Excerpt
Accurate identification and characterization of lymph node metastases (LNM) has important therapeutic and prognostic implications for most malignancies, with the site and number of involved LNs having a directive value on patient staging, treatment selection and planning, and eventual treatment outcomes [
1,
2]. Clinically, detection of LNMs relies on invasive biopsy procedures. A combination of
99mTc colloids and optical dye is typically used to guide SLN biopsy, followed by pathological assessment of the excised LNs [
3]. The success of this method relies on quantity and quality of biopsied LN samples and comprehensive microscopic inspections of entire LN volumes which is unrealistic and prone to inter-operator variability. Noninvasive imaging methods, primarily, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) are also used routinely in the clinic and are complementary to biopsy procedures [
4]. However, each method is fraught with its own set of limitations—structural imaging modalities such as MRI and CT rely on nodal size and morphology with limited sensitivity and specificity. The presence of necrosis on MRI is another commonly used indicator of LNMs. However, it suffers from inter-observer variability and demonstrates poor negative predictive value, particularly for non-enlarged and smaller nodes [
4]. Functional MRI methods that evaluate diffusion and perfusion suffer from drawbacks such as suboptimal signal-to-noise ratio and poor spatial resolution, which impacts both specificity and sensitivity of diagnoses. Dynamic contrast-enhanced (DCE) MRI that assesses vascularity has also demonstrated moderate success (72% sensitivity and 87% specificity) in LNM identification [
2]. Molecular imaging methods such as PET may overcome some of these challenges and provide substantially improved sensitivity and specificity over structural imaging modalities. [18F]FDG-PET is a widely used tool in PET imaging of sentinel LNs, demonstrating high sensitivity (~ 92–100%) and mixed specificity (77–93%), although recent reports have demonstrated limited specificity in differentiating LNMs from inflamed LNs [
1,
5]. However, the biggest challenge with PET imaging of LNMs lies in the limited spatial resolution: ~ 8–10 mm in conventional whole-body scanners and 4–5 mm in specially designed organ-specific scanners. Thus, it is somewhat unrealistic to rely on PET for detection of early LNMs, occult metastases, and extracapsular and extranodal extensions (ENE) within the LNs. Other targeted radiotracers such as [68 Ga]PSMA have also been used in LNM staging in prostate cancer, but non-specific uptake in adjacent ganglia was demonstrated to be a major pitfall [
1]. …
