has become the imaging method of choice for a wide range of infectious and inflammatory disorders because activated leukocytes and macrophages are avid glucose consumers that accumulate F-18 fluorodeoxyglucose (FDG) intensely at sites of active disease.1 The current EANM/SNMMI guideline defines 19 distinct infection and inflammation indications for hybrid FDG PET — from spondylodiskitis and periprosthetic joint infection to prosthetic valve endocarditis, vascular graft infection, and fever of unknown origin.1

But the study is only as good as its preparation and quantification. Patient fasting, cardiac dietary suppression, a controlled uptake period, standardized SUV measurement, and disciplined attention to physiologic pitfalls are what separate a diagnostic FDG PET/CT from an uninterpretable one.126

Introduction

FDG is often thought of as an oncology tracer, but its underlying mechanism — trapping in cells with high glucose demand — makes it equally powerful for imaging infection and inflammation. The first EANM/SNMMI guideline for FDG PET in infection and inflammation appeared in 2013; the version 2.0 guideline published in 2024 reflects a decade of accumulated evidence and now covers 19 evidence-based indications, each with its own protocol points, interpretation criteria, and pitfalls.1

That breadth is exactly why the study demands physics and protocol rigor. The same tracer that lights up a lymphoma will light up normal myocardium, bowel, brown fat, and post-surgical inflammation. Whether an FDG PET/CT answers the clinical question depends on controlling those competing signals through preparation, uptake timing, and standardized quantification — the same discipline a medical physicist applies to any quantitative PET exam.6

This article walks through the FDG mechanism, patient preparation (including the special case of cardiac sarcoidosis), the core technical principles of SUV quantification and dose, the clinical impact across key indications, practical optimization tips, the regulatory framework, and the interpretation pitfalls that most often compromise a study.1267

Topic Explanation

Why FDG images infection and inflammation

F-18 FDG is a glucose analog. It enters cells through the same GLUT membrane transporters as glucose and is phosphorylated by hexokinase to FDG-6-phosphate — but that phosphorylated product cannot proceed through glycolysis and is effectively trapped inside the cell. Because trapping accumulates over time in proportion to glucose metabolic rate, tissues with high glycolytic activity show progressively increasing FDG concentration.16

At sites of infection and inflammation, activated neutrophils, monocytes, macrophages, and lymphocytes sharply upregulate glucose transporter expression and glycolytic flux. The result is intense, localized FDG accumulation that marks active inflammatory and infectious foci — the biological basis for using FDG PET/CT across a broad spectrum of non-oncologic disease.1

Key terms used throughout this article:

  • FDG — F-18 fluorodeoxyglucose, a positron-emitting glucose analog (F-18 physical half-life ~109.8 minutes).
  • Uptake time — the interval between injection and imaging (commonly ~60 minutes) during which FDG distributes and traps.
  • SUV (standardized uptake value) — measured tissue activity concentration normalized to injected activity and body weight.
  • Target-to-background ratio (TBR) — lesion uptake divided by a reference background (e.g., blood pool), used where absolute SUV is confounded.

The breadth of indications

The version 2.0 guideline organizes FDG PET use into infectious and inflammatory categories spanning 19 indications, including: bacteremia and metastatic infection/septic embolism; spondylodiskitis with and without spinal hardware; osteomyelitis in noncomplicated and complicated bone; septic arthritis; diabetic foot infection; periprosthetic joint infection; native and prosthetic valve endocarditis; cardiac implantable electronic device and ventricular assist device infection; vascular graft and endograft infection; infected liver and kidney cysts; invasive fungal infection; tuberculosis and other mycobacterioses; large-vessel vasculitis and polymyalgia rheumatica; and sarcoidosis.19 The unifying theme is a clinical question — is there active infection or inflammation, and where — that anatomic imaging alone often cannot answer.

Preparation is the study

Because physiologic glucose uptake competes with the pathologic signal, preparation determines whether the study is interpretable. For most indications, patients fast at least 4–6 hours to lower and stabilize blood glucose (high serum glucose competitively reduces lesion FDG uptake), then rest during a ~60-minute uptake period before acquisition.6 Cardiac indications are the critical exception, discussed below. For the general quantitative-PET framework these rules derive from, see our overview of FDG PET dose optimization and PET uptake time.

