The value of 18-FDG PET/CT as a supplemental screening method to overcome the challenges of dense breast imaging

Introduction: 1.To review the value of FDG PET/CT in detecting cancer of dense breasts.

2. To highlight FDG PET/CT dual time point’s (DTP) high sensitivity in assessing malignancies in breast, and its potential value as a screening method of dense breasts along discussing new approaches that can overcome FDG DTP’s limitations.

Methods: Multiple databases such as: Pub med, Google Scholar, etc. were used to gather a comprehensive literature search related to FDG PET/CT imaging in dense breasts.

Results: Dense breasts confer up to 6% higher risk of breast cancer. Digital mammograms, breast tomosynthesis, and ultrasound imaging are currently being used as annual screening methods for breast cancer. However, imaging dense breast can be difficult to interpret even by trained radiologists, which may result in malignancies involving micro-calcification to go undetected, Due to these difficulties, other methods, such as magnetic resonance imaging (MRI), and positron emission tomography (PET) have been evaluated to reduce rate of false negative findings. The evidence shows the utility of 18F-fluorodeoxyglucose (FDG) PET/CT in detecting and localizing metastases, restaging breast cancers, and evaluating therapeutic efficacy. FDG PET/CT of breast cancer can both characterize tumor biology and heterogeneity. Furthermore, it is highly sensitive in detecting axillary lymph node metastases and small tumors, but falters in sensitivity for in-situ carcinomas

The diagnostic and prognostic power of FDG PET/CT can be augmented by extracting metabolic glucose kinetic parameters using dynamic or dual-time-point (DTP) imaging. Glucose-6-phosphatase (G6P) is a particularly crucial enzyme that regulates efflux of glucose from the cell. The level of G6P expression has an important role in molecular profiling of cancer cells. Percentage change of SUV from first-time-point to second-time-point is a reliable imaging surrogate which correlates with function of this enzyme. The preliminary empirical data evaluating DTP FDG PET/CT accuracy in discerning between inflammatory and malignant lesions has shown promising results, however more studies are needed to corroborate these findings.

Furthermore, studies that show the relationship between 18F-FDG uptake and breast density have demonstrated that dense breasts have higher background 18- FDG uptake compared to normal breast tissues due to the presence of their characteristic microgranular tissues. This may obscure small hypermetabolic malignant nodules; however, delayed-time-point imaging could overcome this potential hurdle: FDG uptake decreases with time in normal breasts, whereas breast tissue composed of malignant cells accumulate FDG. . This contrast allows for detection and discrimination of lesions. Future research is needed to illuminate the benefits of DTP 18-FDG PET/CT in dense breasts and further support its utility as a supplemental screening tool.

Conclusions: Glucose metabolism alteration is a pivotal signature of malignant transformation, particularly in breast cancer. FDG PET/CT is the most accurate modality to quantify glucose metabolism, particularly using kinetic data or DTP imaging. While dense breasts hinder the diagnostic utility of structural imaging by obscuring morphological changes in early stages of the malignancy, molecular imaging has the potential to enhance the detectability and characterization by focusing on unique molecular and biochemical characteristics of malignant cells. Unparalleled sensitivity of PET imaging provides clinicians with a methodology to flow radiolabeled molecules at pico-molar concentration (1 mCi of 18F-FDG is equal to 0.58 pmol molecules). Total-body PET brings a new dimension to this phenomenal pico-molar resolution: temporal resolution. Dynamic total-body PET combines the exceptional molecular and temporal resolution. This emerging technology provides us with a unique situation to revisit diagnostic and preventive medical imaging paradigms.