What is the current definition, investigation lineup, and epidemiological etiology of the most common causes of morbidity and mortality worldwide, including the role of PET/CT (Positron Emission Tomography/Computed Tomography) according to recent Harrison guidelines?

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Last updated: September 21, 2025View editorial policy

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PET/CT Role in Diagnosis, Investigation, and Epidemiology of Common Diseases

PET/CT imaging has become a cornerstone of patient management in oncology, with established roles in diagnosis, staging, treatment response assessment, and detection of disease recurrence across various conditions that contribute to global morbidity and mortality. 1

Definition and Technical Aspects of PET/CT

PET/CT is an integrated imaging modality that combines:

  • A Positron Emission Tomography (PET) scanner that detects metabolic activity using radiopharmaceuticals (most commonly [18F]FDG)
  • A Computed Tomography (CT) scanner that provides anatomical information
  • A single, joined patient handling system (table) that allows sequential acquisition with the patient in the same position 1

The integration of these two modalities provides co-registered functional and anatomical information, significantly improving diagnostic accuracy compared to either modality alone.

Common Imaging Protocols

PET/CT examinations can cover various imaging ranges:

  • Whole-body imaging: From the top of the head through the feet
  • Torso imaging: Base of the skull to mid-thigh (covers most relevant portions in many oncological diseases)
  • Limited-area tumor imaging: For evaluation of tumor-related changes in a specific body region
  • Dedicated brain imaging: Can be combined with whole-body or torso imaging 1

CT components may include:

  • Low-dose CT: Performed only for attenuation correction and anatomical correlation
  • Diagnostic CT: With or without contrast agents, using higher X-ray doses 1

Epidemiological Context and Common Indications

PET/CT has established roles in diagnosing and managing conditions that contribute significantly to global morbidity and mortality:

Oncology (Leading Cause of Global Mortality)

  • Differentiation of benign from malignant lesions
  • Searching for unknown primary tumors
  • Staging known malignancies
  • Monitoring treatment response
  • Evaluating residual abnormalities post-treatment
  • Detecting tumor recurrence
  • Guiding biopsy and radiation therapy planning 1

The actual clinical use of PET/CT in oncology includes:

  • Lung cancer (26% of PET/CT scans)
  • Hematological malignancies (12%)
  • Gastrointestinal cancers (9%)
  • Head and neck cancers (4%)
  • Skin cancers (4%)
  • Gynecological cancers (8%) 1

Cardiovascular Disease

PET/CT is increasingly used in cardiovascular applications, potentially replacing myocardial scintigraphy in some settings 1. In prosthetic heart valve endocarditis, PET/CT has been incorporated into diagnostic criteria in the most recent ESC guidelines 1.

Infection and Inflammation

PET/CT has an increasingly relevant role in detecting:

  • Septic emboli and metastatic infections
  • Inflammation of unknown origin
  • Fever of unknown origin 1

Investigation Lineup and Diagnostic Approach

The optimal diagnostic approach using PET/CT involves:

Pre-scan Assessment

  1. Review of medical history:

    • Diagnosis (type of cancer and known sites if applicable)
    • Oncological history and relevant comorbidity
    • Infection/inflammation and diabetes mellitus
    • Recent medications (especially antidiabetics, corticosteroids, growth factors)
    • Previous imaging results 1
  2. Laboratory tests:

    • Serum glucose (critical for FDG studies)
    • Renal function (if contrast is planned)
    • Relevant tumor markers 1

Patient Preparation

  • Fasting for at least 4-6 hours
  • Blood glucose control (particularly important in diabetic patients)
  • Hydration and comfortable temperature to reduce brown fat uptake
  • Minimizing muscle activity before and after tracer injection 1

Standardized Interpretation Criteria

For consistent reporting and interpretation, standardized criteria have been developed:

  1. In oncology: The Deauville criteria (5-point scale) is commonly used for lymphoma assessment:

    • DS 1 = No uptake
    • DS 2 = ≤ mediastinal blood pool uptake
    • DS 3 = > mediastinal blood pool uptake, ≤ liver uptake
    • DS 4 = > liver uptake (at least 10% more)
    • DS 5 = >> liver uptake (at least twice) 1
  2. In plasma cell disorders: The IMPeTUs criteria evaluate:

    • Metabolic state of bone marrow
    • Number and site of focal lesions
    • Presence of paramedullary disease
    • Presence of extramedullary disease
    • Presence of fractures on CT 1
  3. In prosthetic valve endocarditis: PET/CT findings should be correlated with clinical and other diagnostic findings, ideally discussed in a multidisciplinary "Endocarditis Team" 1

Multidisciplinary Approach

The interpretation of PET/CT findings should be integrated with other clinical and diagnostic information. In complex cases like endocarditis, a multidisciplinary team approach is recommended, including:

  • Cardiologists
  • Cardiothoracic surgeons
  • Microbiologists/infectious disease specialists
  • Radiologists and nuclear medicine physicians 1

Pitfalls and Limitations

Important considerations to avoid misinterpretation:

  1. False positives:

    • Recent valve implantation (within 3 months)
    • Inadequate suppression of myocardial FDG uptake
    • Surgical adhesives
    • Recent cytokine administration
    • Inflammatory conditions 1
  2. False negatives:

    • Prolonged antibiotic therapy before imaging
    • Small lesions (partial volume effect)
    • Hyperglycemia affecting FDG uptake 1
  3. Technical considerations:

    • Standardized acquisition protocols are essential for quantitative assessment
    • Consistent reconstruction methods are needed for comparison between scans 1

Future Perspectives

PET/CT applications continue to evolve:

  • Therapy monitoring in immunotherapy
  • Assessment of treatment response in plasma cell disorders
  • Evaluation of antibiotic therapy effectiveness
  • Integration with other advanced imaging modalities 1

The field is rapidly evolving, with increasing evidence supporting the cost-effectiveness of PET/CT in specific clinical scenarios, such as investigation of persistent/recurrent neutropenic fever in high-risk hematology patients 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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