Key Technical Principles

The standardized uptake value

The most common quantitative index is the body-weight SUV, which normalizes the measured tissue activity concentration to the injected activity (decay-corrected to scan time) and body mass :

Worked example. A patient receives and weighs . A suspected infectious focus measures . Assuming tissue density near 1 g/mL:

An SUVmax of ~4 in an appropriate clinical context is consistent with active inflammatory/infectious uptake. But SUV is only meaningful when acquisition is standardized: it varies with uptake time, blood glucose, partial-volume effects in small foci, reconstruction, and scanner calibration — which is why the EANM tumour-imaging guideline exists to harmonize SUV across sites and scanners, and why the same calibration and QC apply to infection imaging.6

Uptake time and decay

Because FDG continues to trap during the uptake period while F-18 decays, both effects must be controlled. F-18 decays exponentially with a physical half-life min:

Over a 60-minute uptake period the remaining fraction of activity is:

so about 68.5% of the injected activity remains at imaging. This is why SUV is always decay-corrected to a reference time and why keeping the uptake time consistent (typically 60 minutes, minimizing variation) is essential for reproducible numbers across scans and across a patient's follow-up.6

Radiation dose

Using the ICRP Publication 128 adult effective-dose coefficient for F-18 FDG of , a typical 370 MBq administration delivers a radiopharmaceutical effective dose of:

The CT component adds a variable dose depending on whether a low-dose attenuation-correction CT or a diagnostic-quality CT is acquired.7 Nuclear medicine procedures remain a modest but non-trivial contributor to overall U.S. medical radiation exposure, so managing that combined dose — matching the CT protocol to the clinical need — is part of the physicist's role in a hybrid PET/CT program.8

Comparison of key indications

The table below summarizes representative indications, the decisive preparation point, and the dominant interpretation pitfall for each, drawn from the guideline and consensus documents.1259

Indication Decisive preparation Dominant pitfall
Prosthetic valve endocarditis Standard fast; consider dietary suppression Post-surgical/inflammatory uptake in first weeks after implant
Cardiac sarcoidosis High-fat, low-carb diet + prolonged fast Incomplete myocardial suppression → false "diffuse" pattern
Periprosthetic joint infection Standard fast Aseptic loosening and normal peri-hardware uptake
Vascular graft / endograft infection Standard fast Low-grade sterile graft incorporation uptake
Large-vessel vasculitis Standard fast; delay after steroids Atherosclerotic uptake; steroids suppressing signal
Fever of unknown origin Standard fast Nonspecific uptake requiring correlation

Endocarditis: a quantified example of value

For infective endocarditis, a meta-analysis of 13 studies and 537 patients reported a pooled FDG PET/CT sensitivity of 76.8% and specificity of 77.9%, rising to a sensitivity of 80.5% for prosthetic valve endocarditis specifically, and identified clinically relevant extracardiac infectious foci in 17% of patients.5 Those numbers explain why FDG PET/CT is now embedded in diagnostic pathways for prosthetic valve endocarditis: it adds sensitivity where the modified Duke criteria are weakest, and its whole-body field of view finds distant septic foci that change management.5

Clinical Impact

FDG PET/CT changes management precisely in the cases where conventional workup stalls — culture-negative infections, hardware where anatomy is ambiguous, and systemic inflammatory disease without a clear source. Its whole-body coverage is a distinctive strength: a single study can localize a primary focus and simultaneously reveal metastatic or extracardiac spread, as in the 17% extracardiac-focus rate seen in endocarditis imaging.5

Cardiac sarcoidosis is the clearest example of preparation determining clinical value. Normal myocardium can consume glucose avidly, so without dietary suppression the scan is uninterpretable. A structured, reinforced high-fat, low-carbohydrate preparation protocol improved adequate myocardial suppression from 78% to 91% of patients in a single-center study, and a prolonged 72-hour high-fat, high-protein, very-low-carbohydrate diet reduced the indeterminate rate substantially compared with shorter preparation.34 The physics lesson is simple: the same acquisition, with and without correct preparation, produces a diagnostic study or a wasted one.

Large-vessel vasculitis and polymyalgia rheumatica illustrate another dimension — FDG PET/CT can map the extent of arterial wall inflammation and guide treatment, with joint EANM/SNMMI procedural recommendations standardizing acquisition and interpretation for these indications.9 Across all of these uses, the study contributes most when it is acquired to a standard that makes its numbers trustworthy, which is where quality control and physics support directly affect patient care.6

Practical Optimization Tips

Standardize acquisition so SUV means something

Consistency is the currency of quantitative PET. To keep SUV comparable within and across patients:6

  • Fix the uptake time near 60 minutes and record it; deviations shift SUV.
  • Verify and document blood glucose before injection; hyperglycemia suppresses lesion uptake.
  • Weigh the patient at the visit rather than using a reported weight (SUV depends on mass).
  • Keep scanner calibration and cross-calibration current with the dose calibrator, and run daily PET QC.
  • Use consistent reconstruction so follow-up SUVs are comparable.

Get cardiac preparation right

For suspected cardiac sarcoidosis, treat dietary preparation as part of the acquisition, not an afterthought:234

  • Provide written, specific diet instructions with accepted and non-accepted meal examples.
  • Target at least two high-fat (>35 g), low-carbohydrate (<3 g) meals the day before, then a 4–12 hour fast; use ~18-hour fasting as an alternative.
  • Reinforce and verify adherence (nursing review of a dietary log) — structured reinforcement measurably improves suppression.

Match the CT to the question

The CT component's dose and diagnostic quality should be chosen deliberately: a low-dose attenuation-correction CT suffices for localization, while a contrast-enhanced diagnostic CT may be warranted when detailed anatomy is needed. Aligning CT technique with the clinical question controls dose without sacrificing information.7

Time imaging around therapy

Steroids and antibiotics suppress the inflammatory signal FDG depends on. Where clinically feasible, imaging before or at a defined interval relative to immunosuppressive therapy improves sensitivity, particularly for vasculitis and sarcoidosis.29

Regulatory Considerations

FDG PET/CT for infection and inflammation sits within the NRC (or Agreement State) framework for medical use of byproduct material and is guided by professional society standards that define how the study should be performed and interpreted.

  • Medical use of byproduct material. F-18 FDG is a byproduct-material radiopharmaceutical administered under 10 CFR Part 35 (or the equivalent Agreement State program), with occupational and public dose limits under 10 CFR Part 20. Dosage determination and recordkeeping requirements apply to each administration.
  • Professional guidelines. The EANM/SNMMI guideline/procedure standard for FDG hybrid PET in infection and inflammation (version 2.0, 2024) is the primary evidence-based reference for indications, protocols, and interpretation.1 The SNMMI-ASNC consensus governs cardiac sarcoidosis preparation and interpretation,2 and the EANM/SNMMI recommendation governs large-vessel vasculitis imaging.9
  • Quantitative standardization. The EANM tumour-imaging guideline (version 2.0) provides the SUV harmonization and QC framework that underpins reliable quantification in any FDG study, including infection imaging.6
  • Dose framework. ICRP Publication 128 provides the radiopharmaceutical dose coefficients used to estimate patient effective dose.7
  • State programs and service areas. DRPS supports PET/CT and nuclear medicine programs across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware; radioactive-material licensing is administered by the NRC or the Agreement State authority (DC and Delaware are direct-NRC). Always confirm requirements with the authority having jurisdiction.

Frequently Asked Questions (FAQs)

Why does FDG accumulate in infection and inflammation, not just tumors?

FDG is a glucose analog taken up through GLUT transporters and phosphorylated by hexokinase to FDG-6-phosphate, which is metabolically trapped. Activated neutrophils, macrophages, and lymphocytes at sites of infection and inflammation strongly upregulate glucose transport and glycolysis, so they accumulate FDG avidly — the basis for using FDG PET/CT well beyond oncology.1

How should a patient be prepared for an FDG PET/CT for infection?

For most indications, patients fast at least 4–6 hours to control blood glucose and minimize physiologic uptake, then rest during a ~60-minute uptake period before imaging. Cardiac indications require additional high-fat, low-carbohydrate dietary suppression of normal myocardial uptake.26

What special preparation does cardiac sarcoidosis imaging need?

Consensus recommends at least two high-fat (>35 g), low-carbohydrate (<3 g) meals the day before the scan followed by a 4–12 hour fast, or about 18 hours of fasting as an alternative. Structured, reinforced protocols substantially improve adequate myocardial suppression.234

Is FDG PET/CT accurate for prosthetic valve endocarditis?

It is a valuable adjunct: a meta-analysis reported ~77% pooled sensitivity and ~78% specificity for infective endocarditis overall, improving to ~80% sensitivity for prosthetic valve endocarditis, and it detected extracardiac infectious foci in ~17% of patients.5

How is FDG uptake quantified?

The standardized uptake value normalizes tissue activity concentration to injected activity and body weight. SUVmax and target-to-background ratios support interpretation, but SUV depends on uptake time, glucose, partial-volume effects, and calibration, so standardized acquisition and QC are essential.6

What is the radiation dose from an FDG PET/CT?

For a typical 370 MBq adult administration, the radiopharmaceutical effective dose is roughly 7 mSv using the ICRP 128 coefficient; the CT component adds a variable additional dose depending on the CT protocol.7

Key Takeaways

  • FDG images infection and inflammation because activated leukocytes and macrophages are avid glucose consumers that trap FDG-6-phosphate.1
  • The EANM/SNMMI version 2.0 guideline defines 19 evidence-based infection and inflammation indications.1
  • Preparation is the study: fasting controls glucose, and cardiac indications require high-fat, low-carbohydrate dietary suppression of normal myocardium.234
  • SUV normalizes tissue activity to injected activity and body weight but is only reliable under standardized uptake time, glucose, and calibration.6
  • FDG PET/CT adds sensitivity for prosthetic valve endocarditis (~80%) and finds extracardiac foci in ~17% of patients.5
  • A typical 370 MBq FDG administration delivers ~7 mSv from the radiopharmaceutical, plus a variable CT contribution.7

Conclusion

FDG PET/CT earns its place across infection and inflammation because a single tracer mechanism — glucose-analog trapping in metabolically active cells — maps active disease that anatomic imaging misses. The version 2.0 EANM/SNMMI guideline formalizes that reach across 19 indications, but the recurring lesson is that the study's value is made or lost in preparation and quantification: fasting and cardiac dietary suppression control the competing physiologic signal, and standardized uptake time, glucose control, and scanner calibration make SUV trustworthy. Handled with that rigor, FDG PET/CT is one of the most versatile problem-solvers in nuclear medicine.126

How DRPS Can Help

Diagnostic Radiation Physics Services (DRPS) supports PET/CT and nuclear medicine programs across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware with PET/CT and nuclear medicine physics, scanner calibration and SUV harmonization, protocol optimization, dose management, and accreditation support — all delivered by board-certified medical physicists.

A dependable FDG PET/CT infection program is built on standardized preparation, verified quantification, and a calibrated scanner. Those are physics deliverables, and they are what make the clinical images worth trusting.

Related Resources

References

  1. Abikhzer G, Treglia G, Pelletier-Galarneau M, et al. EANM/SNMMI guideline/procedure standard for [18F]FDG hybrid PET use in infection and inflammation in adults v2.0. Eur J Nucl Med Mol Imaging. 2024;52(2):510-538. doi:10.1007/s00259-024-06915-3. pubmed.ncbi.nlm.nih.gov
  2. Chareonthaitawee P, Beanlands RS, Chen W, et al. Joint SNMMI-ASNC expert consensus document on the role of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring. J Nucl Cardiol. 2017;24(5):1741-1758. doi:10.1007/s12350-017-0978-9. pubmed.ncbi.nlm.nih.gov
  3. Christopoulos G, Jouni H, Acharya GA, et al. Suppressing physiologic 18-fluorodeoxyglucose uptake in patients undergoing positron emission tomography for cardiac sarcoidosis: the effect of a structured patient preparation protocol. J Nucl Cardiol. 2021;28(2):661-671. doi:10.1007/s12350-019-01746-4. pubmed.ncbi.nlm.nih.gov
  4. Lu Y, Grant C, Xie K, Sweiss NJ. Suppression of myocardial 18F-FDG uptake through prolonged high-fat, high-protein, and very-low-carbohydrate diet before FDG-PET/CT for evaluation of patients with suspected cardiac sarcoidosis. Clin Nucl Med. 2017;42(2):88-94. doi:10.1097/RLU.0000000000001465. pubmed.ncbi.nlm.nih.gov
  5. Mahmood M, Kendi AT, Ajmal S, et al. Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis. J Nucl Cardiol. 2019;26(3):922-935. doi:10.1007/s12350-017-1092-8. pubmed.ncbi.nlm.nih.gov
  6. Boellaard R, Delgado-Bolton R, Oyen WJG, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328-354. doi:10.1007/s00259-014-2961-x. pubmed.ncbi.nlm.nih.gov
  7. International Commission on Radiological Protection. Radiation Dose to Patients from Radiopharmaceuticals: A Compendium of Current Information Related to Frequently Used Substances. ICRP Publication 128. Ann ICRP. 2015;44(2 Suppl):7-321. icrp.org
  8. Mettler FA, Mahesh M, Bhargavan-Chatfield M, et al. Patient exposure from radiologic and nuclear medicine procedures in the United States: procedure volume and effective dose for the period 2006-2016. Radiology. 2020;295(2):418-427. doi:10.1148/radiol.2020192256. pubmed.ncbi.nlm.nih.gov
  9. Slart RHJA; Writing group; Reviewer group; et al. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group. Eur J Nucl Med Mol Imaging. 2018;45(7):1250-1269. pubmed.ncbi.nlm.nih.gov